Prospective Comparison of 68Ga-DOTA-IBA, 99mTc-MDP Scintigraphy, and Multidetector CT for Skeletal Metastases

Prospective Comparison of 68Ga-DOTA-IBA, 99mTc-MDP Scintigraphy, and Multidetector CT for Skeletal Metastases | 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 Prospective Comparison of 68Ga-DOTA-IBA, 99mTc-MDP Scintigraphy, and Multidetector CT for Skeletal Metastases Xinyi Lin, Na Zhang, Rongliang Wang, Huajun Liu, Wei Wang, Tingting Xu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6656119/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 Objective : This prospective study was to evaluate the diagnostic efficacy of 68 Ga-labeled DOTA-ibandronic acid positron emission tomography/computed tomography ( 68 Ga-DOTA-IBA PET/CT), 99m Tc-labelled methylene diphosphonate( 99m Tc-MDP) bone scintigraphy, and multidetector computed tomography (CT) in detecting bone metastases. Patients and Methods : This ongoing prospective trial, conducted between March 2022 and April 2024, enrolled 138 oncology patients (70 men and 68 women, aged 27 to 92 years). These individuals had either been diagnosed with or were under suspicion of having bone metastases. Each participant underwent 68 Ga-DOTA-IBA PET/CT, 99m Tc-MDP bone scintigraphy, and CT scans within one week. The resulting images were subsequently analyzed on an individual basis by seasoned radiologists and nuclear medicine specialists. Result: A total of 1628 lesions were identified as malignant, with 1521 (93.4%) detected using 68 Ga-DOTA-IBA PET/CT, with 1245 lesions (76.5%) identified through 99m Tc-MDP bone scintigraphy, and with 1350 lesions (82.9%) revealed by CT scanning. On an individual patient basis, the detection rate of bone metastases was 98.6% (136/138) for 68 Ga-DOTA-IBA PET/CT, 97.8% (135/138) for 99m Tc-MDP bone scintigraphy, and 95.7% (132/138) for CT. The maximum standardized uptake value (SUVmax) for malignant lesions was markedly higher than that observed in benign lesions (p<0.001). The area under the curve (AUC) for SUVmax, when diagnosing bone metastases with 68 Ga-DOTA-IBA PET/CT, was 0.969, utilizing a threshold of 4.6 to differentiate between benign and malignant lesions. Conclusion: 68 Ga-DOTA-IBA PET/CT has a higher detection rate for skeletal metastases than conventional bone scintigraphy or CT. The detection of occult bone metastases with 68 Ga-DOTA-IBA PET/CT is crucial for precise tumor staging and the formulation of therapeutic strategies. Bone metastases 68Ga-DOTA-IBA 99mTc-MDP bone scintigraphy computed tomography Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Bone is the most frequent site for distant metastasis of malignant tumors, following the lung and liver. Prostate, breast, lung, liver, and thyroid carcinomas are particularly prone to metastasizing to bone [ 1 – 3 ]. Complications associated with bone metastases encompass bone pain, pathological fractures (with an incidence ranging from 16–60%), hypercalcemia, and spinal cord compression, all of which significantly diminish patients' quality of life [ 4 – 6 ]. Early diagnosis and treatment of bone metastases are crucial for enhancing the quality of life and extending patient survival [ 7 – 8 ]. Routine skeletal scintigraphy (SS), utilizing technetium-99m-labeled bisphosphonates, although it is frequently recommended for the detection of bone metastases, its sensitivity and specificity have been reported to be less than optimal [ 9 – 11 ]. This is due to the fact that skeletal scintigraphic imaging depends on osteoblastic activity. Early bone metastases may be overlooked as metastatic cancer cells tend to be preferentially localized within the bone marrow microenvironment [ 12 ]. In addition to tumor formation, local trauma, infection, and degeneration can result in an increased accumulation of skeletal radionuclides. False-negative results can occur in the absence of reactive changes or in cases of slow-growing lesions, rapidly growing purely osteolytic metastases, or when there is a lack of vascularity at the site of growth (photon-deficient lesions, also known as 'cold spots') [ 13 – 14 ]. Although computed tomography (CT) is a routine method for detecting bone metastases, it often has limitations [ 15 – 16 ]. To enhance the diagnostic sensitivity and specificity of bone metastases, positron-emission tomography (PET) emerges as one of the most promising advanced imaging modalities. Ibandronic acid (IBA), a third-generation bisphosphonate, possesses anti-resorptive and anti-hypercalcemic properties. The successful synthesis of DOTA-IBA, a DOTA-conjugated ligand, offers a novel strategy for the diagnosis and treatment of bone metastases. In preclinical studies, 68 Ga/ 177 Lu-DOTA-IBA exhibits a high affinity for hydroxyapatite and a favorable target-to-background ratio and demonstrates rapid renal clearance, which are key characteristics for effective theranostic agents in bone metastases [ 17 ]. 68 Ga-labeled DOTA-ibandronic acid positron emission tomography/computed tomography ( 68 Ga-DOTA-IBA PET/CT), when compared to SS, demonstrated a higher detection rate of bone metastases across various solid tumors and may represent a useful imaging technique for bone metastases while offering a visual basis for 177 Lu-DOTA-IBA diagnosis and therapy response assessments for skeletal metastases [ 18 ]. Nevertheless, the scope of tumor types and cases included in existing studies assessing the diagnostic efficacy of 68 Ga-DOTA-IBA PET/CT is limited. Consequently, the objective of this study was to assess the diagnostic efficacy of 68 Ga-DOTA-IBA PET/CT, bone scintigraphy, and CT scanning for bone metastatic lesions across a range of tumors. Patients and Methods Patients This prospective study obtained approval from the Ethics Committee of the Affiliated Hospital of Southwest Medical University (Ethics Committee Approval Number: KY2022114; Clinical Trial Registration Number: ChiCTR2200064487). A total of 138 participants who consented to participate in this research were enrolled in a prospective manner between March 2022 and April 2024. Patients were categorized into those with confirmed bone metastases, as diagnosed through 99m Tc-MDP bone scintigraphy or CT scans, or those with suspected bone metastases, presenting with bone pain, bone mass, or neurological symptoms attributed to bone metastases. Imaging Weighing is the sole requirement prior to the 68 Ga-DOTA-IBA scan, with no additional preparatory steps required. The labeling of 68 Ga-DOTA-IBA is conducted as detailed in the preceding methodology, with an intravenous dose of 68 Ga-DOTA-IBA being 1.85 MBq/kg (corresponding to 0.05 mCi/kg) [ 17 ]. PET/CT imaging (uMI780, United Imaging Healthcare) was conducted approximately 45 to 60 minutes after the intravenous administration of the tracer. The CT scan parameters were as follows: tube voltage of 120 kV, current of 120 mA, slice thickness of 3.00 mm, slice interval of 5 mm, pitch of 0.813, and reconstructed with bone-specific algorithms. Subsequent PET scans were conducted using 3D acquisition mode, utilizing the same scanner bed as the CT. The resulting images underwent attenuation correction and iterative reconstruction, resulting in transverse, coronal, and sagittal views of the PET/CT scans. Bone scintigraphy was performed 3 to 4 hours after intravenous administration of 740–925 MBq (20–25 mCi) of 99m Tc-MDP. Whole-body planar bone scintigrams, both anterior and posterior, were obtained from the skull vertex to the toes. Additional imaging assessments should be conducted in compliance with established clinical guidelines in instances of overlapping structures within the pelvic region as observed on planar imaging, focal uptake of the radiotracer indicating areas of increased radiodensity, or in cases where it is infeasible to discern the benign or malignant nature of a lesion. SPECT imaging of pelvic and other localized regions was acquired in 25 minutes with a 128 × 128 matrix and a 50 × 40 cm field of view. Image Analysis The scans of 68 Ga-DOTA-IBA and 99m Tc-MDP bone scintigraphy were visually interpreted rather than semi-quantitatively assessed (i.e., using standardized uptake value [SUV] thresholds) in a random sequence by two experienced nuclear medicine physicians, who were unaware of the results from other diagnostic and imaging studies. T wo experienced radiologists interpreted CT scan images without knowledge of the outcomes from other diagnostic and imaging studies and in a random sequence. Discrepancies were resolved through direct comparison for each lesion identified across the three scans and through consensus interpretation. In the context of 68 Ga-DOTA-IBA and 99m Tc-MDP bone scintigraphy scans, focal areas of increased radiotracer uptake in 68 Ga-DOTA-IBA and 99m Tc-MDP bone scintigraphy were recorded as positive findings unless a benign cause for the uptake was confirmed at the corresponding site on the CT image (for example, degenerative changes, hemangioma). Lesions detected on CT scans were characterized as being either lytic (associated with low attenuation) or sclerotic (associated with high attenuation). The data collection process included the number of bone metastases per subject. SUVmax values of bone metastases, which show typical bone density changes and SUVmax values of specific benign lesions, such as osteophytes, bone cysts, bone islands, and hemangiomas, detected on 68 Ga-DOTA-IBA PET/CT scans, were also included. The reference standard for definitively detecting bone metastases encompasses the following criteria: (1) histopathological confirmation; (2) high-resolution imaging findings (MRI, CT, PET-CT, or a combination) independently assessed by two physicians; (3) progression of specific bone findings at follow-up, 2 months to 1 year from the baseline examination; (4) multifocal bone scintigraphy, 68 Ga-DOTA-IBA PET/CT, and CT scans demonstrating multifocal bone lesions with a typical appearance or an increasing number over time; and (5) posttreatment radiographic or CT imaging demonstrating osteosclerotic changes in bone lesions. Subsequently, two nuclear medicine physicians and two radiologists arrived at a consensus on the presence of bone metastases in each patient based on the available information. If the status of bone metastatic lesions could not be determined based on the available data, such cases were subsequently excluded from the analysis [ 19 ]. Statistics Statistical analyses were conducted utilizing SPSS version 27.0 (IBM Corporation, Armonk, New York, USA). This analysis aimed to compare the detection rate differences among the three tests using the McNemar test. Comparisons of SUVmax between lesions identified on 68 Ga-DOTA-IBA scans were performed using the Wilcoxon test, and the differentiation between benign and malignant lesions based on cut-off values was assessed using the receiver operating characteristic (ROC) curve. P-values less than 0.05 were considered statistically significant. Results Patient characteristics The clinical characteristics of the enrolled patients are shown in Table 1 . A total of 138 patients were enrolled in the trial and underwent 68 Ga-DOTA-IBA PET/CT, 99m Tc-MDP bone scintigraphy, and CT scans, all of which were completed within a week. Follow-up imaging was assessed for a period of up to 1 year post-study imaging, with a minimum interval of 2 months, attributable to patient death or discontinuation of further treatment. Table 1 Clinical Characteristics of Patient Population(N = 138) Characteristics Number Age 59.6 ± 12.7 Gender Female 69(49.6%) Male 70(50.4%) Primary tumor Lung cancer 44(31.9%) Prostate cancer 29(21.0%) Breast cancer 40(29.0%) Nasopharyngeal carcinoma 4(2.9%) Liver cancer 9(6.5%) Colorectal cancer 9(6.5%) Cervical cancer 2(1.4%) Multiple myeloma 1(0.7%) Indications for bone scintigraphy Initial treatment strategy 36(26.1%) Subsequent treatment strategy 102(73.9%) Comparative analysis in Ga-DOTA-IBA, Tc-MDP scintigraphy, and multidetector CT Following a thorough analysis of the three imaging modalities and follow-up results, a total of 1628 bone metastatic lesions were identified across all patients. Among them, 1521/1628(93.4%) were identified using 68 Ga-DOTA-IBA PET/CT, and 1245/1628(76.5%) using 99m Tc-MDP bone scintigraphy with SPECT. A total of 1350/1628(82.9%) bone metastases were identified through CT scans; 415 of these lesions exhibited osteolytic characteristics, while the remaining 935 demonstrated osteoblastic changes. The detection rates of the three imaging tests in the tumor subgroups are detailed in Table 2 . In conclusion, 68 Ga-DOTA-IBA PET/CT demonstrated a statistically significantly higher lesion detection rate compared to 99m Tc-MDP SPECT (P < 0.001) and CT imaging (P < 0.001). Table 2 The detection rate of 68 Ga-DOTA-IBA PET/CT、 99m Tc-MDP scintigraphy, and CT in metastatic lesions Types of cancer 68 Ga-DOTA-IBA PET/CT (%) 99m Tc-MDP scintigraphy (%) CT (%) P1 value P2 value Total lesions 1521/1628(93.4%) 1245/1628(76.5%) 1350/1628(82.9%) <0.001 <0.001 Lung cancer 338/355(95.2%) 265/355(74.6%) 304/355(85.6%) <0.001 <0.001 Prostate cancer 506/534(94.8%) 414/534(77.5%) 453/534(84.8%) <0.001 <0.001 Breast cancer 389/439(88.6%) 329/439(74.9%) 376/439(85.6%) <0.001 NS Liver cancer 121/124(97.6%) 110/124(88.7%) 96/124(77.4%) 0.003 <0.001 Colorectal cancer 87/91(95.6%) 75/91(82.4%) 68/91(74.7%) 0.002 <0.001 Abbreviations: P1 value: P value between 68 Ga-DOTA-IBA and 99m Tc-MDP scintigraphy, P2 value: the P value between 68 Ga-DOTA-IBA and CT, NS: not statistically significant. On an individual patient basis, the detection rate of bone metastases was 98.6% (136/138) for 68 Ga-DOTA-IBA PET/CT, 97.8% (135/138) for 99m Tc-MDP WBBS, and 95.7% (132/138) for CT. The detection rates of the three imaging tests in the tumor subgroups are detailed in Table 3 . No statistically significant differences were detected between 68 Ga-DOTA-IBA PET/CT and either 99m TcMDP WBBS or CT. Table 3 The detection rate of 68 Ga-DOTA-IBA PET/CT、 99m Tc-MDP scintigraphy, and CT in individual patients Types of cancer 68 Ga-DOTA-IBA PET/CT (%) 99m Tc-MDP scintigraphy (%) CT (%) Total lesions 136/138(98.6%) 135/138(97.8%) 132/138(95.7%) Lung cancer 44/44(100%) 43/44(97.73%) 41/44(93.2%) Prostate cancer 29/29(100%) 29/29(100%) 29/29(100%) Breast cancer 39/40(97.5%) 40/40(100%) 39/40(97.5%) Colorectal cancer 8/9(88.9%) 8/9(88.9%) 8/9(88.9%) Liver cancer 9/9(100%) 8/9(88.9%) 9/9(100%) Comparative analysis of SUVmax in Ga-DOTA-IBA PET/CT On ⁶⁸Ga-DOTA-IBA PET/CT scans using the maximum standardized uptake value (SUVmax), 642 malignant lesions and 599 benign lesions were identified. The SUVmax values of malignant lesions were significantly higher than those of benign lesions (p < 0.001): the median SUVmax of malignant lesions was 9.0 (range: 5.7–13.0), while the median SUVmax of benign lesions was 2.5 (range: 2.0-3.3). To assess the diagnostic performance, an ROC curve analysis was conducted based on SUVmax values from 68 Ga-DOTA-IBA PET/CT scans for benign and malignant lesions (as shown in Fig. 1 ). The findings revealed that the SUVmax AUC for diagnosing bone metastases in the total cancer on 68 Ga-DOTA-IBA PET/CT was 0.958, indicating that SUVmax values from 68 Ga-DOTA-IBA PET/CT demonstrated high accuracy in distinguishing between benign and malignant lesions. The maximum Yoden index calculated was 0.802, with the corresponding SUVmax threshold of 4.6. Furthermore, to determine if there were differences in SUVmax between osteolytic and osteogenic lesions, analyses were conducted using the Mann-Whitney U test, and the results indicated that the SUVmax of osteogenic lesions was significantly higher than that of osteolytic lesions (p < 0.001): the median SUVmax of osteogenic lesions was 10 (range 6.5–15.6), whereas the median SUVmax of osteolytic lesions was 7.4 (range 5.5-11.28). The ROC curve analysis of SUVmax for osteogenic and osteolytic lesions yielded an AUC of 0.635. This indicates that the use of SUVmax as a biomarker for distinguishing between these two types of lesions may not be sufficiently reliable for clinical decision-making. Discussion Previous studies compared the diagnostic efficacy of 68 Ga-DOTA-IBA PET/CT and bone scintigraphy for bone metastatic lesions, finding that the detection rate of 68 Ga-DOTA-IBA PET/CT was superior to that of bone scintigraphy for the lesions [ 17 – 18 , 20 ]. Our study was the first prospective study comparing the diagnostic efficacy of 68 Ga-DOTA-IBA PET/CT, 99m Tc-MDP bone scintigraphy, and CT scan for the diagnosis of bone metastases in nine malignant diseases, including lung, prostate, breast, and colorectal cancers, and a total of 138 participants were included. 68 Ga-DOTA-IBA PET/CT has the ability to identify occult bone metastases that are not discernible through conventional imaging techniques. The accurate detection of osseous metastases significantly impacts staging, treatment planning, and the monitoring of therapeutic responses[ 21 – 23 ]. It has been demonstrated that 68 Ga-DOTA-IBA PET/CT exhibits a higher detection rate for bone metastases compared to 99m Tc-MDP bone scintigraphy [ 17 , 20 ]. Xiang et al.[ 18 ] encompassed 45 patients with breast cancer and identified 546 bone metastatic lesions. The detection rate was significantly higher with 68 Ga-DOTA-IBA PET/CT at 100% (546/546) compared to 99m Tc-MDP WBBS at 67.8% (370/546). In a study conducted by Deng J et al. [ 24 ], 24 patients were enrolled to compare the diagnostic performance of 68 Ga-DOTA-IBA PET/CT and 18 F-NaF PET/CT for bone metastatic lesions. 68 Ga-DOTA-IBA PET/CT exhibited an 81% detection rate, and no significant difference was observed in the diagnostic performance when compared with 18 F-NaF PET/CT. The detection rate of 68 Ga-DOTA-IBA PET/CT in our study modestly varied from the results obtained in the aforementioned studies, potentially attributable to the number of cases included and the type of tumors encompassed. Additionally, CT imaging was incorporated into the present study. Although osteolytic bone destruction was identified on CT imaging, contrast uptake was not demonstrated on ⁶⁸GaDOTAIBA PET/CT or SPECT, thereby lowering the detection rate. Lesions that were identified as positive on 68 Ga-DOTA-IBA PET/CT images but negative on CT images were later confirmed to be bone metastases through subsequent follow-ups (as shown in Fig. 2 , Fig. 3 ). These findings may indicate early reactive changes of osteoblasts in response to metastatic deposits, highlighting the potential of 68 Ga-DOTA-IBA PET/CT to detect bone metastases at an earlier stage compared to CT imaging. Although the addition of SPECT to planar acquisitions enhances the diagnostic accuracy of BS in detecting malignant bone involvement [ 9 , 25 ], our findings indicate that 68 Ga-DOTA-IBA PET/CT possesses a superior detection rate. In comparison to conventional bone scintigraphy, 68 Ga-DOTA-IBA PET/CT exhibits superior spatial resolution. Given that obtaining tomographic images of the entire skeleton is standard clinical practice, unlike the need for additional localized tomographic acquisitions in 99m Tc-MDP SPECT, 68 Ga-DOTA-IBA PET/CT has a potential advantage in terms of sensitivity in detecting bone metastases. Furthermore, Ibandronate, a third-generation amino bisphosphonate, demonstrates a higher bone affinity compared to MDP and EDTMP. 68 Ga-DOTA-IBA PET/CT, utilizing the 68 Ga-labeled ligand DOTA-ibandronate, demonstrated a strong affinity for hydroxyapatite and favorable target-to-background ratios (as shown in Fig. 4 ). This is consistent with the findings from various studies that highlight the high bone targeting and target-to-non-target ratio for bone metastases with 68 Ga-DOTA-IBA [ 20 , 26 ]. This enhanced bone targeting capability is a key factor in the superior diagnostic performance of 68 Ga-DOTA-IBA PET/CT, as it allows for more precise localization of bone metastases [ 27 ]. 99m Tc-MDP bone scintigraphy, a commonly employed method for evaluating bone metastases in oncology patients, suffers from low specificity, resulting in a higher incidence of inconclusive findings [ 28 ]. Numerous pathological conditions, such as trauma, postoperative alterations, degenerative disorders, and infections, may result in false-positive scans, thereby complicating the differentiation between benign and malignant diseases[ 13 – 14 ]. Within the skull, distinguishing metastases from both normal anatomical variants, including arachnoid granulomas and venous lakes, and benign lesions presents a significant diagnostic challenge [ 29 ]. Our study employed a quantitative analysis of lesions detected by 68 Ga-DOTA-IBA PET/CT, establishing threshold values for contrast uptake that facilitate the differentiation of benign from malignant lesions, particularly in scenarios with diagnostic ambiguity. While our study demonstrated that 68 Ga-DOTA-IBA PET/CT possesses a high detection rate compared to both 99m Tc-MDP bone scintigraphy and CT, it remains the most costly and least accessible of the three imaging modalities under consideration. Such an analysis should consider improved patient outcomes associated with the early and accurate detection of bone metastases. This particular area remains unexplored in the context of our study. Future research should focus on conducting a comprehensive cost-effectiveness analysis to determine the practical implications and economic viability of implementing 68 Ga-DOTA-IBA PET/CT as a routine diagnostic tool for high-risk cancer patients. A second limitation of our study was the absence of a definitive diagnostic criterion, or gold standard, for confirming true bone metastasis. This limitation stemmed from the high prevalence of bone metastatic lesions among the patient cohort and the intricacies associated with PET-guided biopsies, which rendered pathological biopsy confirmation impractical, as highlighted in studies discussing the challenges and outcomes of PET/CT-guided interventions [ 30 ]. In our research, we elected to exclude lesions for which a definitive diagnosis of benignancy or malignancy could not be established through follow-up. This decision was critical to ensure that our analysis was based on a cohort with confirmed diagnoses, aligning with the rigorous standards of diagnostic accuracy in oncological imaging. Conclusion Our prospective study demonstrated that 68 Ga-DOTA-IBA PET/CT exhibits a higher detection rate compared to conventional 99m Tc-MDP bone scintigraphy and CT for the detection of bone metastases. In addition, high accuracy in differentiating between benign and malignant lesions is demonstrated by ⁶⁸GaDOTAIBA PET/CT. Declarations Acknowledgements We are grateful to the members of the Department of Nuclear Medicine, The Affiliated Hospital, Southwest Medical University, and Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province for their technical guidance, cooperation, and assistance in completing this study. We are also grateful for the financial support given by the major science and technology project in Gansu Province (23ZDFA014) and the school-level scientific research project of Southwest Medical University (Grant No. 2024ZKY082). Author Contributions Xinyi Lin, Na Zhang, Tingting Xu, and Yue Chen contributed to the study design, and Xinyi Lin wrote the manuscript. Xinyi Lin, Na Zhang, Rongliang Wang, Huajun Liu, and Wei Wang collected the clinical data of patients. Xinyi Lin and Na Zhang analyzed the clinical data of patients. Xinyi Lin and Na Zhang contributed equally to this paper and shared joint first authorship. Yue Chen and Tingting Xu were responsible for revising important intellectual content. Yue Chen and Tingting Xu contributed equally to this paper and shared joint corresponding authorship. All authors read and approved the final manuscript. All authors read and approved the final manuscript. Funding This work was supported by the major science and technology project in Gansu Province (23ZDFA014) and the school-level scientific research project of Southwest Medical University (Grant No. 2024ZKY082). Ethical Approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed Consent Informed consent was obtained from all individual participants included in the study. Conflict of Interest The authors declare that they have no conflict of interest. References Chow E, Loblaw A, Harris K et al (2007) Dexamethasone for the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases—a pilot study. Support Care Cancer 15:643–647 Gdowski AS, Ranjan A, Vishwanatha JK (2017) Current concepts in bone metastasis, contemporary therapeutic strategies and ongoing clinical trials. J Exp Clin Cancer Res 36(1):108 Siegel RL, Giaquinto AN, Jemal A (2024) Cancer statistics, 2024. 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Eur J Radiol 55:41–55 Yang J, Deng J, Fan D et al (2023) Biodistribution and Internal Dosimetry of 68 Ga-DOTA-IBA PET Imaging for Patients With Bone Metastases. Clin Nucl Med 48:847–852 Wang Q, Yang J, Wang Y et al (2023) Lutetium177-Labeled DOTA-Ibandronate: A Novel Radiopharmaceutical for Targeted Treatment of Bone Metastases. Mol Pharm 20:1788–1795 Nicolini A, Ferrari P, Sagripanti A, Carpi A (1999) The role of tumour markers in predicting skeletal metastases in breast cancer patients with equivocal bone scintigraphy. Br J Cancer 79:1443–1447 Gerety EL, Lawrence EM, Wason J et al (2015) Prospective study evaluating the relative sensitivity of 18 F-NaF PET/CT for detecting skeletal metastases from renal cell carcinoma in comparison to multidetector CT and 99m Tc-MDP bone scintigraphy, using an adaptive trial design. Ann Oncol 26:2113–2118 Wu MH, Xiao LF, Liu HW et al (2019) PET/CT-guided versus CT-guided percutaneous core biopsies in the diagnosis of bone tumors and tumor-like lesions: which is the better choice? Cancer Imaging 19:69 Supplementary Files 1540880coidisclosure.pdf 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-6656119","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":456843963,"identity":"7908a004-92dc-487a-a8a2-92fb365149cc","order_by":0,"name":"Xinyi Lin","email":"","orcid":"","institution":"The Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xinyi","middleName":"","lastName":"Lin","suffix":""},{"id":456843964,"identity":"9d5a9916-1cc3-459e-a29f-713804a21843","order_by":1,"name":"Na Zhang","email":"","orcid":"","institution":"The Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Na","middleName":"","lastName":"Zhang","suffix":""},{"id":456843965,"identity":"c1da2962-6183-4bba-ade7-d6e8b1d5d4b0","order_by":2,"name":"Rongliang Wang","email":"","orcid":"","institution":"The Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Rongliang","middleName":"","lastName":"Wang","suffix":""},{"id":456843966,"identity":"bf0136ce-404e-4126-9e88-ab6b1e4898f7","order_by":3,"name":"Huajun Liu","email":"","orcid":"","institution":"The Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Huajun","middleName":"","lastName":"Liu","suffix":""},{"id":456843967,"identity":"9d6cfe02-d651-4a3c-96de-fdeb91ad2e90","order_by":4,"name":"Wei Wang","email":"","orcid":"","institution":"The Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Wang","suffix":""},{"id":456843968,"identity":"8327859f-9b60-4c5c-930d-8db176d22bd0","order_by":5,"name":"Tingting Xu","email":"","orcid":"","institution":"The Affiliated Hospital of Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Tingting","middleName":"","lastName":"Xu","suffix":""},{"id":456843969,"identity":"c96526c3-0644-428d-b4d3-937ea3f3075e","order_by":6,"name":"Yue Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIiWNgGAWjYDACCQhVb9/efvBBQoUN8VoSDHjOJBs8OJNGihaJBDPJh22HCOvgn9187DFvm02eOUNCWkUC2wEG/vbuBPyW3DmWbszbllZs2XDw2I0EnjsMEmfObsCrxUAix0yat+0wY8PBhrQbCRLPgCK5hLTkfwNq+c/YcJjBrCDB4DAxWnLYgFoOJG44xmDGkJBAhBaJG2lmknPOJRtL9vAkSyQcSOMh6Bf+GcnPJN6U2cnxyz8/+PHnPxs5/vZe/FpAgIkHicODUxkyYPxBlLJRMApGwSgYsQAA6xhKxjr2kSsAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0003-4088-7649","institution":"The affiliated hospital,Southwest Medical University","correspondingAuthor":true,"prefix":"","firstName":"Yue","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-05-13 13:52:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6656119/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6656119/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83158407,"identity":"efeefd26-a4f3-403b-a6a4-11d5727c264e","added_by":"auto","created_at":"2025-05-20 14:54:56","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":586823,"visible":true,"origin":"","legend":"\u003cp\u003eROC curves comparing the SUVmax of bone metastatic lesions to benign lesions in \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6656119/v1/8ac0ce9878eba83974cfef74.jpg"},{"id":83158406,"identity":"8f542ddc-a93c-4f18-8bc3-478140778b0d","added_by":"auto","created_at":"2025-05-20 14:54:56","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":509226,"visible":true,"origin":"","legend":"\u003cp\u003eA 77-year-old woman with metastatic breast cancer. (\u003cstrong\u003eA, E) \u003c/strong\u003eMIP and axial images demonstrate elevated \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA uptake in multiple lesions throughout the body. On the selected transaxial images of the chest (\u003cstrong\u003eB\u003c/strong\u003e, PET; \u003cstrong\u003eC\u003c/strong\u003e, CT; \u003cstrong\u003eD\u003c/strong\u003e, fusion image), \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA exhibited positive contrast uptake in the right rib on PET/CT, with no significant changes observed in the bone on CT (\u003cstrong\u003eC\u003c/strong\u003e, curved arrow). After 2 months, the selected transaxial images of the chest (\u003cstrong\u003eF\u003c/strong\u003e, PET; \u003cstrong\u003eG\u003c/strong\u003e, CT; \u003cstrong\u003eH\u003c/strong\u003e, fusion image) revealed osteogenic bone destruction on CT (\u003cstrong\u003eG\u003c/strong\u003e, curved arrow).\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6656119/v1/53f48aa4e95a6d81dcd2bdac.jpg"},{"id":83159532,"identity":"5e3398f2-de41-453f-b04d-5baee1614c85","added_by":"auto","created_at":"2025-05-20 15:02:56","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":517385,"visible":true,"origin":"","legend":"\u003cp\u003eA 48-year-old woman with metastatic breast cancer. (\u003cstrong\u003eA, E\u003c/strong\u003e) MIP and axial images demonstrate elevated \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA uptake in multiple lesions throughout the body. On the selected transaxial images of the skull (\u003cstrong\u003eB\u003c/strong\u003e, PET; \u003cstrong\u003eC\u003c/strong\u003e, CT; \u003cstrong\u003eD\u003c/strong\u003e, fusion image), \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA exhibited positive contrast uptake in he left zygomatic bone on PET/CT, with no significant changes observed in the bone on CT (\u003cstrong\u003eC\u003c/strong\u003e, straight arrow). After 3 months, the selected transaxial images of the skull (\u003cstrong\u003eF\u003c/strong\u003e, PET; \u003cstrong\u003eG\u003c/strong\u003e, CT; \u003cstrong\u003eH\u003c/strong\u003e, fusion image) revealed osteogenic bone destruction on CT (\u003cstrong\u003eG\u003c/strong\u003e, straight arrow).\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6656119/v1/ba5bdea2086d5ea503b1f514.jpg"},{"id":83158408,"identity":"9f43c3bf-709b-4812-85df-70023ea9e7f2","added_by":"auto","created_at":"2025-05-20 14:54:56","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":108500,"visible":true,"origin":"","legend":"\u003cp\u003eA direct comparison of \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scintigraphy and \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT images in a prostate cancer patient was conducted over a one-week interval. An 80-year-old man with metastatic prostate cancer. \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT(\u003cstrong\u003eB\u003c/strong\u003e) demonstrated a higher number of bone metastatic lesions when compared with a \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scan(\u003cstrong\u003eA\u003c/strong\u003e) and presented them with greater clarity.\u003c/p\u003e","description":"","filename":"FIGURE4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6656119/v1/3ac9d7166ee1fc09789fccc9.jpg"},{"id":84237480,"identity":"b480d7be-d9c9-443b-bdc0-4bf485ea8307","added_by":"auto","created_at":"2025-06-09 15:15:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2459982,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6656119/v1/b88e15e8-0a39-46da-b5ea-94bf6cd1c62a.pdf"},{"id":83159535,"identity":"09266c65-941e-467a-bac6-5c0a7e123782","added_by":"auto","created_at":"2025-05-20 15:02:57","extension":"pdf","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":1247303,"visible":true,"origin":"","legend":"","description":"","filename":"1540880coidisclosure.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6656119/v1/4717496e6c6965b0b44fc7bd.pdf"}],"financialInterests":"","formattedTitle":"Prospective Comparison of 68Ga-DOTA-IBA, 99mTc-MDP Scintigraphy, and Multidetector CT for Skeletal Metastases","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBone is the most frequent site for distant metastasis of malignant tumors, following the lung and liver. Prostate, breast, lung, liver, and thyroid carcinomas are particularly prone to metastasizing to bone [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Complications associated with bone metastases encompass bone pain, pathological fractures (with an incidence ranging from 16\u0026ndash;60%), hypercalcemia, and spinal cord compression, all of which significantly diminish patients' quality of life [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Early diagnosis and treatment of bone metastases are crucial for enhancing the quality of life and extending patient survival [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRoutine skeletal scintigraphy (SS), utilizing technetium-99m-labeled bisphosphonates, although it is frequently recommended for the detection of bone metastases, its sensitivity and specificity have been reported to be less than optimal [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This is due to the fact that skeletal scintigraphic imaging depends on osteoblastic activity. Early bone metastases may be overlooked as metastatic cancer cells tend to be preferentially localized within the bone marrow microenvironment [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In addition to tumor formation, local trauma, infection, and degeneration can result in an increased accumulation of skeletal radionuclides. False-negative results can occur in the absence of reactive changes or in cases of slow-growing lesions, rapidly growing purely osteolytic metastases, or when there is a lack of vascularity at the site of growth (photon-deficient lesions, also known as 'cold spots') [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Although computed tomography (CT) is a routine method for detecting bone metastases, it often has limitations [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. To enhance the diagnostic sensitivity and specificity of bone metastases, positron-emission tomography (PET) emerges as one of the most promising advanced imaging modalities.\u003c/p\u003e \u003cp\u003eIbandronic acid (IBA), a third-generation bisphosphonate, possesses anti-resorptive and anti-hypercalcemic properties. The successful synthesis of DOTA-IBA, a DOTA-conjugated ligand, offers a novel strategy for the diagnosis and treatment of bone metastases. In preclinical studies, \u003csup\u003e68\u003c/sup\u003eGa/\u003csup\u003e177\u003c/sup\u003eLu-DOTA-IBA exhibits a high affinity for hydroxyapatite and a favorable target-to-background ratio and demonstrates rapid renal clearance, which are key characteristics for effective theranostic agents in bone metastases [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. \u003csup\u003e68\u003c/sup\u003eGa-labeled DOTA-ibandronic acid positron emission tomography/computed tomography (\u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT), when compared to SS, demonstrated a higher detection rate of bone metastases across various solid tumors and may represent a useful imaging technique for bone metastases while offering a visual basis for \u003csup\u003e177\u003c/sup\u003eLu-DOTA-IBA diagnosis and therapy response assessments for skeletal metastases [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Nevertheless, the scope of tumor types and cases included in existing studies assessing the diagnostic efficacy of \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT is limited. Consequently, the objective of this study was to assess the diagnostic efficacy of \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT, bone scintigraphy, and CT scanning for bone metastatic lesions across a range of tumors.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003e This prospective study obtained approval from the Ethics Committee of the Affiliated Hospital of Southwest Medical University (Ethics Committee Approval Number: KY2022114; Clinical Trial Registration Number: ChiCTR2200064487). A total of 138 participants who consented to participate in this research were enrolled in a prospective manner between March 2022 and April 2024. Patients were categorized into those with confirmed bone metastases, as diagnosed through \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scintigraphy or CT scans, or those with suspected bone metastases, presenting with bone pain, bone mass, or neurological symptoms attributed to bone metastases.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eImaging\u003c/h3\u003e\n\u003cp\u003eWeighing is the sole requirement prior to the \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA scan, with no additional preparatory steps required. The labeling of \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA is conducted as detailed in the preceding methodology, with an intravenous dose of \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA being 1.85 MBq/kg (corresponding to 0.05 mCi/kg) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. PET/CT imaging (uMI780, United Imaging Healthcare) was conducted approximately 45 to 60 minutes after the intravenous administration of the tracer. The CT scan parameters were as follows: tube voltage of 120 kV, current of 120 mA, slice thickness of 3.00 mm, slice interval of 5 mm, pitch of 0.813, and reconstructed with bone-specific algorithms. Subsequent PET scans were conducted using 3D acquisition mode, utilizing the same scanner bed as the CT. The resulting images underwent attenuation correction and iterative reconstruction, resulting in transverse, coronal, and sagittal views of the PET/CT scans.\u003c/p\u003e \u003cp\u003eBone scintigraphy was performed 3 to 4 hours after intravenous administration of 740\u0026ndash;925 MBq (20\u0026ndash;25 mCi) of \u003csup\u003e99m\u003c/sup\u003eTc-MDP. Whole-body planar bone scintigrams, both anterior and posterior, were obtained from the skull vertex to the toes. Additional imaging assessments should be conducted in compliance with established clinical guidelines in instances of overlapping structures within the pelvic region as observed on planar imaging, focal uptake of the radiotracer indicating areas of increased radiodensity, or in cases where it is infeasible to discern the benign or malignant nature of a lesion. SPECT imaging of pelvic and other localized regions was acquired in 25 minutes with a 128 \u0026times; 128 matrix and a 50 \u0026times; 40 cm field of view.\u003c/p\u003e\n\u003ch3\u003eImage Analysis\u003c/h3\u003e\n\u003cp\u003eThe scans of \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA and \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scintigraphy were visually interpreted rather than semi-quantitatively assessed (i.e., using standardized uptake value [SUV] thresholds) in a random sequence by two experienced nuclear medicine physicians, who were unaware of the results from other diagnostic and imaging studies. \u003cb\u003eT\u003c/b\u003ewo experienced radiologists interpreted CT scan images without knowledge of the outcomes from other diagnostic and imaging studies and in a random sequence. Discrepancies were resolved through direct comparison for each lesion identified across the three scans and through consensus interpretation. In the context of \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA and \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scintigraphy scans, focal areas of increased radiotracer uptake in \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA and \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scintigraphy were recorded as positive findings unless a benign cause for the uptake was confirmed at the corresponding site on the CT image (for example, degenerative changes, hemangioma). Lesions detected on CT scans were characterized as being either lytic (associated with low attenuation) or sclerotic (associated with high attenuation). The data collection process included the number of bone metastases per subject. SUVmax values of bone metastases, which show typical bone density changes and SUVmax values of specific benign lesions, such as osteophytes, bone cysts, bone islands, and hemangiomas, detected on \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT scans, were also included.\u003c/p\u003e \u003cp\u003eThe reference standard for definitively detecting bone metastases encompasses the following criteria: (1) histopathological confirmation; (2) high-resolution imaging findings (MRI, CT, PET-CT, or a combination) independently assessed by two physicians; (3) progression of specific bone findings at follow-up, 2 months to 1 year from the baseline examination; (4) multifocal bone scintigraphy, \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT, and CT scans demonstrating multifocal bone lesions with a typical appearance or an increasing number over time; and (5) posttreatment radiographic or CT imaging demonstrating osteosclerotic changes in bone lesions. Subsequently, two nuclear medicine physicians and two radiologists arrived at a consensus on the presence of bone metastases in each patient based on the available information. If the status of bone metastatic lesions could not be determined based on the available data, such cases were subsequently excluded from the analysis [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eStatistics\u003c/h3\u003e\n\u003cp\u003eStatistical analyses were conducted utilizing SPSS version 27.0 (IBM Corporation, Armonk, New York, USA). This analysis aimed to compare the detection rate differences among the three tests using the McNemar test. Comparisons of SUVmax between lesions identified on \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA scans were performed using the Wilcoxon test, and the differentiation between benign and malignant lesions based on cut-off values was assessed using the receiver operating characteristic (ROC) curve. P-values less than 0.05 were considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eThe clinical characteristics of the enrolled patients are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. A total of 138 patients were enrolled in the trial and underwent \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT, \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scintigraphy, and CT scans, all of which were completed within a week. Follow-up imaging was assessed for a period of up to 1 year post-study imaging, with a minimum interval of 2 months, attributable to patient death or discontinuation of further treatment.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical Characteristics of Patient Population(N\u0026thinsp;=\u0026thinsp;138)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.6\u0026thinsp;\u0026plusmn;\u0026thinsp;12.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69(49.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70(50.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrimary tumor\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44(31.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProstate cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29(21.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40(29.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNasopharyngeal carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(2.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(6.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColorectal cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(6.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCervical cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(1.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple myeloma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(0.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIndications for bone scintigraphy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInitial treatment strategy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36(26.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubsequent treatment strategy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e102(73.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eComparative analysis in Ga-DOTA-IBA, Tc-MDP scintigraphy, and multidetector CT\u003c/h3\u003e\n\u003cp\u003eFollowing a thorough analysis of the three imaging modalities and follow-up results, a total of 1628 bone metastatic lesions were identified across all patients. Among them, 1521/1628(93.4%) were identified using \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT, and 1245/1628(76.5%) using \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scintigraphy with SPECT. A total of 1350/1628(82.9%) bone metastases were identified through CT scans; 415 of these lesions exhibited osteolytic characteristics, while the remaining 935 demonstrated osteoblastic changes. The detection rates of the three imaging tests in the tumor subgroups are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. In conclusion, \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT demonstrated a statistically significantly higher lesion detection rate compared to \u003csup\u003e99m\u003c/sup\u003eTc-MDP SPECT (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and CT imaging (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe detection rate of \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT、\u003csup\u003e99m\u003c/sup\u003eTc-MDP scintigraphy, and CT in metastatic lesions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTypes of cancer\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003csup\u003e99m\u003c/sup\u003eTc-MDP scintigraphy (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCT (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP1 value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP2 value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1521/1628(93.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1245/1628(76.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1350/1628(82.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e338/355(95.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e265/355(74.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e304/355(85.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProstate cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e506/534(94.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e414/534(77.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e453/534(84.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e389/439(88.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e329/439(74.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e376/439(85.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e121/124(97.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e110/124(88.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e96/124(77.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColorectal cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e87/91(95.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e75/91(82.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e68/91(74.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: P1 value: P value between \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA and \u003csup\u003e99m\u003c/sup\u003eTc-MDP scintigraphy, P2 value: the P value between \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA and CT, NS: not statistically significant.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOn an individual patient basis, the detection rate of bone metastases was 98.6% (136/138) for \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT, 97.8% (135/138) for \u003csup\u003e99m\u003c/sup\u003eTc-MDP WBBS, and 95.7% (132/138) for CT. The detection rates of the three imaging tests in the tumor subgroups are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. No statistically significant differences were detected between \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT and either \u003csup\u003e99m\u003c/sup\u003eTcMDP WBBS or CT.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe detection rate of \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT、\u003csup\u003e99m\u003c/sup\u003eTc-MDP scintigraphy, and CT in individual patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTypes of cancer\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003csup\u003e99m\u003c/sup\u003eTc-MDP scintigraphy (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCT (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e136/138(98.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e135/138(97.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e132/138(95.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44/44(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43/44(97.73%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41/44(93.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProstate cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29/29(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29/29(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29/29(100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39/40(97.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40/40(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39/40(97.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColorectal cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8/9(88.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8/9(88.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8/9(88.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9/9(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8/9(88.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9/9(100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eComparative analysis of SUVmax in Ga-DOTA-IBA PET/CT\u003c/h3\u003e\n\u003cp\u003eOn ⁶⁸Ga-DOTA-IBA PET/CT scans using the maximum standardized uptake value (SUVmax), 642 malignant lesions and 599 benign lesions were identified. The SUVmax values of malignant lesions were significantly higher than those of benign lesions (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001): the median SUVmax of malignant lesions was 9.0 (range: 5.7\u0026ndash;13.0), while the median SUVmax of benign lesions was 2.5 (range: 2.0-3.3). To assess the diagnostic performance, an ROC curve analysis was conducted based on SUVmax values from \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT scans for benign and malignant lesions (as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The findings revealed that the SUVmax AUC for diagnosing bone metastases in the total cancer on \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT was 0.958, indicating that SUVmax values from \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT demonstrated high accuracy in distinguishing between benign and malignant lesions. The maximum Yoden index calculated was 0.802, with the corresponding SUVmax threshold of 4.6. Furthermore, to determine if there were differences in SUVmax between osteolytic and osteogenic lesions, analyses were conducted using the Mann-Whitney U test, and the results indicated that the SUVmax of osteogenic lesions was significantly higher than that of osteolytic lesions (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001): the median SUVmax of osteogenic lesions was 10 (range 6.5\u0026ndash;15.6), whereas the median SUVmax of osteolytic lesions was 7.4 (range 5.5-11.28). The ROC curve analysis of SUVmax for osteogenic and osteolytic lesions yielded an AUC of 0.635. This indicates that the use of SUVmax as a biomarker for distinguishing between these two types of lesions may not be sufficiently reliable for clinical decision-making.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePrevious studies compared the diagnostic efficacy of \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT and bone scintigraphy for bone metastatic lesions, finding that the detection rate of \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT was superior to that of bone scintigraphy for the lesions [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Our study was the first prospective study comparing the diagnostic efficacy of \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT, \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scintigraphy, and CT scan for the diagnosis of bone metastases in nine malignant diseases, including lung, prostate, breast, and colorectal cancers, and a total of 138 participants were included.\u003c/p\u003e \u003cp\u003e \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT has the ability to identify occult bone metastases that are not discernible through conventional imaging techniques. The accurate detection of osseous metastases significantly impacts staging, treatment planning, and the monitoring of therapeutic responses[\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. It has been demonstrated that \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT exhibits a higher detection rate for bone metastases compared to \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scintigraphy [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Xiang et al.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] encompassed 45 patients with breast cancer and identified 546 bone metastatic lesions. The detection rate was significantly higher with \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT at 100% (546/546) compared to \u003csup\u003e99m\u003c/sup\u003eTc-MDP WBBS at 67.8% (370/546). In a study conducted by Deng J et al. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], 24 patients were enrolled to compare the diagnostic performance of \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT and \u003csup\u003e18\u003c/sup\u003eF-NaF PET/CT for bone metastatic lesions. \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT exhibited an 81% detection rate, and no significant difference was observed in the diagnostic performance when compared with \u003csup\u003e18\u003c/sup\u003eF-NaF PET/CT. The detection rate of \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT in our study modestly varied from the results obtained in the aforementioned studies, potentially attributable to the number of cases included and the type of tumors encompassed. Additionally, CT imaging was incorporated into the present study. Although osteolytic bone destruction was identified on CT imaging, contrast uptake was not demonstrated on ⁶⁸GaDOTAIBA PET/CT or SPECT, thereby lowering the detection rate.\u003c/p\u003e \u003cp\u003eLesions that were identified as positive on \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT images but negative on CT images were later confirmed to be bone metastases through subsequent follow-ups (as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). These findings may indicate early reactive changes of osteoblasts in response to metastatic deposits, highlighting the potential of \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT to detect bone metastases at an earlier stage compared to CT imaging. Although the addition of SPECT to planar acquisitions enhances the diagnostic accuracy of BS in detecting malignant bone involvement [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], our findings indicate that \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT possesses a superior detection rate. In comparison to conventional bone scintigraphy, \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT exhibits superior spatial resolution. Given that obtaining tomographic images of the entire skeleton is standard clinical practice, unlike the need for additional localized tomographic acquisitions in \u003csup\u003e99m\u003c/sup\u003eTc-MDP SPECT, \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT has a potential advantage in terms of sensitivity in detecting bone metastases. Furthermore, Ibandronate, a third-generation amino bisphosphonate, demonstrates a higher bone affinity compared to MDP and EDTMP. \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT, utilizing the \u003csup\u003e68\u003c/sup\u003eGa-labeled ligand DOTA-ibandronate, demonstrated a strong affinity for hydroxyapatite and favorable target-to-background ratios (as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). This is consistent with the findings from various studies that highlight the high bone targeting and target-to-non-target ratio for bone metastases with \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. This enhanced bone targeting capability is a key factor in the superior diagnostic performance of \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT, as it allows for more precise localization of bone metastases [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scintigraphy, a commonly employed method for evaluating bone metastases in oncology patients, suffers from low specificity, resulting in a higher incidence of inconclusive findings [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Numerous pathological conditions, such as trauma, postoperative alterations, degenerative disorders, and infections, may result in false-positive scans, thereby complicating the differentiation between benign and malignant diseases[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Within the skull, distinguishing metastases from both normal anatomical variants, including arachnoid granulomas and venous lakes, and benign lesions presents a significant diagnostic challenge [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Our study employed a quantitative analysis of lesions detected by \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT, establishing threshold values for contrast uptake that facilitate the differentiation of benign from malignant lesions, particularly in scenarios with diagnostic ambiguity.\u003c/p\u003e \u003cp\u003eWhile our study demonstrated that \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT possesses a high detection rate compared to both \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scintigraphy and CT, it remains the most costly and least accessible of the three imaging modalities under consideration. Such an analysis should consider improved patient outcomes associated with the early and accurate detection of bone metastases. This particular area remains unexplored in the context of our study. Future research should focus on conducting a comprehensive cost-effectiveness analysis to determine the practical implications and economic viability of implementing \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT as a routine diagnostic tool for high-risk cancer patients. A second limitation of our study was the absence of a definitive diagnostic criterion, or gold standard, for confirming true bone metastasis. This limitation stemmed from the high prevalence of bone metastatic lesions among the patient cohort and the intricacies associated with PET-guided biopsies, which rendered pathological biopsy confirmation impractical, as highlighted in studies discussing the challenges and outcomes of PET/CT-guided interventions [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In our research, we elected to exclude lesions for which a definitive diagnosis of benignancy or malignancy could not be established through follow-up. This decision was critical to ensure that our analysis was based on a cohort with confirmed diagnoses, aligning with the rigorous standards of diagnostic accuracy in oncological imaging.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur prospective study demonstrated that \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT exhibits a higher detection rate compared to conventional \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scintigraphy and CT for the detection of bone metastases. In addition, high accuracy in differentiating between benign and malignant lesions is demonstrated by ⁶⁸GaDOTAIBA PET/CT.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003eWe are grateful to the members of the Department of Nuclear Medicine, The Affiliated Hospital, Southwest Medical University, and Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province for their technical guidance, cooperation, and assistance in completing this study. We are also grateful for the financial support given by the major science and technology project in Gansu Province (23ZDFA014) and the school-level scientific research project of Southwest Medical University (Grant No. 2024ZKY082).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e Xinyi Lin, Na Zhang, Tingting Xu, and Yue Chen contributed to the study design, and Xinyi Lin wrote the manuscript. Xinyi Lin, Na Zhang, Rongliang Wang, Huajun Liu, and Wei Wang collected the clinical data of patients. Xinyi Lin and Na Zhang analyzed the clinical data of patients. Xinyi Lin and Na Zhang contributed equally to this paper and shared joint first authorship. Yue Chen and Tingting Xu were responsible for revising important intellectual content. Yue Chen and Tingting Xu contributed equally to this paper and shared joint corresponding authorship. All authors read and approved the final manuscript. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e This work was supported by the major science and technology project in Gansu Province (23ZDFA014) and the school-level scientific research project of Southwest Medical University (Grant No. 2024ZKY082).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval\u0026nbsp;\u003c/strong\u003eAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent\u0026nbsp;\u003c/strong\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003ch4\u003eConflict of Interest The authors declare that they have no conflict of interest.\u003c/h4\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChow E, Loblaw A, Harris K et al (2007) Dexamethasone for the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases\u0026mdash;a pilot study. 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Clin Radiol 23:295\u0026ndash;297\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoriuchi-Suzuki K, Konno A, Ueda M et al (2004) Skeletal affinity of Tc(V)-DMS is bone cell mediated and pH dependent. Eur J Nucl Med Mol Imaging 31:388\u0026ndash;398\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNoguchi S, Nishio M, Sakamoto R et al (2022) Deep learning-based algorithm improved radiologists' performance in bone metastases detection on CT. Eur Radiol 32:7976\u0026ndash;7987\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuo H, Zou L, Yang Q et al (2024) Spectral CT assists differentiation of osteoblastic bone metastasis from bone island in newly diagnosed cancer patients. 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Front Oncol 14:1428498\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eB\u0026eacute;nard F, Harsini S, Wilson D et al (2022) Intra-individual comparison of \u003csup\u003e18\u003c/sup\u003eF-sodium fluoride PET\u0026ndash;CT and \u003csup\u003e99m\u003c/sup\u003eTc bone scintigraphy with SPECT in patients with prostate cancer or breast cancer at high risk for skeletal metastases (MITNEC-A1): a multicentre, phase 3 trial. Lancet Oncol 23:1499\u0026ndash;1507\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Y, Wang Q, Chen Z et al (2022) Preparation, biological characterization and preliminary human imaging studies of \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA. Front Oncol 12:1027792\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evon Moos R, Costa L, Gonzalez-Suarez E, Terpos E, Niepel D, Body JJ (2019) Management of bone health in solid tumours: From bisphosphonates to a monoclonal antibody. 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Mol Pharm 20:1788\u0026ndash;1795\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNicolini A, Ferrari P, Sagripanti A, Carpi A (1999) The role of tumour markers in predicting skeletal metastases in breast cancer patients with equivocal bone scintigraphy. Br J Cancer 79:1443\u0026ndash;1447\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGerety EL, Lawrence EM, Wason J et al (2015) Prospective study evaluating the relative sensitivity of \u003csup\u003e18\u003c/sup\u003eF-NaF PET/CT for detecting skeletal metastases from renal cell carcinoma in comparison to multidetector CT and \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scintigraphy, using an adaptive trial design. Ann Oncol 26:2113\u0026ndash;2118\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu MH, Xiao LF, Liu HW et al (2019) PET/CT-guided versus CT-guided percutaneous core biopsies in the diagnosis of bone tumors and tumor-like lesions: which is the better choice? Cancer Imaging 19:69\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":"Bone metastases, 68Ga-DOTA-IBA, 99mTc-MDP bone scintigraphy, computed tomography","lastPublishedDoi":"10.21203/rs.3.rs-6656119/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6656119/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: This prospective study was to evaluate the diagnostic efficacy of \u003csup\u003e68\u003c/sup\u003eGa-labeled DOTA-ibandronic acid positron emission tomography/computed tomography (\u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT), \u003csup\u003e99m\u003c/sup\u003eTc-labelled methylene diphosphonate(\u003csup\u003e99m\u003c/sup\u003eTc-MDP) bone scintigraphy, and multidetector computed tomography (CT) in detecting bone metastases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatients and Methods\u003c/strong\u003e: This ongoing prospective trial, conducted between March 2022 and April 2024, enrolled 138 oncology patients (70 men and 68 women, aged 27 to 92 years). These individuals had either been diagnosed with or were under suspicion of having bone metastases. Each participant underwent \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT, \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scintigraphy, and CT scans within one week. The resulting images were subsequently analyzed on an individual basis by seasoned radiologists and nuclear medicine specialists.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResult:\u003c/strong\u003e A total of 1628 lesions were identified as malignant, with 1521 (93.4%) detected using \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT, with 1245 lesions (76.5%) identified through \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scintigraphy, and with 1350 lesions (82.9%) revealed by CT scanning. On an individual patient basis, the detection rate of bone metastases was 98.6% (136/138) for \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT, 97.8% (135/138) for \u003csup\u003e99m\u003c/sup\u003eTc-MDP bone scintigraphy, and 95.7% (132/138) for CT. The maximum standardized uptake value (SUVmax) for malignant lesions was markedly higher than that observed in benign lesions (p\u0026lt;0.001). The area under the curve (AUC) for SUVmax, when diagnosing bone metastases with \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT, was 0.969, utilizing a threshold of 4.6 to differentiate between benign and malignant lesions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT has a higher detection rate for skeletal metastases than conventional bone scintigraphy or CT. The detection of occult bone metastases with \u003csup\u003e68\u003c/sup\u003eGa-DOTA-IBA PET/CT is crucial for precise tumor staging and the formulation of therapeutic strategies.\u003c/p\u003e","manuscriptTitle":"Prospective Comparison of 68Ga-DOTA-IBA, 99mTc-MDP Scintigraphy, and Multidetector CT for Skeletal Metastases","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-20 14:54:52","doi":"10.21203/rs.3.rs-6656119/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":"75ac5c27-b980-47aa-b4ba-2b102ed58fa2","owner":[],"postedDate":"May 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-09T15:06:58+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-20 14:54:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6656119","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6656119","identity":"rs-6656119","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}