[18F]FDG dose de-escalation and shortened acquisition duration using total-body PET/CT in pediatric tumor imaging: a prospective pilot study

[18F]FDG dose de-escalation and shortened acquisition duration using total-body PET/CT in pediatric tumor imaging: a prospective pilot study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article [ 18 F]FDG dose de-escalation and shortened acquisition duration using total-body PET/CT in pediatric tumor imaging: a prospective pilot study Ying-Ying Hu, Lei Liu, Wanqi Chen, Si Tang, Zhijian Li, Weiguang Zhang, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2250727/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose To characterize the diagnostic performance of [ 18 F]FDG dose de-escalation with shortened acquisition times using total-body PET/CT in pediatric tumor imaging in terms of the subjective image quality and quantification of tracer uptake. Methods In this single-center prospective study, 31 pediatric oncology patients under 14 years old were enrolled and underwent total-body PET/CT using the uEXPLORER PET/CT scanner. All patients were randomly assigned to one of four [ 18 F]FDG dose groups: full-dose (3.7 MBq/kg), 1/2-dose (1.9 MBq/kg), 1/3-dose (1.2 MBq/kg), and 1/4-dose (0.9 MBq/kg). Images with a shortened acquisition time frame (20 min, 12 min, 10 min, 8 min, 6 min, 5 min, 4 min, 3 min, 2 min, 1.5 min, 1 min, and 0.5 min) were reconstructed for each study, with the 20-min images as controls for each dose group. Semiquantitative uptake metrics were assessed using region-of-interest (ROI) analysis of healthy liver and suspected lesions. The subjective analysis was performed using 5-point Likert scales. Suspected major lesions and microlesions were recorded, while 3-point Likert scales were used for diagnostic confidence. Results With shortened acquisition times, the liver maximum standard uptake value (SUV max ) and standard deviation (SD) increased in each dose group. The signal-to-noise ratio (SNR) was significantly reduced with shortened acquisition time, while the lesion SUV max and tumor-to-background ratio (TBR) showed no significant deviation. A decent subjective image quality score could be achieved in the full-, 1/2-, 1/3-, and 1/4-dose groups with at least 2-min, 4-min, 6-min, and 8-min acquisitions, respectively, where great overall image quality and brain delineation (scored 5.0) and superior organ boundaries and image noise (scored over 4.0) could be achieved, and all suspicious lesions found in 20-min images were detectable with high diagnostic confidence. Conclusions The regimen of full-dose [ 18 F] FDG with a 2-min scan, 1/2-dose with a 4-min scan, 1/3-dose with a 6-min scan, and 1/4-dose with an 8-min scan using total-body PET/CT can provide great image qualities, can maintain a desired diagnostic performance and is feasible for pediatric oncological clinical applications. Trial registration: ChiCTR2000036334. Registered 22 August 2020. Pediatric Oncology Total-body PET/CT [18F]FDG Low-dose Acquisition duration Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Positron emission tomography (PET) integrated with computed tomography (CT) (PET/CT) has played an important role in the diagnosis, staging, surveillance, and therapeutic evaluation in pediatric cancers, such as lymphoma, sarcoma, and Langerhans cell histiocytosis( 1 – 3 ). However, radiation exposure is of major concern in pediatric imaging( 4 – 6 ). Lowering the injected [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) dose for children reduces radiation exposure( 7 , 8 ) but inevitably compromises PET image quality. Optimizing the injected activity and acquisition duration, i.e., time-activity product (TAP), is a common way to mitigate degradation in image quality( 9 – 11 ). The activity of [ 18 F]FDG recommended for pediatric patients by the Society of Nuclear Medicine and Molecular Imaging is 3.7–5.2 MBq/kg for a body PET/CT scan( 2 ), which is 3.5–5.3 MBq/kg recommended by other major imaging societies from North America, Europe, and Japan ( 12 – 15 ). Several studies have reported an optimized FDG regimen of 2.0-5.3 MBq/kg (3 min/bed) using a conventional PET/CT with 15–30 cm axial field-of-view (AFOV)( 11 , 16 – 18 ). A recent study based on simulated low-dose regimens indicated that the pediatric PET tracer dose might be reduced down to 1.2 MBq/kg( 19 ). However, due to the scarcity of related studies, there is not adequate evidence for pediatric low-dose [ 18 F]FDG total-body PET/CT imaging( 14 ). With the ultrahigh sensitivity brought by an elongated AFOV of 194 cm, total-body PET/CT has provided image quality improvement and diagnostic insight broadening( 20 ), which indicates the feasibility of low-count PET images( 21 , 22 ). Our preliminary study simulated a low dose and showed that the effective dose of [ 18 F]FDG to pediatric patients could be reduced to 1/10-dose (0.37 MBq/kg) for 10 min/bed( 23 ). Total-body PET/CT with a half [ 18 F]FDG (1.85 MBq/kg) injection for children under 14 years old achieved great image quality where a fast scanning time of 1 min might be sufficient( 24 ). Herein, we hypothesized that different levels of reduced injected activity would correspondingly require a certain acquisition duration to maintain diagnostic sufficiency( 23 , 24 ). In this study, we aimed to characterize the diagnostic performance of [ 18 F]FDG dose de-escalation with shortened acquisition times using total-body PET/CT in pediatric tumor imaging in terms of the subjective image quality and quantification of tracer uptake. Materials And Methods Patients This single-center prospective pilot study was approved by the Institutional Review Board of Sun Yat-sen University Cancer Center. Written informed consent from each guardian of each patient was obtained. Thirty-one pediatric oncology patients in our centre from November 2020 to August 2021 who were PET/CT naïve were enrolled in this study. All patients were under 14 years old with body weight less than 60 kg, and their blood glucose levels were measured to ascertain glycemia (< 6.1 mmol/L). All patients’ diagnoses were confirmed by postoperative pathology or biopsy. The exclusion criteria for this study included the following: 1) inability to cooperate, 2) retention of [ 18 F]FDG at the injection site, 3) voluntary motion artefacts, or 4) waiting time more than 80 min after injection. Imaging protocol Participants scheduled for total-body PET scans were randomly assigned to one of four dose groups of [ 18 F]FDG: 3.7 MBq/kg, 1.9 MBq/kg, 1.2 MBq/kg, and 0.9 MBq/kg (full-dose, 1/2-dose, 1/3-dose, and 1/4-dose) with ALEA randomization software after fasting for 4–5 h. The list-mode PET data were acquired using a total-body PET/CT scanner with a 194-cm-long axial AFOV (uEXPLORER, United Imaging Healthcare, Shanghai, China) 64 ± 12 min after [ 18 F]FDG injection. Unenhanced low-dose CT (LDCT) scans of the whole body (tube current, 10–20 mA; voltage, 100–120 kV; rotation time, 0.3–0.5 s; pitch, 1.2125; collimation, 80 × 0.5 mm) with mean volumetric CT dose indexes (CTDIvol) ranging from 2 to 4 mGy were reconstructed in a 512 × 512 matrix for attenuation correction. Image Reconstruction The full-time PET (20 min) and the shortened duration PET images (12 min, 10 min, 8 min, 6 min, 5 min, 4 min, 3 min, 2 min, 1.5 min, 1 min, and 0.5 min) were reconstructed. All PET images were reconstructed using ordered subset expectation maximization (OSEM) (3 iterations, 20 subsets, matrix 256 × 256, voxel size 2.34 × 2.34 × 2.89 mm 3 , 3 mm Gaussian postfilter) with time-of-flight and point spread function modelling and all necessary corrections, including attenuation and scatter correction. All image evaluations were performed at a commercial medical image processing workstation (uWorkstation-MI, United Imaging Healthcare). Image analysis Objective Analysis Objective evaluation of image quality was performed by an experienced technician under the supervision of a nuclear medicine physician. A circular sphere with a diameter of 1.5 cm was drawn on a visually homogeneous area of the right liver lobe as the background, and the standard uptake value (SUV), SUV max , SUV mean , and standard deviation (SD) of the volume of interest (VOI) were calculated. The signal-to-noise ratio (SNR) of the liver was calculated as the ratio of the SUV mean to the SD in the observed region. A three-dimensional VOI was drawn around the tumor lesions with focally enhanced uptake in transaxial slices, where the diameter of the lesion was greatest on PET images, to ensure total containment of the lesion for the calculation of SUV. The VOI on the 20-min image of each patient was bookmarked and then propagated to the shortened acquisition group images using self-developed software in MATLAB (MathWorks, MA, USA). The tumor-to-background ratio (TBR) was defined by dividing the SUV max of the tumor to the SUV mean of the background. Subjective evaluation Ssubjective PET image quality was independently rated on a 5-point Likert scale by two nuclear medicine physicians (a junior physician with 1 year of experience and a senior physician with 15 years of experience) who were blinded to patient information. On disagreement, a third senior nuclear medicine physician with 16 years of experience was introduced to finalize the rating. The dataset of pediatric patients was randomized by Fisher-Yates shuffle. Each patient was assigned an ID to be deanonymized for further analysis. The reconstructed series of each study were randomly loaded and anonymized to facilitate the blind evaluation. Low-dose noncontract CT reconstruction served as an anatomic reference. A 5-point Likert scale was used to assess the image quality based on the following parameters: ( 1 ) noise level, ( 2 ) conspicuity of suspected malignant lesions, and ( 3 ) conspicuity of the liver, spleen, bone and brain margin. The visual scale for image quality consisted of grades 5 to 1 (see Supplementary Table 1). An overall score of 3 and above was considered to meet the clinical diagnostic needs, as a score of 3 indicates routine clinical image quality, i.e., that obtained by a conventional integrated PET/CT scanner in our center (Biograph mCT, Siemens Healthcare, Henkestr, Germany) with an axial FOV of 16.4 cm (acquisition time, 1.5–2.0 min/bed positions, 6–10/patient). Lesion detection and diagnostic confidence Lesion detectability was quantitatively assessed by the lesion detection rate (LDR). Two readers were blinded to the image reconstruction settings while evaluating the PET images. The detected lesions in the full-acquisition time (20 min) of each dose level served as the standard control for the other shortened duration groups. Major lesions were defined as [ 18 F]FDG-avid lesions with a longest diameter > 1.5 cm in axial view. Lesions ≤ 1.5 cm in diameter were considered microlesions. After blind lesion evaluation, previous medical history, along with fused PET/CT images, was subsequently provided to readers to evaluate the adequacy for clinical diagnosis. The readers graded their diagnostic confidence on a 3-point Likert scale: LOW (0, 50–75% confidence), MODERATE (1, 76–90% confidence), and HIGH (2, > 90% confidence). Statistical analysis The statistical analyses were performed using R version 4.3.2. The Kruskal–Wallis rank-sum test and Dunn’s post hoc test for multiple comparisons were applied for subjective image quality analyses of different groups. Paired t tests with Bonferroni correction were used to compare the quantitative measurements between different groups, and p < 0.05 was considered statistically significant. Results Patient characteristics A total of 31 pediatric patients (14 females and 17 males) were included with an age of 7.9 ± 3.6 years and a BMI of 16.4 ± 3.1 kg/m 2 (range, 11.3–21.3 kg/m 2 ). The characteristics of the patients are summarized in Table 1 . The pathological types of tumors included lymphoma (n = 15), sarcoma (n = 6), neuroblastoma (n = 5), nasopharyngeal carcinoma (n = 1), and others (n = 4). Thirty-nine percent of the patients were newly diagnosed and underwent PET/CT as an initial assessment, while the other 19 underwent PET/CT for posttreatment evaluation (9/19 were lymphoma patients). The injected [ 18 F]FDG doses of full-dose (n = 6), 1/2-dose (n = 10), 1/3-dose (n = 8), and 1/4-dose (n = 7) were 3.7 ± 0.1 MBq/kg, 1.9 ± 0.2 MBq/kg, 1.2 ± 0.1, and 0.9 ± 0.1 MBq/kg, respectively. Twenty-two patients had 34 suspected FDG-avid major lesions detected from all standard control images, and 56 microlesions were detected in 18 patients (Table 2 ). Table 1 Clinical characteristics of pediatric oncological patients who underwent total-body PET/CT in this study. Dose group All 1 1/2 1/3 1/4 N (%) Total: 31 31 6 (19) 10 (32) 8 (26) 7 (23) Sex (male to female) 1.2 2.0 1.5 0.3 2.5 Age 7.9 ± 3.6 6.3 ± 2.2 6.5 ± 3.2 8.4 ± 4.4 10.6 ± 2.9 Height (cm) 125.5 ± 25.4 117.3 ± 15.6 114.0 ± 23.9 128.6 ± 28.9 145.4 ± 20.7 Weight (kg) 27.1 ± 13.0 21.6 ± 7.4 21.1 ± 8.4 29.6 ± 15.3 37.6 ± 13.9 BSA (m 2 ) 1.0 ± 0.3 15.3 ± 1.2 0.8 ± 0.2 1.0 ± 0.4 1.2 ± 0.3 BMI (kg/cm 2 ) 16.4 ± 3.1 15.3 ± 1.2 16.3 ± 4.7 16.6 ± 2.1 17.1 ± 2.3 Injected dose per weight (MBq/kg) 1.8 ± 1.0 3.7 ± 0.1 1.9 ± 0.2 1.2 ± 0.1 0.9 ± 0.1 Injected dose (MBq) 45.1 ± 25.3 80.2 ± 27.4 39.7 ± 16.5 36.5 ± 20.0 32.8 ± 11.4 Waiting time (min) 64 ± 12 61.2 ± 7.6 72.7 ± 16.7 58.5 ± 4.2 60.6 ± 6.4 Treatment before PET/CT NO 12 (39) 3 (50) 6 (60) 2 (25) 1 (14) YES 19 (61) 3 (50) 4 (40) 6 (75) 6 (86) With detected major lesion NO 10 (32) 2 (33) 2 (20) 4 (50) 2 (29) YES 21 (68) 4 (67) 8 (80) 4 (50) 5 (71) Number of major lesions Total: 34 8 (24) 13 (38) 6 (17) 7 (21) SUV max of major lesion 1.7–52.7 1.7–17.1 1.7–22.3 2.1–52.7 2.1–11.6 With detected microlesion NO 13 (42) 3 (50) 4 (40) 4 (50) 2 (29) YES 18 (58) 3 (50) 6 (60) 4 (50) 5 (71) Number of microlesions Total: 56 7 (12) 13 (23) 11 (20) 25 (45) SUV max of microlesion 1.4–37.0 1.7–3.2 1.4–8.6 3.2–37.0 1.9–10.2 *All values are presented as the mean value ± SD, N (%), or range (minimum to maxima). Table 2 Characteristics of the major lesions and microlesions Dose group 1 1/2 1/3 1/4 SUV group ≤ 3 > 3 ≤ 3 > 3 ≤ 3 > 3 ≤ 3 > 3 Total: 34 N = 8 N = 13 N = 6 N = 7 Number of major lesions 3 (38) 5 (62) 3 (23) 10 (77) 2 (33) 4 (67) 3 (43) 4 (57) Total: 56 N = 7 N = 13 N = 11 N = 25 Number of microlesions 6 (86) 1 (14) 4 (31) 9 (69) 0 11 (100) 13 (52) 12 (48) Foci lymph node others lymph node others lymph node others lymph node others 2 (29) 5 (71) 7 (55) 6 (46) 5 (45) 6 (55) 21 (84) 4 (16) *All values are presented as N (%). Quantitative Measurement Of Image Quality The quantitative measurements of image quality, including the liver SUV max , SUV mean , SD, and SNR, are presented in Supplementary Table 2, and the lesion SUV max and TBR are reported in Supplementary Table 3. Liver SNRs decreased with the reduction of acquisition time from 20 min to 0.5 min in each dose group. The liver SNR in the full-dose group at 3 min was significantly higher than that in the full-dose group at 2 min (14.3 and 11.5, p = 0.007). In the 1/2-dose group, the SNR in the 1/2-dose group at 2 min was significantly higher than that at 1.5 min (9.4 and 8.0, p = 0.02). In the 1/3-dose group, the SNR at 3 min was significantly higher than that at 2 min (10.5 and 8.7, p = 0.002), and the SNR at 2 min was significantly higher than that at 1.5 min (8.7 and 7.3, p = 0.007). The SNR with 1.5 min acquisition time was significantly higher than that with 1 min acquisition time (all p < 0.05) in each dose group, and the SNR with 1 min acquisition time was significantly higher than that with 0.5 min acquisition time ( p = 0.03 for full-dose group, p < 0.001 for other dose groups). There were no significant differences between the other adjacent acquisition times for each dose group. The liver SUV mean and SD, as well as the lesion SUV max and TBR, were not significantly different among adjacent acquisition time groups in the same dose group. Measurements of 20-min images served as the reference standard. The standardized comparison of the quality metrics between the different shortened-acquisition times for each dose level is shown in Fig. 1 , and the trends of standardized lesion SUV max and TBR are summarized in Fig. 2 . The trend of liver indexes remained consistent, except for the significant differences that appeared between the 1-min and 30-s groups. The differences in lesion SUV max and TBR were not significant (all p > 0.05), which might indicate good maintenance in lesion conspicuity. Subjective Measurement Of Pet Image Quality Figure 3 shows the subjective scores of PET image quality for each reconstruction (details shown in Supplementary Table 4). Subjective Likert scores decreased with shortened acquisition times. The minimum acquisition durations to maintain 4- and 5-point scores in image quality in all four aspects (Supplementary Table 1) for the full-, 1/2-, 1/3-, and 1/4-dose groups were 2 min, 4 min, 6 min, and 8 min, respectively. Specifically, the overall quality of the MIP images of the full-dose group at 1.5 min, the 1/2-dose group at 3 min, the 1/3-dose group at 3 min, and the 1/4-dose group at 5 min had a mean score above 4. Organ boundaries and image noise of the full-dose group at 2 min, the 1/2-dose group at 4 min, the 1/3-dose group at 6 min, and the 1/4-dose group at 8 min all had a mean score above 4, and in most cases, it was above 4.5. Brain delineation in the full-dose group at 2 min, the 1/2-dose group at 4 min, the 1/3-dose group at 6 min, and the 1/4-dose group at 8 min had scores of 5 points. To achieve the 3-point recognizable organ boundaries, the acquisition time for the full-, 1/2-, 1/3-, and 1/4-dose groups required at least 1 min, 2 min, 3 min, and 4 min, respectively, while regular image noise (3 points) required 1 min, 2 min, 3 min, and 5 min, respectively, which is consistent with our previous simulated study (shown in Figure 7)(23). All the mean scores of the overall qualities of MIP images, organ boundaries and image noise were lower than 3 points at each dose level with 0.5 min of acquisition. Brain recognition required at least 0.5 min, 1 min, 1.5 min, and 2 min for recognizable qualities in dose groups from full- to 1/4-dose, respectively. Figure 4 shows images of patients from 4 different dose groups as well as lower-level images at lower acquisition times. Lesion Detection And Clinical Diagnostic Confidence Thirty-four major lesions and 56 microlesions (average diameter of 8 ± 2 mm) could be identified in the four groups. There were 11 (32%) in the lymph nodes and 23 in the other organs among the major lesions, while 35 (65%) microlesions were lymph nodes. Details of the lesions are summarized in Table 2 . All major lesions found in controls could be detected down to 1 min in the full-dose group, the 1/2-dose group, and the 1/3-dose group and 1.5 min in the 1/4-dose group, while all microlesions could be detected down to 1 min in the full-dose group, 2 min in the 1/2-dose group and the 1/3-dose group at and 3 min in the 1/4-dose group. The LDR and the score of clinical diagnosis confidence are shown in Fig. 5 (details shown in Supplementary Table 5). In the full-dose group at 1 min and the 1/2-dose group at 2 min, all low-uptake microlesions were detected. However, half (3/6) were missed in the full-dose group at 0.5 min, and 1 out of 4 was missed in the 1/2-dose group at 1 min, and 4/4 were missed in the 1/2-dose group at 0.5 min. No low-uptake microlesions were found in the 1/3-dose group. A total of 13/13, 11/13, 3/13, and 1/13 low-uptake microlesions were detected in in the 1/4-dose group at 3 min, 2 min, 1 min, and 0.5 min, respectively. Of 33 microlesions in the four groups with higher [ 18 F]FDG uptake (SUV max > 3), only 4 could not be accurately detected from the images with a 1 min acquisition time. Physicians further evaluated whether the PET images were qualified for clinical diagnosis. The full-dose group at 2 min, the 1/2-dose group at 4 min, the 1/3-dose group at 4 min, the 1/4-dose group at 5 min, and groups with longer acquisition times all obtained high diagnostic confidence. The fused PET/CT was provided with medical history to two readers, and diagnostic confidence was greatly improved. Figure 6 shows the MIP images and lesion detectability of a child with nasopharyngeal carcinoma from the 1/4-dose group. Discussion In this prospective pilot study, we recruited oncological patients aged from neonates to 14 years old and explored the image quality and lesion detectability with uEXPLORER. The optimized combination of administered [ 18 F]FDG activity and different acquisition durations was evaluated. Our results suggested that a full-dose FDG injection (3.7 MBq/kg) with a 2-min scan, a 1/2-dose (1.9 MBq/kg) with a 4-min scan, a 1/3-dose (1.2 MBq/kg) with a 6-min scan and a 1/4-dose (0.9 MBq/kg) with an 8-min scan were definitely feasible for clinical applications in pediatric patients. Optimizing [ 18 F]FDG dosage regimens is essential for pediatric nuclear medicine, with current guidelines recommending 3.5–5.3 MBq/kg. Elongated axial FOV length allows the reduction of acquisition duration and injected [ 18 F]FDG activity for pediatric patients. Previous studies have revealed that the 1/4-dose was feasible for clinical diagnosis( 23 ). In the current study, we demonstrated that a full-dose at 2 min, a 1/2-dose at 4 min, a 1/3-dose at 6 min and a 1/4-dose group at 8 min could serve as novel clinical references for total-body PET/CT imaging. Such cases could achieve adequate image quality that is significantly superior to the conventional PET scanner with full lesion detectability and high diagnostic confidence even when using PET images alone. Several studies have validated the clinical advantages of total-body PET/CT in adults. An ultralow dose (0.37–0.45 MBq/kg) provides acceptable image quality for adult patients with malignancies( 25 , 26 ), and a 0.5–1 minute acquisition time has been found to be sufficient for clinical diagnosis with fast scanning( 27 ). Total-body PET/CT with half-dose FDG in lung cancer could obtain an equivalent image quality compared to conventional PET/CT with an acquisition time of 2 minutes( 28 ). Pediatric patients need to be separately evaluated due to their distinctive physiological characteristics( 22 ). With the development of new PET technology, including PET/MR, the pediatric [ 18 F]FDG dose could be reduced to 1.5–1.8 MBq/kg using scanners with AFOV of 25.0–25.8 cm( 17 , 19 , 29 ). A few investigations have explored dose- and time-dependent optimization with total-body PET/CT in children, most of which used simulated low-count images. The recommendation in this study was consistent with our previous simulation studies (see Fig. 7 )( 23 ) and our retrospective study( 24 ). Considering that some older children were similar to adults in size( 15 , 30 ), we only included children under 14 years old. However, it is well known that lower doses are more beneficial to infants, and it is also noteworthy that 61% of the children in our study were posttreatment or under clinical follow-up who could require more scans, with 10 out of 31 patients having no FDG-avid lesions. For those numerous patients, an ultralow [ 18 F]FDG dose seems to be more urgently required and needs to be evaluated separately in the future. The estimated effective doses of [ 18 F]FDG injected activity using total-body PET to acquire an optimal image ranged from 0.37 0.74 MBq/kg. Overall, our study demonstrated that total-body PET images alone with a reduction in dose could be applied. However, the radiation dose depends on both the administered dose of [ 18 F]FDG and CT, which suggests that CT is also a safety concern, and further exploration of the reduction in CT dose along with [ 18 F]FDG dose is needed. The PET acquisition time is determined by the injected radiotracer dose and the sensitivity of the PET scanner( 2 ). It is possible to compensate for the lower radiation dose with a longer scan duration per bed, especially in pediatric imaging. For conventional systems, acquisition times are generally 1–3 minutes with bed overlaps for each bed position and corresponding adjustments to injected activity( 14 ). For pediatric PET/MR (with 25 cm ~ 32 cm AFOV), 2.5 MBq/kg for a 3 min/bed position is recommended( 14 , 17 , 19 , 29 ). The total acquisition time, however, might still be long for children and result in noncooperation and motion artefacts, which might lead to insufficient image quality or interruption of the PET scan, potentially necessitating a repeat study( 2 , 13 , 31 ). Reduction of acquisition time leads to fewer motion artefacts and thus less need for sedation and could greatly improve pediatric comfort and image quality. The total-body PET covers the entire body of the patient in one bed position, which has great potential to shorten the total PET acquisition time( 22 , 27 ). A scanner with 194-cm-long AFOV, however, might bring discomfort to patients with claustrophobia. Therefore, the acquisition duration could be further reduced. For adults, it was recommended that a regular total-body PET scan was 0.5–2 min with full dose (3.7 MBq/kg) and 3–5 min with a low dose (1.85 MBq/kg)( 22 ). A 1-min fast scan with a full dose injected was adequate for oncological imaging in adults( 32 ). For patients with low body weight, e.g., infants and toddlers, a shorter exam duration was more beneficial than reduced injected activity( 33 ). Our previous study suggested that theoretically, a TAP of 3.7 MBq/kg·min/bed (1 bed per total-body imaging) would be recommended for a routine pediatric protocol, and a half dose of [ 18 F]FDG could maintain a comparable image quality to a conventional PET scanner at a fast scanning time of 1 min( 23 , 24 ). This study aimed for routine clinical application with a margin of safety and validated and further complemented previous conclusions. Image quality is the premise and the detection of lesions is the key in the evaluation of diagnostic performance. The LDR is strongly related to the image texture, size, shape, and surrounding environment as well as the readers’ experience( 34 , 35 ). Microlesions with low metabolism or low contrast were often ignored with low dose and reduced time due to unsatisfactory image noise. False-negative findings, however, were presented, especially with fast scans and in the low-contrast microlesions, which was consistent with earlier studies( 23 , 27 ). The limitations are as follows. First, this is a single-center study with a limited sample size. Second, the extrapolation of this study is limited, i.e., restricted to uEXPLORER PET systems. Third, subgroup analyses, including tumour subtypes, clinical purposes, age, and BMI, were limited by sample size and therefore were not performed. The dose- and time-dependent effects on lesion shape, volume, contrast, and delayed imaging warrant further investigation. Last, limited by ethical issues, the reduced-dose groups lack full-dose studies for intrapatient comparison. Conclusions Our study demonstrated that a full-dose [ 18 F]FDG injection (3.7 MBq/kg) with a 2-min scan, a 1/2 dose (1.9 MBq/kg) with a 4-min scan, a 1/3 dose (1.2 MBq/kg) with a 6-min scan and a 1/4 dose (0.9 MBq/kg) with an 8-min scan were definitely feasible for clinical applications in pediatric patients, which provides sufficient image quality comparable to conventional PET/CT, perfect lesion conspicuity and high diagnostic confidence. Declarations Funding : The authors did not receive financial support from any organization for the submitted work. Conflicts of interest/Competing interests : Authors Jiatai Feng, Hongyan Sun, and Runze Wu are employees of United Imaging Research. The other authors working at Sun-Yat sen University Cancer Center have full control of the data and declare that they have no conflicts of interest. Availability of data and material : The datasets generated and/or analysed during the current study are available from the corresponding author upon reasonable request. Code availability : The code applied and/or analysed during the current study is available from the corresponding author upon reasonable request. Author contributions : Conceptualization: Yingying Hu, Yumo Zhao, Wei Fan; Methodology: Yingying Hu, Lei Liu, Zhijian Li; Formal analysis and investigation: Yingying Hu, Lei Liu, Wanqi Chen, Si Tang; Writing - original draft preparation: Lei Liu, Wanqi Chen, Yumo Zhao; Writing - review and editing: Lei Liu, Si Tang, Yumo Zhao, Yingying Hu, Xu Zhang, Runze Wu; Technical support: Weiguang Zhang, Jiatai Feng, Runze Wu, Hong Yan Sun; Resources: Yingying Hu, Fan Wei; Supervision: Fan Wei, Yumo Zhao, Yingying Hu. All authors read and approved the final manuscript. Ethics approval : All procedures performed in studies involving human participants were conducted in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Consent to participate : Informed consent was obtained from the legal guardians. Consent for publication : Additional informed consent was obtained from all legal guardians for whom identifying information is included in this article. Acknowledgements : Not applicable. References Uslu L, Donig J, Link M, Rosenberg J, Quon A, Daldrup-Link HE. Value of 18F-FDG PET and PET/CT for evaluation of pediatric malignancies. J Nucl Med. 2015;56(2):274–86. Vali R, Alessio A, Balza R, Borgwardt L, Bar-Sever Z, Czachowski M, et al. SNMMI Procedure Standard/EANM Practice Guideline on Pediatric (18)F-FDG PET/CT for Oncology 1.0. J Nucl Med. 2021;62(1):99–110. 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Radiation exposure and mortality risk from CT and PET imaging of patients with malignant lymphoma. Eur Radiol. 2012;22(9):1946–54. Xie T, Zaidi H. Evaluation of radiation dose to anthropomorphic paediatric models from positron-emitting labelled tracers. Phys Med Biol. 2014;59(5):1165–87. Fahey FH, Treves ST, Adelstein SJ. Minimizing and communicating radiation risk in pediatric nuclear medicine. J Nucl Med. 2011;52(8):1240–51. Chawla SC, Federman N, Zhang D, Nagata K, Nuthakki S, McNitt-Gray M, et al. Estimated cumulative radiation dose from PET/CT in children with malignancies: a 5-year retrospective review. Pediatr Radiol. 2010;40(5):681–6. Alessio AM, Sammer M, Phillips GS, Manchanda V, Mohr BC, Parisi MT. Evaluation of optimal acquisition duration or injected activity for pediatric 18F-FDG PET/CT. J Nucl Med. 2011;52(7):1028–34. Fahey FH, Goodkind AB, Plyku D, Khamwan K, O'Reilly SE, Cao X, et al. Dose Estimation in Pediatric Nuclear Medicine. Semin Nucl Med. 2017;47(2):118–25. Parisi MT, Bermo MS, Alessio AM, Sharp SE, Gelfand MJ, Shulkin BL. Optimization of Pediatric PET/CT. Semin Nucl Med. 2017;47(3):258–74. Dickson J, Eberlein U, Lassmann M. The effect of modern PET technology and techniques on the EANM paediatric dosage card. Eur J Nucl Med Mol Imaging. 2022;49(6):1964–9. Alessio AM, Kinahan PE, Manchanda V, Ghioni V, Aldape L, Parisi MT. Weight-based, low-dose pediatric whole-body PET/CT protocols. J Nucl Med. 2009;50(10):1570–7. Accorsi R, Karp JS, Surti S. Improved dose regimen in pediatric PET. J Nucl Med. 2010;51(2):293–300. Gatidis S, Schmidt H, la Fougere C, Nikolaou K, Schwenzer NF, Schafer JF. Defining optimal tracer activities in pediatric oncologic whole-body (18)F-FDG-PET/MRI. Eur J Nucl Med Mol Imaging. 2016;43(13):2283–9. Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42(2):328–54. Schmall JP, Surti S, Otero HJ, Servaes S, Karp JS, States LJ. Investigating Low-Dose Image Quality in Whole-Body Pediatric (18)F-FDG Scans Using Time-of-Flight PET/MRI. J Nucl Med. 2021;62(1):123–30. Badawi RD, Shi H, Hu P, Chen S, Xu T, Price PM, et al. First Human Imaging Studies with the EXPLORER Total-Body PET Scanner. J Nucl Med. 2019;60(3):299–303. Spencer BA, Berg E, Schmall JP, Omidvari N, Leung EK, Abdelhafez YG, et al. Performance Evaluation of the uEXPLORER Total-Body PET/CT Scanner Based on NEMA NU 2-2018 with Additional Tests to Characterize PET Scanners with a Long Axial Field of View. J Nucl Med. 2021;62(6):861–70. Yu H, Gu Y, Fan W, Gao Y, Wang M, Zhu X, et al. Expert consensus on oncological [(18)F]FDG total-body PET/CT imaging (version 1). Eur Radiol. 2022. Zhao YM, Li YH, Chen T, Zhang WG, Wang LH, Feng J, et al. Image quality and lesion detectability in low-dose pediatric (18)F-FDG scans using total-body PET/CT. Eur J Nucl Med Mol Imaging. 2021;48(11):3378–85. Chen W, Liu L, Li Y, Li S, Li Z, Zhang W, et al. Evaluation of pediatric malignancies using total-body PET/CT with half-dose [(18)F]-FDG. Eur J Nucl Med Mol Imaging. 2022. Tan H, Cai D, Sui X, Qi C, Mao W, Zhang Y, et al. Investigating ultra-low-dose total-body [18F]-FDG PET/CT in colorectal cancer: initial experience. Eur J Nucl Med Mol Imaging. 2022;49(3):1002–11. Hu Y, Liu G, Yu H, Wang Y, Li C, Tan H, et al. Feasibility of Acquisitions Using Total-Body PET/CT with an Ultra-Low (18)F-FDG Activity. J Nucl Med. 2022;63(6):959–65. Hu P, Zhang Y, Yu H, Chen S, Tan H, Qi C, et al. Total-body (18)F-FDG PET/CT scan in oncology patients: how fast could it be? Eur J Nucl Med Mol Imaging. 2021;48(8):2384–94. Tan H, Sui X, Yin H, Yu H, Gu Y, Chen S, et al. Total-body PET/CT using half-dose FDG and compared with conventional PET/CT using full-dose FDG in lung cancer. Eur J Nucl Med Mol Imaging. 2021;48(6):1966–75. Zucchetta P, Branchini M, Zorz A, Bodanza V, Cecchin D, Paiusco M, et al. Quantitative analysis of image metrics for reduced and standard dose pediatric (18)F-FDG PET/MRI examinations. Br J Radiol. 2019;92(1095):20180438. Masuda Y, Kondo C, Matsuo Y, Uetani M, Kusakabe K. Comparison of imaging protocols for 18F-FDG PET/CT in overweight patients: optimizing scan duration versus administered dose. J Nucl Med. 2009;50(6):844–8. Shammas A, Lim R, Charron M. Pediatric FDG PET/CT: physiologic uptake, normal variants, and benign conditions. Radiographics. 2009;29(5):1467–86. Zhang YQ, Hu PC, Wu RZ, Gu YS, Chen SG, Yu HJ, et al. The image quality, lesion detectability, and acquisition time of (18)F-FDG total-body PET/CT in oncological patients. Eur J Nucl Med Mol Imaging. 2020;47(11):2507–15. Reichkendler M, Andersen FL, Borgwardt L, Nygaard U, Albrecht-Beste E, Andersen KF, et al. Long axial field of view with 5 min acquisition time enables PET/CT in toddler without sedation. J Nucl Med. 2022. Xu L, Li RS, Wu RZ, Yang R, You QQ, Yao XC, et al. Small lesion depiction and quantification accuracy of oncological (18)F-FDG PET/CT with small voxel and Bayesian penalized likelihood reconstruction. EJNMMI Phys. 2022;9(1):23. van der Vos CS, Koopman D, Rijnsdorp S, Arends AJ, Boellaard R, van Dalen JA, et al. Quantification, improvement, and harmonization of small lesion detection with state-of-the-art PET. Eur J Nucl Med Mol Imaging. 2017;44(Suppl 1):4–16. Supplementary Files supplementary.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2250727","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":155371015,"identity":"68ecde33-001e-4111-a5b9-665699204841","order_by":0,"name":"Ying-Ying Hu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYBACAxDxgWQtjDNI1sLMQ5IWc4kcM2mbP4ftDY4ffsDwcU8tA//sBvxaLGcAteS2HU7ccCbNgHHGs+MMEncOEHDYDZCWhsMJBjd4gC48cIzBQCKBCC0WIIeRpoWB7TDjBoiWGiK0nHlWbNnblp44E+iXgzMOHOCRuEFIy/HkjTd+/LG25zt++OGDDwfq5PhnENDCwMBhIsHA0AxmHmBgOExMHLE/BqaXOhivDp/SUTAKRsEoGKEAAGe4RWiVzubdAAAAAElFTkSuQmCC","orcid":"","institution":"Sun Yat-sen University Cancer Center","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Ying-Ying","middleName":"","lastName":"Hu","suffix":""},{"id":155371016,"identity":"affd4141-26f4-4e5c-a4be-9f37e9b41f18","order_by":1,"name":"Lei Liu","email":"","orcid":"","institution":"Sun Yat-sen University Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Liu","suffix":""},{"id":155371017,"identity":"01eac380-5d55-4453-b215-42aa0ab74d30","order_by":2,"name":"Wanqi Chen","email":"","orcid":"","institution":"Sun Yat-sen University Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wanqi","middleName":"","lastName":"Chen","suffix":""},{"id":155371018,"identity":"5c9cab05-e04d-45b1-97ce-89cec798d494","order_by":3,"name":"Si Tang","email":"","orcid":"","institution":"Sun Yat-sen University Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Si","middleName":"","lastName":"Tang","suffix":""},{"id":155371019,"identity":"34824f6e-600b-4747-a16e-330ebb0806a4","order_by":4,"name":"Zhijian Li","email":"","orcid":"","institution":"Sun Yat-sen University Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhijian","middleName":"","lastName":"Li","suffix":""},{"id":155371020,"identity":"5518735c-9a5b-4a63-8bb2-4d7734a77798","order_by":5,"name":"Weiguang Zhang","email":"","orcid":"","institution":"Sun Yat-sen University Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Weiguang","middleName":"","lastName":"Zhang","suffix":""},{"id":155371021,"identity":"2c5c8e81-dafa-4583-a52a-e343ed7b5237","order_by":6,"name":"Xu Zhang","email":"","orcid":"","institution":"Sun Yat-sen University Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xu","middleName":"","lastName":"Zhang","suffix":""},{"id":155371022,"identity":"3bf8ad4d-784b-498a-b74f-e3d16c7cc605","order_by":7,"name":"Jiatai Feng","email":"","orcid":"","institution":"united imaging healthcare","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jiatai","middleName":"","lastName":"Feng","suffix":""},{"id":155371023,"identity":"2235758e-d7bf-4257-89ed-62274b36e559","order_by":8,"name":"Hongyan Sun","email":"","orcid":"","institution":"united imaging healthcare","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hongyan","middleName":"","lastName":"Sun","suffix":""},{"id":155371024,"identity":"5d4ab2dc-f0c7-41b3-a4a2-28894f6816a0","order_by":9,"name":"Runze Wu","email":"","orcid":"","institution":"united imaging healthcare","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Runze","middleName":"","lastName":"Wu","suffix":""},{"id":155371025,"identity":"badb8b52-ffb9-4883-a032-949b49fe33fd","order_by":10,"name":"Fan Wei","email":"","orcid":"","institution":"Sun Yat-sen University Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fan","middleName":"","lastName":"Wei","suffix":""},{"id":155371026,"identity":"1ecc2d85-3186-449c-ad32-2c56ac504cdb","order_by":11,"name":"Yumo Zhao","email":"","orcid":"","institution":"Sun Yat-sen University Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yumo","middleName":"","lastName":"Zhao","suffix":""}],"badges":[],"createdAt":"2022-11-08 11:07:41","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2250727/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2250727/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":29690533,"identity":"fd51c597-686e-4baa-81ee-7ea553db99b0","added_by":"auto","created_at":"2022-11-29 23:41:29","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":760883,"visible":true,"origin":"","legend":"\u003cp\u003eThe comparison of the objective image quality parameters in total-body PET/CT images by FDG dose and acquisition time reduction. Scatterplots of the standardized liver signal-to-noise ratio (SNR) (a), SUV\u003csub\u003emax \u003c/sub\u003e(b), SUV\u003csub\u003emean \u003c/sub\u003e(c) and SD (d). A 20-min image for each dose group was used as a reference, and the standardized value was equal to the value of the other acquisition time subgroups divided by the reference.\u003c/p\u003e\n\u003cp\u003e*indicates \u003cem\u003ep\u003c/em\u003e\u0026lt;0.05, **indicates \u003cem\u003ep\u003c/em\u003e\u0026lt;0.01, and ***indicates \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001.\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2250727/v1/9f3720caff41012df506efb9.jpg"},{"id":29690534,"identity":"15973314-f231-4076-9f69-188ab714c579","added_by":"auto","created_at":"2022-11-29 23:41:29","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":461011,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of the objective image quality parameters in total-body PET/CT images by FDG dose and acquisition time reduction. Scatterplots of the (a) standardized tumour-to-background ratio (TBR) were calculated by dividing the SUV\u003csub\u003emax\u003c/sub\u003e of the lesion by the liver SUV\u003csub\u003emean\u003c/sub\u003e and (b) the lesion SUV\u003csub\u003emax\u003c/sub\u003e. A 20-min image for each dose group was used as a reference, and the standardized value was equal to the value of the other acquisition time subgroups divided by the reference.\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2250727/v1/cba24dd1659e4d4edfc8e239.jpg"},{"id":29691093,"identity":"d2b6c3e4-4a5c-44de-9b87-45cc870f3ad4","added_by":"auto","created_at":"2022-11-29 23:49:29","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":306388,"visible":true,"origin":"","legend":"\u003cp\u003eSubjective image quality was assessed by a 5-point Likert scale.\u003c/p\u003e\n\u003cp\u003e*Dark blue, mean score = 5.0; Light blue, mean score = 4.0; Grey, mean score = 3.0, regular quality of daily practice; White, mean score \u0026lt; 3.0.\u003c/p\u003e\n\u003cp\u003e*20~1 indicate 20~1-min acquisition time, while 0.5 indicates 30-s acquisition time.\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2250727/v1/b91ac5ccdc664338b471c929.jpg"},{"id":29690538,"identity":"827e35f6-f7bc-48a6-9d0f-8f03cf5f1139","added_by":"auto","created_at":"2022-11-29 23:41:29","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":929021,"visible":true,"origin":"","legend":"\u003cp\u003eThe axial images of the full-, 1/2-, 1/3-, and 1/4-dose groups generated by reduced acquisition times. The 20-minute images showing the liver, spleen, and lumbar spine were of perfect quality. The lowest duration for organ boundaries and image noise scores of 3 in these 4 patients (from full- to 1-4-dose group) was 20 min, 8 min, 6 min, 4 min, 2 min, 1.5 min, 1 min, and 0.5 min, respectively.\u003c/p\u003e\n\u003cp\u003e*All images were reconstructed with a voxel size of 2.34 × 2.34 × 2.89 mm\u003csup\u003e3\u003c/sup\u003e.\u003c/p\u003e","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2250727/v1/ddfa83f9eabb058606d39f9a.jpg"},{"id":29691798,"identity":"af8073e4-79c6-4e3d-a041-3885d54c9e21","added_by":"auto","created_at":"2022-11-29 23:57:29","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":347478,"visible":true,"origin":"","legend":"\u003cp\u003eLesion detectability and diagnostic confidence were assessed by a 3-point Likert scale.\u003c/p\u003e\n\u003cp\u003e*Dark blue, 100% of lesions detected or high diagnostic confidence (i.e., \u0026gt;90% confidence) with mean score = 2.0.\u003c/p\u003e\n\u003cp\u003e*20~1 indicate 20~1-min acquisition time, while 0.5 indicates 30-s acquisition time.\u003c/p\u003e","description":"","filename":"Fig5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2250727/v1/1ed43f4f938b2344b521aa3b.jpg"},{"id":29691092,"identity":"eb1c91c1-83f9-4485-bce1-3a0afc48e5ba","added_by":"auto","created_at":"2022-11-29 23:49:29","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1443371,"visible":true,"origin":"","legend":"\u003cp\u003eA 13-year-old boy diagnosed with nasopharyngeal carcinoma with 0.85 MBq/kg (1/4-dose) [\u003csup\u003e18\u003c/sup\u003eF]FDG injection. The maximum intensity projection (MIP) and axial images showing the avid FDG lesions were identified in the serial dose reduction image generated by reduced acquisition times. The overall image score of the 20-min images was 5, while the scores from 6 min to 0.5 min were 5, 4, 4, 3, 3, 2, 2 and 1 points, respectively. The major lesion in the nasopharynx (red arrow) was identifiable at an acquisition time of 1 min, while the microlesion (a lymph node) in the left neck was missed down to 2 min (blue arrow).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;*\u003c/strong\u003eAll images were reconstructed with a voxel size of 2.34 × 2.34 × 2.89 mm\u003csup\u003e3\u003c/sup\u003e.\u003c/p\u003e","description":"","filename":"Fig6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2250727/v1/f1491c96570a2baffbf87ba5.jpg"},{"id":29690536,"identity":"9d168d0f-fb03-47d3-8fa2-c7bc028da2c4","added_by":"auto","created_at":"2022-11-29 23:41:29","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":294630,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Fig7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2250727/v1/ead0ee254806e5baa088afa3.jpg"},{"id":30675363,"identity":"9b1f9a8e-bb03-453a-8b59-f5c082ea0026","added_by":"auto","created_at":"2022-12-22 14:29:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":838935,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2250727/v1/c56b0091-1116-4900-89f2-3b27ab3c026b.pdf"},{"id":29690540,"identity":"a0b405f8-208d-44c9-a94d-6bd57b3ed7c7","added_by":"auto","created_at":"2022-11-29 23:41:29","extension":"docx","order_by":11,"title":"","display":"","copyAsset":false,"role":"supplement","size":77440,"visible":true,"origin":"","legend":"","description":"","filename":"supplementary.docx","url":"https://assets-eu.researchsquare.com/files/rs-2250727/v1/244da65d55f04851c8fdb8ca.docx"}],"financialInterests":"","formattedTitle":"\u003cp\u003e[\u003csup\u003e18\u003c/sup\u003eF]FDG dose de-escalation and shortened acquisition duration using total-body PET/CT in pediatric tumor imaging: a prospective pilot study\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePositron emission tomography (PET) integrated with computed tomography (CT) (PET/CT) has played an important role in the diagnosis, staging, surveillance, and therapeutic evaluation in pediatric cancers, such as lymphoma, sarcoma, and Langerhans cell histiocytosis(\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). However, radiation exposure is of major concern in pediatric imaging(\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Lowering the injected [\u003csup\u003e18\u003c/sup\u003eF]fluorodeoxyglucose ([\u003csup\u003e18\u003c/sup\u003eF]FDG) dose for children reduces radiation exposure(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) but inevitably compromises PET image quality. Optimizing the injected activity and acquisition duration, i.e., time-activity product (TAP), is a common way to mitigate degradation in image quality(\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe activity of [\u003csup\u003e18\u003c/sup\u003eF]FDG recommended for pediatric patients by the Society of Nuclear Medicine and Molecular Imaging is 3.7\u0026ndash;5.2 MBq/kg for a body PET/CT scan(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), which is 3.5\u0026ndash;5.3 MBq/kg recommended by other major imaging societies from North America, Europe, and Japan (\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Several studies have reported an optimized FDG regimen of 2.0-5.3 MBq/kg (3 min/bed) using a conventional PET/CT with 15\u0026ndash;30 cm axial field-of-view (AFOV)(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). A recent study based on simulated low-dose regimens indicated that the pediatric PET tracer dose might be reduced down to 1.2 MBq/kg(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). However, due to the scarcity of related studies, there is not adequate evidence for pediatric low-dose [\u003csup\u003e18\u003c/sup\u003eF]FDG total-body PET/CT imaging(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWith the ultrahigh sensitivity brought by an elongated AFOV of 194 cm, total-body PET/CT has provided image quality improvement and diagnostic insight broadening(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), which indicates the feasibility of low-count PET images(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Our preliminary study simulated a low dose and showed that the effective dose of [\u003csup\u003e18\u003c/sup\u003eF]FDG to pediatric patients could be reduced to 1/10-dose (0.37 MBq/kg) for 10 min/bed(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Total-body PET/CT with a half [\u003csup\u003e18\u003c/sup\u003eF]FDG (1.85 MBq/kg) injection for children under 14 years old achieved great image quality where a fast scanning time of 1 min might be sufficient(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHerein, we hypothesized that different levels of reduced injected activity would correspondingly require a certain acquisition duration to maintain diagnostic sufficiency(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). In this study, we aimed to characterize the diagnostic performance of [\u003csup\u003e18\u003c/sup\u003eF]FDG dose de-escalation with shortened acquisition times using total-body PET/CT in pediatric tumor imaging in terms of the subjective image quality and quantification of tracer uptake.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003ch3\u003ePatients\u003c/h3\u003e\n\u003cp\u003eThis single-center prospective pilot study was approved by the Institutional Review Board of Sun Yat-sen University Cancer Center. Written informed consent from each guardian of each patient was obtained. Thirty-one pediatric oncology patients in our centre from November 2020 to August 2021 who were PET/CT na\u0026iuml;ve were enrolled in this study. All patients were under 14 years old with body weight less than 60 kg, and their blood glucose levels were measured to ascertain glycemia (\u0026lt;\u0026thinsp;6.1 mmol/L). All patients\u0026rsquo; diagnoses were confirmed by postoperative pathology or biopsy. The exclusion criteria for this study included the following: 1) inability to cooperate, 2) retention of [\u003csup\u003e18\u003c/sup\u003eF]FDG at the injection site, 3) voluntary motion artefacts, or 4) waiting time more than 80 min after injection.\u003c/p\u003e\n\u003ch3\u003eImaging protocol\u003c/h3\u003e\n\u003cp\u003eParticipants scheduled for total-body PET scans were randomly assigned to one of four dose groups of [\u003csup\u003e18\u003c/sup\u003eF]FDG: 3.7 MBq/kg, 1.9 MBq/kg, 1.2 MBq/kg, and 0.9 MBq/kg (full-dose, 1/2-dose, 1/3-dose, and 1/4-dose) with ALEA randomization software after fasting for 4\u0026ndash;5 h. The list-mode PET data were acquired using a total-body PET/CT scanner with a 194-cm-long axial AFOV (uEXPLORER, United Imaging Healthcare, Shanghai, China) 64\u0026thinsp;\u0026plusmn;\u0026thinsp;12 min after [\u003csup\u003e18\u003c/sup\u003eF]FDG injection. Unenhanced low-dose CT (LDCT) scans of the whole body (tube current, 10\u0026ndash;20 mA; voltage, 100\u0026ndash;120 kV; rotation time, 0.3\u0026ndash;0.5 s; pitch, 1.2125; collimation, 80 \u0026times; 0.5 mm) with mean volumetric CT dose indexes (CTDIvol) ranging from 2 to 4 mGy were reconstructed in a 512 \u0026times; 512 matrix for attenuation correction.\u003c/p\u003e\n\u003ch3\u003eImage Reconstruction\u003c/h3\u003e\n\u003cp\u003eThe full-time PET (20 min) and the shortened duration PET images (12 min, 10 min, 8 min, 6 min, 5 min, 4 min, 3 min, 2 min, 1.5 min, 1 min, and 0.5 min) were reconstructed. All PET images were reconstructed using ordered subset expectation maximization (OSEM) (3 iterations, 20 subsets, matrix 256 \u0026times; 256, voxel size 2.34 \u0026times; 2.34 \u0026times; 2.89 mm\u003csup\u003e3\u003c/sup\u003e, 3 mm Gaussian postfilter) with time-of-flight and point spread function modelling and all necessary corrections, including attenuation and scatter correction. All image evaluations were performed at a commercial medical image processing workstation (uWorkstation-MI, United Imaging Healthcare).\u003c/p\u003e\n\u003ch3\u003eImage analysis\u003c/h3\u003e\n\u003ch3\u003eObjective Analysis\u003c/h3\u003e\n\u003cp\u003eObjective evaluation of image quality was performed by an experienced technician under the supervision of a nuclear medicine physician. A circular sphere with a diameter of 1.5 cm was drawn on a visually homogeneous area of the right liver lobe as the background, and the standard uptake value (SUV), SUV\u003csub\u003emax\u003c/sub\u003e, SUV\u003csub\u003emean\u003c/sub\u003e, and standard deviation (SD) of the volume of interest (VOI) were calculated. The signal-to-noise ratio (SNR) of the liver was calculated as the ratio of the SUV\u003csub\u003emean\u003c/sub\u003e to the SD in the observed region.\u003c/p\u003e\n\u003cp\u003eA three-dimensional VOI was drawn around the tumor lesions with focally enhanced uptake in transaxial slices, where the diameter of the lesion was greatest on PET images, to ensure total containment of the lesion for the calculation of SUV. The VOI on the 20-min image of each patient was bookmarked and then propagated to the shortened acquisition group images using self-developed software in MATLAB (MathWorks, MA, USA). The tumor-to-background ratio (TBR) was defined by dividing the SUV\u003csub\u003emax\u003c/sub\u003e of the tumor to the SUV\u003csub\u003emean\u003c/sub\u003e of the background.\u003c/p\u003e\n\u003ch3\u003eSubjective evaluation\u003c/h3\u003e\n\u003cp\u003eSsubjective PET image quality was independently rated on a 5-point Likert scale by two nuclear medicine physicians (a junior physician with 1 year of experience and a senior physician with 15 years of experience) who were blinded to patient information. On disagreement, a third senior nuclear medicine physician with 16 years of experience was introduced to finalize the rating. The dataset of pediatric patients was randomized by Fisher-Yates shuffle. Each patient was assigned an ID to be deanonymized for further analysis. The reconstructed series of each study were randomly loaded and anonymized to facilitate the blind evaluation. Low-dose noncontract CT reconstruction served as an anatomic reference. A 5-point Likert scale was used to assess the image quality based on the following parameters: (\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e) noise level, (\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e) conspicuity of suspected malignant lesions, and (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e) conspicuity of the liver, spleen, bone and brain margin. The visual scale for image quality consisted of grades 5 to 1 (see Supplementary Table\u0026nbsp;1). An overall score of 3 and above was considered to meet the clinical diagnostic needs, as a score of 3 indicates routine clinical image quality, i.e., that obtained by a conventional integrated PET/CT scanner in our center (Biograph mCT, Siemens Healthcare, Henkestr, Germany) with an axial FOV of 16.4 cm (acquisition time, 1.5\u0026ndash;2.0 min/bed positions, 6\u0026ndash;10/patient).\u003c/p\u003e\n\u003ch3\u003eLesion detection and diagnostic confidence\u003c/h3\u003e\n\u003cp\u003eLesion detectability was quantitatively assessed by the lesion detection rate (LDR). Two readers were blinded to the image reconstruction settings while evaluating the PET images. The detected lesions in the full-acquisition time (20 min) of each dose level served as the standard control for the other shortened duration groups. Major lesions were defined as [\u003csup\u003e18\u003c/sup\u003eF]FDG-avid lesions with a longest diameter\u0026thinsp;\u0026gt;\u0026thinsp;1.5 cm in axial view. Lesions\u0026thinsp;\u0026le;\u0026thinsp;1.5 cm in diameter were considered microlesions. After blind lesion evaluation, previous medical history, along with fused PET/CT images, was subsequently provided to readers to evaluate the adequacy for clinical diagnosis. The readers graded their diagnostic confidence on a 3-point Likert scale: LOW (0, 50\u0026ndash;75% confidence), MODERATE (1, 76\u0026ndash;90% confidence), and HIGH (2, \u0026gt;\u0026thinsp;90% confidence).\u003c/p\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch3\u003eStatistical analysis\u003c/h3\u003e\n\u003cp\u003eThe statistical analyses were performed using R version 4.3.2. The Kruskal\u0026ndash;Wallis rank-sum test and Dunn\u0026rsquo;s post hoc test for multiple comparisons were applied for subjective image quality analyses of different groups. Paired \u003cem\u003et\u003c/em\u003e tests with Bonferroni correction were used to compare the quantitative measurements between different groups, and \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/em\u003e was considered statistically significant.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n\u003ch3\u003ePatient characteristics\u003c/h3\u003e\n\u003cp\u003eA total of 31 pediatric patients (14 females and 17 males) were included with an age of 7.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6 years and a BMI of 16.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1 kg/m\u003csup\u003e2\u003c/sup\u003e (range, 11.3\u0026ndash;21.3 kg/m\u003csup\u003e2\u003c/sup\u003e). The characteristics of the patients are summarized in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The pathological types of tumors included lymphoma (n\u0026thinsp;=\u0026thinsp;15), sarcoma (n\u0026thinsp;=\u0026thinsp;6), neuroblastoma (n\u0026thinsp;=\u0026thinsp;5), nasopharyngeal carcinoma (n\u0026thinsp;=\u0026thinsp;1), and others (n\u0026thinsp;=\u0026thinsp;4). Thirty-nine percent of the patients were newly diagnosed and underwent PET/CT as an initial assessment, while the other 19 underwent PET/CT for posttreatment evaluation (9/19 were lymphoma patients). The injected [\u003csup\u003e18\u003c/sup\u003eF]FDG doses of full-dose (n\u0026thinsp;=\u0026thinsp;6), 1/2-dose (n\u0026thinsp;=\u0026thinsp;10), 1/3-dose (n\u0026thinsp;=\u0026thinsp;8), and 1/4-dose (n\u0026thinsp;=\u0026thinsp;7) were 3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1 MBq/kg, 1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2 MBq/kg, 1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1, and 0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1 MBq/kg, respectively. Twenty-two patients had 34 suspected FDG-avid major lesions detected from all standard control images, and 56 microlesions were detected in 18 patients (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eClinical characteristics of pediatric oncological patients who underwent total-body PET/CT in this study.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDose group\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAll\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e1/2\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e1/3\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e1/4\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eN (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal: 31\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (19)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (32)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (26)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (23)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSex (male to female)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.5\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHeight (cm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e125.5\u0026thinsp;\u0026plusmn;\u0026thinsp;25.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e117.3\u0026thinsp;\u0026plusmn;\u0026thinsp;15.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e114.0\u0026thinsp;\u0026plusmn;\u0026thinsp;23.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e128.6\u0026thinsp;\u0026plusmn;\u0026thinsp;28.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e145.4\u0026thinsp;\u0026plusmn;\u0026thinsp;20.7\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWeight (kg)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27.1\u0026thinsp;\u0026plusmn;\u0026thinsp;13.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29.6\u0026thinsp;\u0026plusmn;\u0026thinsp;15.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37.6\u0026thinsp;\u0026plusmn;\u0026thinsp;13.9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBSA (m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI (kg/cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInjected dose per weight (MBq/kg)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInjected dose (MBq)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45.1\u0026thinsp;\u0026plusmn;\u0026thinsp;25.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e80.2\u0026thinsp;\u0026plusmn;\u0026thinsp;27.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39.7\u0026thinsp;\u0026plusmn;\u0026thinsp;16.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36.5\u0026thinsp;\u0026plusmn;\u0026thinsp;20.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32.8\u0026thinsp;\u0026plusmn;\u0026thinsp;11.4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWaiting time (min)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e64\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e61.2\u0026thinsp;\u0026plusmn;\u0026thinsp;7.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e72.7\u0026thinsp;\u0026plusmn;\u0026thinsp;16.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e58.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTreatment before PET/CT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNO\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12 (39)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (60)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (25)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (14)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYES\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19 (61)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (40)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (75)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (86)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eWith detected major lesion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNO\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (32)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (33)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (20)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (29)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYES\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21 (68)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (67)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (80)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (71)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNumber of major lesions\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal: 34\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (24)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13 (38)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (17)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (21)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSUV\u003csub\u003emax\u003c/sub\u003e of major lesion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.7\u0026ndash;52.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.7\u0026ndash;17.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.7\u0026ndash;22.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.1\u0026ndash;52.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.1\u0026ndash;11.6\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eWith detected microlesion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNO\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13 (42)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (40)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (29)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYES\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18 (58)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (60)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (71)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNumber of microlesions\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal: 56\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (12)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13 (23)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (20)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25 (45)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSUV\u003csub\u003emax\u003c/sub\u003e of microlesion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.4\u0026ndash;37.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.7\u0026ndash;3.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.4\u0026ndash;8.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.2\u0026ndash;37.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.9\u0026ndash;10.2\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"7\"\u003e*All values are presented as the mean value\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, N (%), or range (minimum to maxima).\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eCharacteristics of the major lesions and microlesions\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDose group\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1/2\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1/3\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1/4\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSUV group\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026le;\u0026thinsp;3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026le;\u0026thinsp;3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026le;\u0026thinsp;3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026le;\u0026thinsp;3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal: 34\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;7\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNumber of major lesions\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (38)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (62)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (23)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (77)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (33)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (67)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (43)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (57)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal: 56\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;25\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNumber of microlesions\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (86)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (14)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (31)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (69)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (100)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13 (52)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12 (48)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eFoci\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003elymph node\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eothers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003elymph node\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eothers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003elymph node\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eothers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003elymph node\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eothers\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (29)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (71)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (55)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (46)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (45)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (55)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21 (84)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (16)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"10\"\u003e*All values are presented as N (%).\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003ch3\u003eQuantitative Measurement Of Image Quality\u003c/h3\u003e\n\u003cp\u003eThe quantitative measurements of image quality, including the liver SUV\u003csub\u003emax\u003c/sub\u003e, SUV\u003csub\u003emean\u003c/sub\u003e, SD, and SNR, are presented in Supplementary Table\u0026nbsp;2, and the lesion SUV\u003csub\u003emax\u003c/sub\u003e and TBR are reported in Supplementary Table\u0026nbsp;3. Liver SNRs decreased with the reduction of acquisition time from 20 min to 0.5 min in each dose group. The liver SNR in the full-dose group at 3 min was significantly higher than that in the full-dose group at 2 min (14.3 and 11.5, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007). In the 1/2-dose group, the SNR in the 1/2-dose group at 2 min was significantly higher than that at 1.5 min (9.4 and 8.0, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02). In the 1/3-dose group, the SNR at 3 min was significantly higher than that at 2 min (10.5 and 8.7, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), and the SNR at 2 min was significantly higher than that at 1.5 min (8.7 and 7.3, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007). The SNR with 1.5 min acquisition time was significantly higher than that with 1 min acquisition time (all \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in each dose group, and the SNR with 1 min acquisition time was significantly higher than that with 0.5 min acquisition time (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03 for full-dose group, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for other dose groups). There were no significant differences between the other adjacent acquisition times for each dose group. The liver SUV\u003csub\u003emean\u003c/sub\u003e and SD, as well as the lesion SUV\u003csub\u003emax\u003c/sub\u003e and TBR, were not significantly different among adjacent acquisition time groups in the same dose group.\u003c/p\u003e\n\u003cp\u003eMeasurements of 20-min images served as the reference standard. The standardized comparison of the quality metrics between the different shortened-acquisition times for each dose level is shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, and the trends of standardized lesion SUV\u003csub\u003emax\u003c/sub\u003e and TBR are summarized in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. The trend of liver indexes remained consistent, except for the significant differences that appeared between the 1-min and 30-s groups. The differences in lesion SUV\u003csub\u003emax\u003c/sub\u003e and TBR were not significant (all \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), which might indicate good maintenance in lesion conspicuity.\u003c/p\u003e\n\u003ch3\u003eSubjective Measurement Of Pet Image Quality\u003c/h3\u003e\n\u003cp\u003eFigure 3 shows the subjective scores of PET image quality for each reconstruction (details shown in Supplementary Table 4). Subjective Likert scores decreased with shortened acquisition times. The minimum acquisition durations to maintain 4- and 5-point scores in image quality in all four aspects (Supplementary Table 1) for the full-, 1/2-, 1/3-, and 1/4-dose groups were 2 min, 4 min, 6 min, and 8 min, respectively. Specifically, the overall quality of the MIP images of the full-dose group at 1.5 min, the 1/2-dose group at 3 min, the 1/3-dose group at 3 min, and the 1/4-dose group at 5 min had a mean score above 4. Organ boundaries and image noise of the full-dose group at 2 min, the 1/2-dose group at 4 min, the 1/3-dose group at 6 min, and the 1/4-dose group at 8 min all had a mean score above 4, and in most cases, it was above 4.5. Brain delineation in the full-dose group at 2 min, the 1/2-dose group at 4 min, the 1/3-dose group at 6 min, and the 1/4-dose group at 8 min had scores of 5 points. To achieve the 3-point recognizable organ boundaries, the acquisition time for the full-, 1/2-, 1/3-, and 1/4-dose groups required at least 1 min, 2 min, 3 min, and 4 min, respectively, while regular image noise (3 points) required 1 min, 2 min, 3 min, and 5 min, respectively, which is consistent with our previous simulated study (shown in Figure 7)(23). All the mean scores of the overall qualities of MIP images, organ boundaries and image noise were lower than 3 points at each dose level with 0.5 min of acquisition. Brain recognition required at least 0.5 min, 1 min, 1.5 min, and 2 min for recognizable qualities in dose groups from full- to 1/4-dose, respectively. Figure 4 shows images of patients from 4 different dose groups as well as lower-level images at lower acquisition times.\u003c/p\u003e\n\u003ch3\u003eLesion Detection And Clinical Diagnostic Confidence\u003c/h3\u003e\n\u003cp\u003eThirty-four major lesions and 56 microlesions (average diameter of 8\u0026thinsp;\u0026plusmn;\u0026thinsp;2 mm) could be identified in the four groups. There were 11 (32%) in the lymph nodes and 23 in the other organs among the major lesions, while 35 (65%) microlesions were lymph nodes. Details of the lesions are summarized in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. All major lesions found in controls could be detected down to 1 min in the full-dose group, the 1/2-dose group, and the 1/3-dose group and 1.5 min in the 1/4-dose group, while all microlesions could be detected down to 1 min in the full-dose group, 2 min in the 1/2-dose group and the 1/3-dose group at and 3 min in the 1/4-dose group. The LDR and the score of clinical diagnosis confidence are shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e (details shown in Supplementary Table\u0026nbsp;5). In the full-dose group at 1 min and the 1/2-dose group at 2 min, all low-uptake microlesions were detected. However, half (3/6) were missed in the full-dose group at 0.5 min, and 1 out of 4 was missed in the 1/2-dose group at 1 min, and 4/4 were missed in the 1/2-dose group at 0.5 min. No low-uptake microlesions were found in the 1/3-dose group. A total of 13/13, 11/13, 3/13, and 1/13 low-uptake microlesions were detected in in the 1/4-dose group at 3 min, 2 min, 1 min, and 0.5 min, respectively. Of 33 microlesions in the four groups with higher [\u003csup\u003e18\u003c/sup\u003eF]FDG uptake (SUV\u003csub\u003emax\u003c/sub\u003e \u0026gt; 3), only 4 could not be accurately detected from the images with a 1 min acquisition time.\u003c/p\u003e\n\u003cp\u003ePhysicians further evaluated whether the PET images were qualified for clinical diagnosis. The full-dose group at 2 min, the 1/2-dose group at 4 min, the 1/3-dose group at 4 min, the 1/4-dose group at 5 min, and groups with longer acquisition times all obtained high diagnostic confidence. The fused PET/CT was provided with medical history to two readers, and diagnostic confidence was greatly improved. Figure\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e shows the MIP images and lesion detectability of a child with nasopharyngeal carcinoma from the 1/4-dose group.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this prospective pilot study, we recruited oncological patients aged from neonates to 14 years old and explored the image quality and lesion detectability with uEXPLORER. The optimized combination of administered [\u003csup\u003e18\u003c/sup\u003eF]FDG activity and different acquisition durations was evaluated. Our results suggested that a full-dose FDG injection (3.7 MBq/kg) with a 2-min scan, a 1/2-dose (1.9 MBq/kg) with a 4-min scan, a 1/3-dose (1.2 MBq/kg) with a 6-min scan and a 1/4-dose (0.9 MBq/kg) with an 8-min scan were definitely feasible for clinical applications in pediatric patients.\u003c/p\u003e \u003cp\u003eOptimizing [\u003csup\u003e18\u003c/sup\u003eF]FDG dosage regimens is essential for pediatric nuclear medicine, with current guidelines recommending 3.5\u0026ndash;5.3 MBq/kg. Elongated axial FOV length allows the reduction of acquisition duration and injected [\u003csup\u003e18\u003c/sup\u003eF]FDG activity for pediatric patients. Previous studies have revealed that the 1/4-dose was feasible for clinical diagnosis(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). In the current study, we demonstrated that a full-dose at 2 min, a 1/2-dose at 4 min, a 1/3-dose at 6 min and a 1/4-dose group at 8 min could serve as novel clinical references for total-body PET/CT imaging. Such cases could achieve adequate image quality that is significantly superior to the conventional PET scanner with full lesion detectability and high diagnostic confidence even when using PET images alone. Several studies have validated the clinical advantages of total-body PET/CT in adults. An ultralow dose (0.37\u0026ndash;0.45 MBq/kg) provides acceptable image quality for adult patients with malignancies(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e), and a 0.5\u0026ndash;1 minute acquisition time has been found to be sufficient for clinical diagnosis with fast scanning(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Total-body PET/CT with half-dose FDG in lung cancer could obtain an equivalent image quality compared to conventional PET/CT with an acquisition time of 2 minutes(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Pediatric patients need to be separately evaluated due to their distinctive physiological characteristics(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). With the development of new PET technology, including PET/MR, the pediatric [\u003csup\u003e18\u003c/sup\u003eF]FDG dose could be reduced to 1.5\u0026ndash;1.8 MBq/kg using scanners with AFOV of 25.0\u0026ndash;25.8 cm(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). A few investigations have explored dose- and time-dependent optimization with total-body PET/CT in children, most of which used simulated low-count images. The recommendation in this study was consistent with our previous simulation studies (see Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e7\u003c/span\u003e)(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) and our retrospective study(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Considering that some older children were similar to adults in size(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e), we only included children under 14 years old. However, it is well known that lower doses are more beneficial to infants, and it is also noteworthy that 61% of the children in our study were posttreatment or under clinical follow-up who could require more scans, with 10 out of 31 patients having no FDG-avid lesions. For those numerous patients, an ultralow [\u003csup\u003e18\u003c/sup\u003eF]FDG dose seems to be more urgently required and needs to be evaluated separately in the future. The estimated effective doses of [\u003csup\u003e18\u003c/sup\u003eF]FDG injected activity using total-body PET to acquire an optimal image ranged from 0.37 0.74 MBq/kg. Overall, our study demonstrated that total-body PET images alone with a reduction in dose could be applied. However, the radiation dose depends on both the administered dose of [\u003csup\u003e18\u003c/sup\u003eF]FDG and CT, which suggests that CT is also a safety concern, and further exploration of the reduction in CT dose along with [\u003csup\u003e18\u003c/sup\u003eF]FDG dose is needed.\u003c/p\u003e \u003cp\u003eThe PET acquisition time is determined by the injected radiotracer dose and the sensitivity of the PET scanner(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). It is possible to compensate for the lower radiation dose with a longer scan duration per bed, especially in pediatric imaging. For conventional systems, acquisition times are generally 1\u0026ndash;3 minutes with bed overlaps for each bed position and corresponding adjustments to injected activity(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). For pediatric PET/MR (with 25 cm\u0026thinsp;~\u0026thinsp;32 cm AFOV), 2.5 MBq/kg for a 3 min/bed position is recommended(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). The total acquisition time, however, might still be long for children and result in noncooperation and motion artefacts, which might lead to insufficient image quality or interruption of the PET scan, potentially necessitating a repeat study(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Reduction of acquisition time leads to fewer motion artefacts and thus less need for sedation and could greatly improve pediatric comfort and image quality. The total-body PET covers the entire body of the patient in one bed position, which has great potential to shorten the total PET acquisition time(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). A scanner with 194-cm-long AFOV, however, might bring discomfort to patients with claustrophobia. Therefore, the acquisition duration could be further reduced. For adults, it was recommended that a regular total-body PET scan was 0.5\u0026ndash;2 min with full dose (3.7 MBq/kg) and 3\u0026ndash;5 min with a low dose (1.85 MBq/kg)(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). A 1-min fast scan with a full dose injected was adequate for oncological imaging in adults(\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). For patients with low body weight, e.g., infants and toddlers, a shorter exam duration was more beneficial than reduced injected activity(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Our previous study suggested that theoretically, a TAP of 3.7 MBq/kg\u0026middot;min/bed (1 bed per total-body imaging) would be recommended for a routine pediatric protocol, and a half dose of [\u003csup\u003e18\u003c/sup\u003eF]FDG could maintain a comparable image quality to a conventional PET scanner at a fast scanning time of 1 min(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). This study aimed for routine clinical application with a margin of safety and validated and further complemented previous conclusions.\u003c/p\u003e \u003cp\u003eImage quality is the premise and the detection of lesions is the key in the evaluation of diagnostic performance. The LDR is strongly related to the image texture, size, shape, and surrounding environment as well as the readers\u0026rsquo; experience(\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). Microlesions with low metabolism or low contrast were often ignored with low dose and reduced time due to unsatisfactory image noise. False-negative findings, however, were presented, especially with fast scans and in the low-contrast microlesions, which was consistent with earlier studies(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe limitations are as follows. First, this is a single-center study with a limited sample size. Second, the extrapolation of this study is limited, i.e., restricted to uEXPLORER PET systems. Third, subgroup analyses, including tumour subtypes, clinical purposes, age, and BMI, were limited by sample size and therefore were not performed. The dose- and time-dependent effects on lesion shape, volume, contrast, and delayed imaging warrant further investigation. Last, limited by ethical issues, the reduced-dose groups lack full-dose studies for intrapatient comparison.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur study demonstrated that a full-dose [\u003csup\u003e18\u003c/sup\u003eF]FDG injection (3.7 MBq/kg) with a 2-min scan, a 1/2 dose (1.9 MBq/kg) with a 4-min scan, a 1/3 dose (1.2 MBq/kg) with a 6-min scan and a 1/4 dose (0.9 MBq/kg) with an 8-min scan were definitely feasible for clinical applications in pediatric patients, which provides sufficient image quality comparable to conventional PET/CT, perfect lesion conspicuity and high diagnostic confidence.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: The authors did not receive financial support from any organization for the submitted work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest/Competing interests\u003c/strong\u003e: Authors Jiatai Feng, Hongyan Sun, and Runze Wu are employees of United Imaging Research. The other authors working at Sun-Yat sen University Cancer Center have full control of the data and declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e: The datasets generated and/or analysed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode availability\u003c/strong\u003e: The code applied and/or analysed during the current study is available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e:\u0026nbsp;Conceptualization: Yingying Hu, Yumo Zhao, Wei Fan; Methodology: Yingying Hu, Lei Liu, Zhijian Li; Formal analysis and investigation: Yingying Hu, Lei Liu, Wanqi Chen, Si Tang; Writing - original draft preparation: Lei Liu, Wanqi Chen, Yumo Zhao; Writing - review and editing: Lei Liu, Si Tang, Yumo Zhao, Yingying Hu, Xu Zhang, Runze Wu; Technical support: Weiguang Zhang, Jiatai Feng, Runze Wu, Hong Yan Sun; Resources: Yingying Hu, Fan Wei; Supervision: Fan Wei, Yumo Zhao, Yingying Hu. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e: All procedures performed in studies involving human participants were conducted in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e: Informed consent was obtained from the legal guardians.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Additional informed consent was obtained from all legal guardians for whom identifying information is included in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e: Not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eUslu L, Donig J, Link M, Rosenberg J, Quon A, Daldrup-Link HE. 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Investigating Low-Dose Image Quality in Whole-Body Pediatric (18)F-FDG Scans Using Time-of-Flight PET/MRI. J Nucl Med. 2021;62(1):123\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBadawi RD, Shi H, Hu P, Chen S, Xu T, Price PM, et al. First Human Imaging Studies with the EXPLORER Total-Body PET Scanner. J Nucl Med. 2019;60(3):299\u0026ndash;303.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpencer BA, Berg E, Schmall JP, Omidvari N, Leung EK, Abdelhafez YG, et al. Performance Evaluation of the uEXPLORER Total-Body PET/CT Scanner Based on NEMA NU 2-2018 with Additional Tests to Characterize PET Scanners with a Long Axial Field of View. J Nucl Med. 2021;62(6):861\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYu H, Gu Y, Fan W, Gao Y, Wang M, Zhu X, et al. Expert consensus on oncological [(18)F]FDG total-body PET/CT imaging (version 1). Eur Radiol. 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao YM, Li YH, Chen T, Zhang WG, Wang LH, Feng J, et al. Image quality and lesion detectability in low-dose pediatric (18)F-FDG scans using total-body PET/CT. Eur J Nucl Med Mol Imaging. 2021;48(11):3378\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen W, Liu L, Li Y, Li S, Li Z, Zhang W, et al. Evaluation of pediatric malignancies using total-body PET/CT with half-dose [(18)F]-FDG. Eur J Nucl Med Mol Imaging. 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTan H, Cai D, Sui X, Qi C, Mao W, Zhang Y, et al. Investigating ultra-low-dose total-body [18F]-FDG PET/CT in colorectal cancer: initial experience. Eur J Nucl Med Mol Imaging. 2022;49(3):1002\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu Y, Liu G, Yu H, Wang Y, Li C, Tan H, et al. Feasibility of Acquisitions Using Total-Body PET/CT with an Ultra-Low (18)F-FDG Activity. J Nucl Med. 2022;63(6):959\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu P, Zhang Y, Yu H, Chen S, Tan H, Qi C, et al. Total-body (18)F-FDG PET/CT scan in oncology patients: how fast could it be? Eur J Nucl Med Mol Imaging. 2021;48(8):2384\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTan H, Sui X, Yin H, Yu H, Gu Y, Chen S, et al. Total-body PET/CT using half-dose FDG and compared with conventional PET/CT using full-dose FDG in lung cancer. Eur J Nucl Med Mol Imaging. 2021;48(6):1966\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZucchetta P, Branchini M, Zorz A, Bodanza V, Cecchin D, Paiusco M, et al. Quantitative analysis of image metrics for reduced and standard dose pediatric (18)F-FDG PET/MRI examinations. Br J Radiol. 2019;92(1095):20180438.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMasuda Y, Kondo C, Matsuo Y, Uetani M, Kusakabe K. Comparison of imaging protocols for 18F-FDG PET/CT in overweight patients: optimizing scan duration versus administered dose. J Nucl Med. 2009;50(6):844\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShammas A, Lim R, Charron M. Pediatric FDG PET/CT: physiologic uptake, normal variants, and benign conditions. Radiographics. 2009;29(5):1467\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang YQ, Hu PC, Wu RZ, Gu YS, Chen SG, Yu HJ, et al. The image quality, lesion detectability, and acquisition time of (18)F-FDG total-body PET/CT in oncological patients. Eur J Nucl Med Mol Imaging. 2020;47(11):2507\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReichkendler M, Andersen FL, Borgwardt L, Nygaard U, Albrecht-Beste E, Andersen KF, et al. Long axial field of view with 5 min acquisition time enables PET/CT in toddler without sedation. J Nucl Med. 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu L, Li RS, Wu RZ, Yang R, You QQ, Yao XC, et al. Small lesion depiction and quantification accuracy of oncological (18)F-FDG PET/CT with small voxel and Bayesian penalized likelihood reconstruction. EJNMMI Phys. 2022;9(1):23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan der Vos CS, Koopman D, Rijnsdorp S, Arends AJ, Boellaard R, van Dalen JA, et al. Quantification, improvement, and harmonization of small lesion detection with state-of-the-art PET. Eur J Nucl Med Mol Imaging. 2017;44(Suppl 1):4\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Pediatric, Oncology, Total-body PET/CT, [18F]FDG, Low-dose, Acquisition duration","lastPublishedDoi":"10.21203/rs.3.rs-2250727/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2250727/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\n\u003cp\u003eTo characterize the diagnostic performance of [\u003csup\u003e18\u003c/sup\u003eF]FDG dose de-escalation with shortened acquisition times using total-body PET/CT in pediatric tumor imaging in terms of the subjective image quality and quantification of tracer uptake.\u003c/p\u003e\n\u003ch2\u003eMethods\u003c/h2\u003e\n\u003cp\u003eIn this single-center prospective study, 31 pediatric oncology patients under 14 years old were enrolled and underwent total-body PET/CT using the uEXPLORER PET/CT scanner. All patients were randomly assigned to one of four [\u003csup\u003e18\u003c/sup\u003eF]FDG dose groups: full-dose (3.7 MBq/kg), 1/2-dose (1.9 MBq/kg), 1/3-dose (1.2 MBq/kg), and 1/4-dose (0.9 MBq/kg). Images with a shortened acquisition time frame (20 min, 12 min, 10 min, 8 min, 6 min, 5 min, 4 min, 3 min, 2 min, 1.5 min, 1 min, and 0.5 min) were reconstructed for each study, with the 20-min images as controls for each dose group. Semiquantitative uptake metrics were assessed using region-of-interest (ROI) analysis of healthy liver and suspected lesions. The subjective analysis was performed using 5-point Likert scales. Suspected major lesions and microlesions were recorded, while 3-point Likert scales were used for diagnostic confidence.\u003c/p\u003e\n\u003ch2\u003eResults\u003c/h2\u003e\n\u003cp\u003eWith shortened acquisition times, the liver maximum standard uptake value (SUV\u003csub\u003emax\u003c/sub\u003e) and standard deviation (SD) increased in each dose group. The signal-to-noise ratio (SNR) was significantly reduced with shortened acquisition time, while the lesion SUV\u003csub\u003emax\u003c/sub\u003e and tumor-to-background ratio (TBR) showed no significant deviation. A decent subjective image quality score could be achieved in the full-, 1/2-, 1/3-, and 1/4-dose groups with at least 2-min, 4-min, 6-min, and 8-min acquisitions, respectively, where great overall image quality and brain delineation (scored 5.0) and superior organ boundaries and image noise (scored over 4.0) could be achieved, and all suspicious lesions found in 20-min images were detectable with high diagnostic confidence.\u003c/p\u003e\n\u003ch2\u003eConclusions\u003c/h2\u003e\n\u003cp\u003eThe regimen of full-dose [\u003csup\u003e18\u003c/sup\u003eF] FDG with a 2-min scan, 1/2-dose with a 4-min scan, 1/3-dose with a 6-min scan, and 1/4-dose with an 8-min scan using total-body PET/CT can provide great image qualities, can maintain a desired diagnostic performance and is feasible for pediatric oncological clinical applications.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTrial registration: ChiCTR2000036334. Registered 22 August 2020.\u003c/em\u003e\u003c/p\u003e","manuscriptTitle":"[18F]FDG dose de-escalation and shortened acquisition duration using total-body PET/CT in pediatric tumor imaging: a prospective pilot study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-11-29 23:41:24","doi":"10.21203/rs.3.rs-2250727/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"477266f5-52e8-4ee7-accf-b2556c58b3e5","owner":[],"postedDate":"November 29th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-12-22T14:29:32+00:00","versionOfRecord":[],"versionCreatedAt":"2022-11-29 23:41:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2250727","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2250727","identity":"rs-2250727","version":["v1"]},"buildId":"rHA-KDH7Qsr4HCuvH75dn","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}