Prognostic significance of 68Ga-FAPI-PET/CT in patients with bone metastases in various cancers

Prognostic significance of 68Ga-FAPI-PET/CT in patients with bone metastases in various cancers | 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 Prognostic significance of 68Ga-FAPI-PET/CT in patients with bone metastases in various cancers HACI ARAK, Umut Elboga, Yusuf Burak Cayırlı, Aydın Aytekin This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3973887/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Apr, 2024 Read the published version in Annals of Nuclear Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract Objective: This study aimed to compare and 18 FDGPET/CT in patients who develop bone metastases due to various cancers and to investigate the prognostic significance of the 68 FAPI-PET/CT SUVmax value for survival. Methods: Patients with bone metastases who underwent both 68 Ga-FAPI PET/CTand 18 FDGPET/CT within a 1-week period were included in this retrospective study. The effect of the SUVmax value of bone lesions on overall survival was analyzed. Results: A total of 75 eligible patients with 139 bone lesions were included in this study. The median age of the patients was 55(30–83) and 48 patients (64%) were newly diagnosed. The primary lesion median 68 Ga-FAPI PET/CT SUVmax value was higher than the median 18 FDGPET/CT SUVmax (10.75 versus 6.7). Bone lesions 68 Ga-FAPI PET/CT SUVmax median(IQR) were 7.8(4.6–13.2), and 18 FDGPET/CT SUVmax of bone lesions were 5.9(3.8–8.2). More bone lesions were detected on 68 Ga-FAPI PET/CT than on 18 FDGPET/CT(median IQR 4 [1–9] versus 2 [1–6](p=0.014). The extra lesions observed on 68 Ga-FAPI PET/CT were mostly sclerotic bone lesions(p = 0.001). 68 Ga-FAPI PET/CT SUVmax was significantly higher in vertebra and thorax lesions(p=0.011 and p=0.018, respectively). While the bone lesion 68 Ga-FAPI PET/CT SUVmax affected the OS, the 18 FDGPET/CT SUVmax value did not affect the OS (p7.7 was found for OS(AUC:0.619). The median OS in the group above the cut-off value was worse than that in the group below the cut-off value (32 versus 45) months (p=0.002). In the multivariate analysis for OS, the 68 Ga-FAPI PET/CT SUVmax of bone lesions was an important parameter,as well as cancer subtype, ALP level, and disease occurrence. Conclusions: 68 Ga-FAPI PET/CT detected more bone lesions and higher SUVmax values than 18 FDGPET/CT in various cancers. The prognostic value of the SUVmax value of 68 Ga-FAPI PET/CT bone lesions was observed regardless of disease subtype. 68Ga-FAPI PET/CT SUVmax prognosis bone metastasis Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Bone metastasis is common in certain advanced-stage cancers, particularly in prostate, breast, lung, thyroid, renal cell, gynecologic, and melanoma cancers. The occurrence of skeletal-related events, including pain, pathological fractures, hypercalcemia, and spinal cord compression, is a common consequence of bone metastases. Skeletal events negatively affect the quality of life of patients with cancer( 1 ). Therefore, early and accurate detection of bone metastases is crucial, both during the initial diagnosis and recurrence. Radiography, technetium-99m (Tc-99m) skeletal scintigraphy, computed tomography (CT), magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose-positron emission tomography ( 18 F-FDGPET) can be used to detect bone metastases. However, these methods have limitations. Radiography exhibits low sensitivity and specificity, while bone scintigraphy allows for limited detection of lytic lesions. 18 FDGPET/CT may yield inaccurate results in cases of infection, arthritis, and benign bone lesions. CT and MRI are unsuitable for whole-body bone scans,and there are technical challenges in MRI, along with nephrotoxic side effects of contrast solutionsin CT( 2 ). Therefore, there is a need for new imaging methods to detect bone metastases in patients with cancer. Cancer-Associated Fibroblasts are important physiological and pathological components of the tumor microenvironment; they play an important role in the remodeling of the extracellular matrix by secreting chemokines and cytokines during the development and metastasis of solid tumors. Cancer-Associated Fibroblasts express several biomarkers, such as α smooth muscle actin and fibroblast activation protein (FAP)( 3 ). FAP is a type-II integral membrane glycoprotein. While FAP expression levels are undetectable in normal cells, they increase significantly in the tissue remodeling area and tumor stroma.The detection of radiopharmaceuticals targeting FAP using molecular imaging technologies such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) is promising for the imaging of solid tumors( 4 ). In recent years, a new PET imaging model, FAPI PET, has been developed using FAP-specific inhibitors. It has been observed that 68 Ga-FAPI PET/CT has higher SUVmax values than 18 FDGPET/CT in various cancer types( 4 , 5 ). Additionally, it has been observed that 68 Ga-FAPI PET/CT is more successful in lobular breast cancer( 6 ), mucinous colon cancer, and signet cell gastric cancer, where 18 FDGPET/CT is insufficient( 7 , 8 ). A limited number of studies have compared 68 Ga-FAPI PET/CT and 18 FDGPET/CT for bone metastases. Wu et al. found more lesions and higher SUVmax values with 68 Ga-FAPI PET/CTthan with 18 FDGPET/CT in 30 patients with cancer and bone metastases( 9 ). In their systematic review, Li et al. found that although 68 Ga-FAPI PET/CT detected bone metastases more effectively than 18 FDGPET/CT, its false-positive rate could be higher( 10 ). In this study, we compared the relative performance of 68 Ga-FAPIPET/CT and 18 FDGPET/CT in detecting bone metastases in various patients with cancer and investigated the prognostic significance of 68 Ga-FAPIPET/CT SUVmax for overall survival. 2. Materials and methods 2.1 Study design This was a retrospective, image-comparative, single-center study conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants or their legal representatives. There was no external source of funding. This study was approved by the Ethics Committee of Gaziantep University Faculty of Medicine (No.2023/101). In our study, 587 patients who underwent both 68 Ga-FAPI/PET/CT and 18 FDG-PET/CT within 1 week were retrospectively scanned. Between the two PET/CT scans, the patients did not receive any treatment that could have changed the results. The PET-CT images were reported by nuclear medicine specialists in the field of PET. Patients newly diagnosed or under follow-up, aged 18 or older, with bone metastases detected on 68 Ga-FAPIPET/CT and 18 FDGPET/CT were included in the study. Those with prostate cancer undergoing PSMAPET/CT, neuroendocrine tumors undergoing DOTATATE PET/CT, hematological cancer, two known primary cancers, active arthritis, chronic inflammatory disease, and cirrhosis were excluded from the study. 2.2 18 FDGPET/CT and 68 Ga-FAPI PET/CT imaging protocols and definitions After a 12 hour fast, blood sugar levels were measured. Patients with blood glucose levels < 150 mg/dL received intravenous(IV) injection of 5 MBq/Kg 18 FDG. One hour after the injection, PET/CT scan was conducted at our center using the GE Discovery IQ; BGO, 5 Ring, 16 Slice combined PET/CT device (General Electric Company, Milwaukee, Wisconsin, USA). PET/CT scan was performed as whole-body imaging from the vertex to the upper part of the femur. 68 Ga-FAPI-04 was synthesized and labelled in a modular laboratory (Modular Lab-Easy; Eckert & Ziegler). At the end of the 1-hour preparation process, a 60–70% radiochemical yield was obtained. Control by TLC and HPLC revealed that the radiochemical purity was > 98%. The synthesized 68 Ga-DOTA-FAPI-04 was injected into the patient at a dose of 2–3 MBq/kg. Forty-five minutes after injection, FAPI-PET/CT was performed( 11 ). Although histopathological examination is the gold standard for detecting bone metastases, performing a bone biopsy is the final method because of its technical difficulties. Therefore, patients who were followed up clinically and radiologically for at least 3 months after PET/CT were included in this study to determine the course of the lesion. In addition, bone scintigraphy and bone MRI were performed in a limited number of patients. In total, 139 bone lesions with reported SUVmax values on both 68 Ga-FAPI PET/CT and 18 FDGPET/CT were analyzed. The lesions with or without SUVmax value and lesions observed on 68 Ga-FAPI PET/CT or 18 FDGPET/CT were counted retrospectively. In addition, we determined the lytic/sclerotic features of the lesions, localization of bone lesions, and levels of the biochemical parameters lactate dehydrogenase(LDH) and alkaline phosphatase(ALP). In PET/CT reports, the SUVmax values of bone metastases with high SUVmax values have been reported. Bone lesions indicated as metastases in the 68 Ga-FAPI PET/CT or 18 FDGPET/CT reports were counted. Overall survival (OS) was defined as the time from the date of diagnosis to the date of the last follow-up or dead. 2.3.Statistical analyses The normal distribution of the numerical variables was assessed using the Shapiro–Wilk test. Categorical data were represented numerically as percentages. Continuous variables are expressed as mean standard deviation. Relationships between categorical variables were examined using the chi-square test. We used receiver operating characteristic (ROC) analysis to determine the cut-off point for SUVmax values. The Mann–Whitney U test or Kruskal–Wallis analysis was used to compare SUVmax values between subgroups. We examined the relationships between numerical variables using Spearman’s correlation analysis. The lesion detection capacities of 68 Ga-FAPI PET/CT and 18 FDGPET/CT were compared with the Wilcoxon test. The effects of SUVmax values and other possible factors on overall survival were examined with Cox regression analysis. Survival analysis of low and high SUVmax groups was performed by the Kaplan–Meier method. Analyses were carried out with SPSS version 22.0 (IBM, NY, USA). Statistical significance was set at p < 0.05. 3. Results A total of 75 eligible patients,with a median age of 55(30–83) years, were included. A total of 139 patients with metastatic bone lesions were analyzed. For each patient, the median and interquartile range(IQR) of 1( 1 – 2 ) bone lesions were assessed, and the patient cohort received a median(IQR) of 1( 1 – 2 ) lines of treatment at the time of the 68 Ga-FAPI PET/CT. Among them, 18(24%) patients were treatment-naive when undergoing 68 Ga-FAPI PET/CT. The disease subtypes, localization of bone metastases, and patient characteristics are summarized in Table-1. The median (IQR) SUVmax for the primary lesion in 68 Ga-FAPI PET/CT SUVmax median(IQR) was 10.75(6.5–15), while for 18 FDGPET/CT, it was 6.7(3.6–12). A correlation was observed between the primary lesion’s 18 FDGPET/CT SUVmax and ALP and LDH levels (rho = 0.34, p = 0.022 and rho = 0.33, p = 0.027, respectively). However, there was no correlation between the primary lesion’s 68 Ga-FAPI PET/CT SUVmax and ALP and LDH levels. There was a correlation between 68 Ga-FAPI PET/CT SUVmax values of the bone lesions and 18 FDGPET/CT SUVmax values of the bone lesions (rho:0.421, p < 0.001). Bone lesions 68 Ga-FAPI PET/CT SUVmax median(IQR) were 7.8(4.6–13.2), and the 18 FDGPET/CT SUVmax of bone lesions were 5.9(3.8–8.2). Bone metastasis was detected as a median IQR of 4( 1 – 9 ) on 68 Ga-FAPI PET/CT and a median IQR of 2( 1 – 6 ) on 18 FDGPET/CT (rho = 0.81, p = 0.014).While 298 bone lesions thought to be metastases were identified in the 18 FDGPET/CT reports, 405 were identified in the 68 Ga-FAPI PET/CT reports. A total of 107 bone lesions were not observed on 18 FDGPET/CT, but an additional lesion was observed on 68 Ga-FAPI PET/CT. There was a strong correlation between the number of bone lesions detected using 68 Ga-FAPI PET/CT and 18 FDGPET/CT (rho = 0.81, p < 0.001). There was a relationship between the number of bone lesions detected by 18 FDGPET/CT and LDH levels (p = 0.004). However, there was no relationship between the number of bone lesions detected using 68 Ga-FAPI PET/CT and LDH levels (p = 0.054). There was a moderate positive correlation between ALP and LDH values(rho:0,461, p < 0,001). There was no correlation between ALP or LDH levels and lytic, sclerotic,or mixed bone metastases(p = 0.069 and p = 0.745, respectively). Lesions seen on 68 Ga-FAPI PET/CT but not detected on 18 FDGPET/CT were often sclerotic bone lesions(p = 0.001). 68 Ga-FAPI PET/CT SUVmax and 18 FDG PET/CT SUVmax values were compared according to the location of bone lesions. 68 Ga-FAPI PET/CT SUVmax was significantly higher in vertebral and thoracic lesions (p = 0.011 and p = 0.018, respectively), but there was no difference in pelvic lesions (p = 0.093). Median SUVmax of 18 FDGPET/CT bone lesions in denovo patients was 5.4 + 3.8, and the median SUVmax of bone lesions in patients with recurrence was 7.8 + 3.7 (p = 0.036). The median SUVmax value of bone lesions in 68 Ga-FAPI PET/CT denovo patients was 10.6 + 9.2, and in patients with recurrence 9.6 + 6.6 (p = 0.504). There was no difference in 18 FDG PET/CT and 68 Ga-FAPI PET/CT SUVmax values of bone lesions according to the disease subtype (p = 0.45 and p = 0.26, respectively). 3.1 Survival analysis Breast, lung, gastrointestinal, urogenital, thyroid, and head and neck cancers were frequently observed in the study cohort. OS differed significantly according to disease subtype(p < 0.001). The median OS in female patients was 46(33–58) months and in male patients was 20(12–27) months (p < 0.001). While the median OS time in de novo patients was 21 months 95%CI(17.3–24.6), the median OS time in patients with recurrence was 46 months 95%CI(43.7–48.3) (p < 0.001). High ALP HR:1.004, 95%CI(1.002–1.006) and LDH HR:1.004, 95%CI(1.001–1.004) had a negative impact on OS (p < 0.001 and p = 0.004, respectively). As the 68 Ga-FAPI PET/CTSUVmax value of the bone lesions increased, the OS time decreased (p 7.7 was found for OS (AUC:0.619; sensitivity = 57.6%; specificity = 67.5%)( Figure-1A ). The SUVmax of 68 Ga-FAPI PET/CT bone lesions was above the cut-off in 70 lesions (50.4%) and below the cut-off in 69 lesions (49.6%). The median OS in the group above the cutoff was 32(20–43) months, and the median OS in the group below the cut-off was 45(41–48) months(p = 0.002)( Figure-1B ). In multivariate analysis, 68 Ga-FAPI PET/CT SUVmax value, disease subtype, ALP level, alkaline phosphatase level, and disease presentation (recurrence or de novo) were found to be significant factors affecting OS time( Table-2 ). Discussion In this study, the median 68 Ga-FAPI PET/CTSUVmax values were higher than the median 18 FDGPET/CT SUVmax in both primary and bone lesions. 68 Ga-FAPI PET/CT detected more bone and sclerotic lesions than 18 FDGPET/CT. Although the 68 Ga-FAPI PET/CTSUVmax value of bone lesions had a prognostic value for OS time, the 18 FDGPET/CT SUVmax value of bone lesions did not have a prognostic value. The bone is an important area of metastasis after the liver and lungs. The development of bone metastasis can be explained by excessive blood flow and the large number of growth factors in the bone( 12 ). Detecting bone metastases is important not only for patients with advanced-stage, but also for accurate staging and treatment plans in newly diagnosed patients. In our study, 107 bone lesions were detected on 68 Ga-FAPI PET/CT but not on 18 FDGPET/CT. However, the distinction between benign and malignant lesions is typically determined through histopathological analysis. Elevated FAPI/PET activity has also been observed in various benign conditions, such as fibrotic, granulomatous, scar/wound, brucellosis, degenerative diseases, inflammatory diseases, disc herniation, and bone fracture( 13 ). In our study, the 16th patient exhibited clearer visualization of bone and liver lesions with a higher SUVmax on 68 Ga-FAPI PET/CT compared to simultaneous 18 FDGPET/CT( Figure-2 ). In the 29th patient, cancerous invasive lobules with a low Ki-67 index and additional lesions in the mediastinal lymph node and bone were detected on 68 Ga-FAPI PET/CT ( Figure-3 ). In the 50th patient, while the bone lesion disappeared on 18 FDGPET/CT with treatment, it persisted on 68 Ga-FAPI PET/CT ( Figure-4 ). These examples suggest that 68 Ga-FAPI PET/CT may detect bone lesions earlier than 18 FDGPET/CT. The observation of post-treatment lesions on 68 Ga-FAPI PET/CT may be attributed to its better capability in detecting residual tumors. If 68 Ga-FAPI PET/CT can detect bone lesions earlier, it can provide more accurate staging than 18 FDGPET/CT. Randomized and confirmatory studies are required to address these issues. To our knowledge, this is the first study to investigate the prognostic importance of the bone lesions 68 Ga-FAPI PET/CT SUVmax value for survival in patients with bone lesions. In a study by Wu et al.,the performances of 68 Ga-FAPI PET/CT and 18 FDGPET/CT were compared in 30 patients with cancer and bone metastases, with a focus on lung, thyroid, liver, and prostate cancer. However, the effect of 68 Ga-FAPI PET/CT SUVmax value on survival was not examined( 9 ). A systematic review by Li et al. analyzed the bone metastasis subgroups of studies comparing 68 Ga-FAPI PET/CT and 18 FDG PET/CT. Nevertheless, the total number of patients with bone metastases was 67. In our study, out of the 75 patients included, 44% had breast cancer, followed by lung, gastrointestinal tract, urogenital tract, and thyroid cancers. The higher female-to-male ratio was influenced by the proportion of patients with breast cancer, and the overall survival of female patients was significantly longer,reflecting the favorable prognosis of breast cancer. Our study revealed a correlation between 18 FDGPET/CT SUVmax value and ALP and LDH values. However,no such correlation was observed between 68 Ga-FAPI PET/CT findings and ALP or LDH levels. In general, the 18 FDGPET/CT SUVmax value indicates high metabolic activity of the tumor, and LDH may be highly correlated with the tumor burden( 14 ).Cancer-related fibroblasts and fibroblast activation proteins, which are involved in FAPI PET imaging, are microenvironmental elements; therefore, 68 Ga-FAPI PET/CTSUVmax and metabolic markers may not be associated( 13 ). In our study, ALP and LDH levels significantly affect OS duration, potentially reflecting the disease burden and presence of other organ metastases in our patient cohort. Consistent with our results, previous research has demonstrated that elevated LDH and ALP predict a poorer prognosis for survival in patients with various cancers( 15 ). In our study, two-thirds of the bone lesions detected on 68 Ga-FAPI PET/CT but not on 18 FDGPET/CT were sclerotic.This observation may be relevant, especially in diseases such as breast and prostate cancer that progress with sclerotic bone metastases. Previous studies have highlighted the high diagnostic value of 18 FDG PET/CT in detecting bone metastases, while MRI exhibits high specificity but low sensitivity for this purpose( 16 ). In our study, 68 Ga-FAPI PET/CT detected more bone lesions and had a higher SUVmax than 18 FDG PET/CT in the cranium, vertebra, thorax, pelvis, and extremities. Significant differences were observed between the two modalities in terms of the SUVmax values of vertebral and thoracic lesions (p = 0.011 and p = 0.018, respectively). Moreover, we analyzed the parameters that could possibly affect survival. The disease subtype of the patients in the cohort was a parameter affecting the OS. As it is known in database studies, OS times of stage-4 breast and lung cancers are significantly different( 17 ). High levels of ALP and LDH in biochemical tests affected OS. Since ALP and LDH levels were in similar groups, ALP was included in the Cox-regression model(p < 0.001 and P = 0.004, respectively). In our study, the OS of patients with recurrent metastasis was significantly longer than that of patients with de novo metastasis. This may be because in our cohort some patients were diagnosed at an early stage and received curative treatment. Additionally, in cancers such as lung and pancreatic, the survival of patients with recurrent metastasisis longer than that of de novo patients( 18 , 19 ). In our study, another important factor affecting OS was 68 Ga-FAPI PET/CT SUVmax of bone lesions. An important finding was that the 18 FDG PET/CT SUVmax value of bone lesions was not a factor affecting OS in the same patient cohort. In previous studies, the prognostic significance of the 18 FDGPET/CT SUVmax value in patients with bone metastases due to breast cancer was not observed( 20 ). In our multivariate analysis performed for OS, we observed that the 68 Ga-FAPI PET/CT SUVmax value of bone lesions was a parameter as important as the cancer subtype. Our study has some limitations:( 1 ) its retrospective design and the relatively limited number of patients, including both de novo and with recurrence, and different cancer diagnoses;( 2 )the histopathology of the bone lesions was not confirmed due to the absence of bone biopsy;and ( 3 ) we did not perform a detailed lesion analysis, and only reported or mentioned lesions were analyzed. Nevertheless, our study is one of the few on this subject and reveals the prognostic importance of the 68 Ga-FAPI PET/CT SUVmax value. Moreover, the bone lesions included were those observed on both 68 Ga-FAPI PET/CT and 18 FDGPET/CT and were most likely bone metastases. In conclusion, in patients with bone lesions due to various cancers, 68 Ga-FAPI PET/CT detects more lesions and at higher SUVmax values than 18 FDGPET/CT. 68 Ga-FAPI PET/CT additionally detects sclerotic bone lesions that are not usually detected in 18 FDGPET/CT. As the 68 Ga-FAPI PET/CT SUVmax value of the bone lesions increased, the overall survival time of the patients decreased. The prognostic value of 18 FDGPET/CT SUVmax value of bone lesions was not observed in the same patient group. The results of our study need to be confirmed in a more homogeneous patient group with lesions with histological confirmation and in studies involving more patients. Declarations Funding: This research received no external funding. Conflict of interests: The authors have no conflict of interests to declare regarding the publication of this paper. References Coleman RE, Croucher PI, Padhani AR, et al. Bone metastases. Nat Rev Dis Primers. 2020;6:83. Michael HY, Hoffe SSE, Abrahm J, Pollock RE, Kheterpal A. Epidemiology, clinical presentation, and diagnosis of bone metastasis in adults. 2019. Fitzgerald AA, Weiner LM. The role of fibroblast activation protein in health and malignancy. Cancer Metastasis Rev. 2020;39:783–803. Dong Y, Zhou H, Alhaskawi A et al. The Superiority of Fibroblast Activation Protein Inhibitor (FAPI) PET/CT Versus FDG PET/CT in the Diagnosis of Various Malignancies. Cancers (Basel) 2023;15. Guglielmo P, Alongi P, Baratto L et al. Head-to-Head Comparison of FDG and Radiolabeled FAPI PET: A Systematic Review of the Literature. Life (Basel) 2023;13. Eshet Y, Tau N, Apter S, et al. The Role of 68 Ga-FAPI PET/CT in Detection of Metastatic Lobular Breast Cancer. Clin Nucl Med. 2023;48:228–32. Kömek H, Can C, Kaplan İ, et al. Comparison of [(68) Ga]Ga-DOTA-FAPI-04 PET/CT and [(18)F]FDG PET/CT in colorectal cancer. Eur J Nucl Med Mol Imaging. 2022;49:3898–909. Chen H, Pang Y, Li J, et al. Comparison of [(68)Ga]Ga-FAPI and [(18)F]FDG uptake in patients with gastric signet-ring-cell carcinoma: a multicenter retrospective study. Eur Radiol. 2023;33:1329–41. Wu J, Wang Y, Liao T, et al. Comparison of the Relative Diagnostic Performance of [(68)Ga]Ga-DOTA-FAPI-04 and [(18)F]FDG PET/CT for the Detection of Bone Metastasis in Patients With Different Cancers. Front Oncol. 2021;11:737827. Li L, Hu X, Ma J, Yang S, Gong W, Zhang C. A systematic review of [(68)Ga]Ga-DOTA-FAPI-04 and [(18)F]FDG PET/CT in the diagnostic value of malignant tumor bone metastasis. Front Oncol. 2022;12:978506. Şahin E, Elboğa U, Çelen YZ, Sever ÖN, Çayırlı YB, Çimen U. Comparison of (68)Ga-DOTA-FAPI and (18)FDG PET/CT imaging modalities in the detection of liver metastases in patients with gastrointestinal system cancer. Eur J Radiol. 2021;142:109867. Roodman GD. Mechanisms of Bone Metastasis. N Engl J Med. 2004;350:1655–64. Dondi F, Albano D, Treglia G, Bertagna F. Emerging Role of FAPI PET Imaging for the Assessment of Benign Bone and Joint Diseases. J Clin Med 2022;11. Giesen N, Sprute R, Rüthrich M, et al. Evidence-based management of COVID-19 in cancer patients: Guideline by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO). Eur J Cancer. 2020;140:86–104. Ji F, Fu SJ, Guo ZY, et al. Prognostic value of combined preoperative lactate dehydrogenase and alkaline phosphatase levels in patients with resectable pancreatic ductal adenocarcinoma. Med (Baltim). 2016;95:e4065. Qu X, Huang X, Yan W, Wu L, Dai K. A meta-analysis of ¹⁸FDG-PET-CT, ¹⁸FDG-PET, MRI and bone scintigraphy for diagnosis of bone metastases in patients with lung cancer. Eur J Radiol. 2012;81:1007–15. Gross-Erne M, Zimmerli L, Bassetti S, Li Q, Feller A, Mingrone W. A long-term retrospective observational study at a medium-sized medical oncology service in Switzerland: comparison of overall survival with a national cohort and adherence to treatment guidelines. Swiss Med Wkly. 2023;153:40091. Moore S, Leung B, Wu J, Ho C. Survival Implications of De Novo Versus Recurrent Metastatic Non–Small Cell Lung Cancer. Am J Clin Oncol. 2019;42:292–7. Miotke L, Nevala-Plagemann C, Ying J, Florou V, Haaland B, Garrido-Laguna I. Treatment outcomes in recurrent versus de novo metastatic pancreatic adenocarcinoma: a real world study. BMC Cancer. 2022;22:1054. Peterson LM, O'Sullivan J, Wu QV, et al. Prospective Study of Serial (18)F-FDG PET and (18)F-Fluoride PET to Predict Time to Skeletal-Related Events, Time to Progression, and Survival in Patients with Bone-Dominant Metastatic Breast Cancer. J Nucl Med. 2018;59:1823–30. Tables Table-1 :Baseline characteristics of the patients Parameters Age, median, (range), years 55 (30–83) Gender, n(%) Female Male 46(61,3) 29(38,7) Lesion character, n(%) Lytic Sclerotic Mixed. 42(30,2) 81(58,3) 16(11,5) Localization of bone Metastasis, n(%) Cranium Vertebra Upper limb Thorax Pelvis Lower limb 7(5) 41(29,5) 3(2,2) 31(22,3) 43(30,9) 14(10,1) Inspection purpose, n(%). Newly diagnosed Suspected recurrence or progression 48(64) 27(36) Disease type, n(%). Breast cancer Lung cancer Gastrointestinal cancers Urogenital cancers Thyroid cancer Other cancers 33(44) 12(16) 10(13,3) 6(8) 4(5,3) 10(13,3) Table-2 : Univariable and multivariable analysis of factors affecting overall survival Parameters Univariable Multivariable HR (95% CI) p value HR (95% CI) p value Gender 0.380(0.252–0.574) <0.001 0.437 Bone lesion FDG-PET SUVmax 1.06(0.99–1.12) 0.079 Bone lesion FAPI-PET SUVmax 1.047(1.021–1.075) <0.001 1.03(1.01–1.06) 0.012 Disease presentation (recurrence versus de novo) 3.29(2.11–5.13) <0.001 2.56(1.50–4.39) 0.001 Lesion type (lytic versus sclerotic) 2.10(0.99–4.43) 0.064 Disease subtype (breast versus lung cancer) 0.95(0.48–1.88) <0.001 0.74(0.27–2.00) 0.001 Alkaline phosphatase 1.004(1.002–1.005) <0.001 1.004(1.002–1.006) 0.001 Cite Share Download PDF Status: Published Journal Publication published 30 Apr, 2024 Read the published version in Annals of Nuclear Medicine → Version 1 posted Reviewers agreed at journal 28 Feb, 2024 Reviewers invited by journal 20 Feb, 2024 Editor assigned by journal 19 Feb, 2024 First submitted to journal 19 Feb, 2024 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. 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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-3973887","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":274218460,"identity":"4cb882c2-3d8f-41b2-a4cc-934a06b2ec45","order_by":0,"name":"HACI ARAK","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYBACAyBmbKiokTOAcC2I1XLmmLEBAzOIK0GklsYW5sQNYC0MRGgxZz/78OPMBrb07ez9Rzf8KJBg4G/vTsCrxbIn3Vhy4w6Z3J09h9lu9gAdJnHm7Ab8DjuQxiD58Axb7oYbyWw3eIBaDCRyCWg5/4z558M25nQDoJabf4jSciONTXJjG3MCSMtt4my58YzNcsaZY4Ybzhw2uy1jIMFD2C/n05hv9lTUyBscb3x2880fGzn+9l78WjAAD2nKR8EoGAWjYBRgBQA61UohW483DwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-2023-423X","institution":"Gaziantep city hospital,, Department of Medical Oncology","correspondingAuthor":true,"prefix":"","firstName":"HACI","middleName":"","lastName":"ARAK","suffix":""},{"id":274218461,"identity":"ac1d678f-ee3a-45ad-835a-d45af82ae49b","order_by":1,"name":"Umut Elboga","email":"","orcid":"","institution":"Gaziantep University Şahinbey Training and Research Hospital, Department of nuclear medicine","correspondingAuthor":false,"prefix":"","firstName":"Umut","middleName":"","lastName":"Elboga","suffix":""},{"id":274218462,"identity":"f0fec765-975d-4de1-9aab-39c1cc0ec668","order_by":2,"name":"Yusuf Burak Cayırlı","email":"","orcid":"","institution":"Department of nuclear medicine, Gaziantep University Şahinbey Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yusuf","middleName":"Burak","lastName":"Cayırlı","suffix":""},{"id":274218463,"identity":"6199ebdd-d1cf-4154-9bd8-01f7705ed439","order_by":3,"name":"Aydın Aytekin","email":"","orcid":"","institution":"Department of Medical Oncology, Gaziantep University Şahinbey Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Aydın","middleName":"","lastName":"Aytekin","suffix":""}],"badges":[],"createdAt":"2024-02-20 21:38:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3973887/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3973887/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s12149-024-01935-3","type":"published","date":"2024-04-30T19:57:41+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":51564869,"identity":"dc669181-fcd9-4883-9221-ee286c077cda","added_by":"auto","created_at":"2024-02-23 18:58:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":21763,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e) In the ROC analysis for overall survival \u003csup\u003e68\u003c/sup\u003eFAPI-PET/CT SUVmax cutoff value of 7.7 was found (AUC: 0.619).\u003cstrong\u003eB\u003c/strong\u003e) The overall survival of patients with FAPI-PET-CT SUVmax value above and below 7.7 was significantly different in Kaplan-Maier analysis (p = 0.002).\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3973887/v1/cecbcfce48a1a7881f479439.png"},{"id":51565773,"identity":"d284b644-23bc-49c3-b621-2e2b4b11d36c","added_by":"auto","created_at":"2024-02-23 19:06:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":773569,"visible":true,"origin":"","legend":"\u003cp\u003eThe patient is 34 years old, estrogen receptor 95% positive,CerbB-2 negative, Ki-67: 15%, and was operated after neoadjuvant chemotherapy (ypT3N2M0). After intake oftamoxifen and goseelin for 2–3 years, recurrence with bone and liver lesions developed.\u003cstrong\u003e1.a\u003c/strong\u003e: left iliac bone lesion FDG-PET (SUVmax: 7). \u003cstrong\u003e2.a\u003c/strong\u003e: left iliac bone lesion FAPI-PET(SUVmax:11). \u003cstrong\u003e1.b\u003c/strong\u003e: FDG-PET at the lower end of the sacrum (SUVmax: 3.9). \u003cstrong\u003e2.b\u003c/strong\u003e: FAPI-PET at the lower end of the sacrum (SUVmax: 9.1). \u003cstrong\u003e1.c\u003c/strong\u003e: liver metastatic lesions FDG-PET (SUVmax: 5, 9).\u003cstrong\u003e2.c\u003c/strong\u003e: liver lesions FAPI-PET (SUVmax:17.2).\u003c/p\u003e","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-3973887/v1/f857e1927839ac91fdf0a77e.png"},{"id":51564872,"identity":"a1f84b3e-4347-492d-94bd-f29c95b86924","added_by":"auto","created_at":"2024-02-23 18:58:53","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":492601,"visible":true,"origin":"","legend":"\u003cp\u003eThe patient received treatment for invasive lobular breast cancer in the left breast 13 years ago. She was diagnosed with invasive lobular cancer in the right breast 2 years ago. Estrogen was 100%, progesterone was 10% and CerbB2 was negative, Ki-67: 5%. \u003csup\u003e68\u003c/sup\u003eFAPI-PET/CT revealed bone and mediastinal lymph node metastases in addition to the mass in the right breast.\u003cstrong\u003e1.a\u003c/strong\u003e. Primary lesion in the right breast FDG-PET/CT (SUVmax:3.2). Mediastinal lymph nodes are normometabolic. \u003cstrong\u003e2.a.\u003c/strong\u003e Right breast primary lesion in FAPI-PET/CT (SUVmax: 21.8), hypermetabolic metastatic lymph nodes in the mediastinum in FAPI-PET/CT (subcarinal SUVmax: 11.2, retrosternal SUVmax: 5.8). \u003cstrong\u003e1.b.\u003c/strong\u003e Normometabolic lesion in the right acetabulum on FDG-PET/CT. \u003cstrong\u003e2.b\u003c/strong\u003e. Bone lesion in the right acetabulum FAPI-PET/CT (SUVmax: 5.8).\u003c/p\u003e","description":"","filename":"figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-3973887/v1/6b60bdfac676eae529ecf28b.png"},{"id":51564871,"identity":"08d450a2-2261-480b-aae4-75eb3178b1fe","added_by":"auto","created_at":"2024-02-23 18:58:53","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":834123,"visible":true,"origin":"","legend":"\u003cp\u003eThe patient was diagnosed with de novo metastatic breast cancer at the age of 39. After receiving ribociclib, letrozole, and goserelin treatment for 3 months, simultaneous FAPI-PET and FDG-PET were performed. Significant SUVmax values are still present after treatment on FAPI-PET imaging.\u003cstrong\u003e1.a\u003c/strong\u003e. There is mild FDG uptake in the axillary lymph node. \u003cstrong\u003e2.a.\u003c/strong\u003e Axillary lymph node in \u003csup\u003e\u003cstrong\u003e6\u003c/strong\u003e\u003c/sup\u003e\u003csup\u003e8\u003c/sup\u003eFAPI –PET/CT (SUVmax: 6.7).\u003cstrong\u003e1.b\u003c/strong\u003e. Left breast primary mass FDG-PET (SUVmax:3.2). \u003cstrong\u003e2.b\u003c/strong\u003e. Left breast primary mass \u003csup\u003e\u003cstrong\u003e6\u003c/strong\u003e\u003c/sup\u003e\u003csup\u003e8\u003c/sup\u003eFAPI-PET/CT (SUVmax:10.3). \u003cstrong\u003e1.c\u003c/strong\u003e. L4 vertebra \u003csup\u003e\u003cstrong\u003e18\u003c/strong\u003e\u003c/sup\u003eFDG-PET/CT sclerotic lesion. \u003cstrong\u003e2.c\u003c/strong\u003e. Hypermetabolic lesion in L4 vertebra on 68FAPI-PET/CT (SUVmax:15). \u003cstrong\u003e3.a\u003c/strong\u003e. MRI sagittal section shows lesions compatible with metastasis in the thoracic-lumbar vertebrae. \u003cstrong\u003e3.b\u003c/strong\u003e. Metastatic lesion in L4 vertebra, MRI transverse section.\u003c/p\u003e","description":"","filename":"figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-3973887/v1/f80d348420d2b503a78265e9.png"},{"id":56043156,"identity":"b266662c-164f-4648-bc2d-9b490203715b","added_by":"auto","created_at":"2024-05-07 20:10:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2524917,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3973887/v1/c4dd87a3-495b-4bea-8f8b-04605691e1af.pdf"}],"financialInterests":"","formattedTitle":"Prognostic significance of 68Ga-FAPI-PET/CT in patients with bone metastases in various cancers","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eBone metastasis is common in certain advanced-stage cancers, particularly in prostate, breast, lung, thyroid, renal cell, gynecologic, and melanoma cancers. The occurrence of skeletal-related events, including pain, pathological fractures, hypercalcemia, and spinal cord compression, is a common consequence of bone metastases. Skeletal events negatively affect the quality of life of patients with cancer(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Therefore, early and accurate detection of bone metastases is crucial, both during the initial diagnosis and recurrence. Radiography, technetium-99m (Tc-99m) skeletal scintigraphy, computed tomography (CT), magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose-positron emission tomography (\u003csup\u003e18\u003c/sup\u003eF-FDGPET) can be used to detect bone metastases. However, these methods have limitations. Radiography exhibits low sensitivity and specificity, while bone scintigraphy allows for limited detection of lytic lesions. \u003csup\u003e18\u003c/sup\u003eFDGPET/CT may yield inaccurate results in cases of infection, arthritis, and benign bone lesions. CT and MRI are unsuitable for whole-body bone scans,and there are technical challenges in MRI, along with nephrotoxic side effects of contrast solutionsin CT(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Therefore, there is a need for new imaging methods to detect bone metastases in patients with cancer.\u003c/p\u003e \u003cp\u003eCancer-Associated Fibroblasts are important physiological and pathological components of the tumor microenvironment; they play an important role in the remodeling of the extracellular matrix by secreting chemokines and cytokines during the development and metastasis of solid tumors. Cancer-Associated Fibroblasts express several biomarkers, such as α smooth muscle actin and fibroblast activation protein (FAP)(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). FAP is a type-II integral membrane glycoprotein. While FAP expression levels are undetectable in normal cells, they increase significantly in the tissue remodeling area and tumor stroma.The detection of radiopharmaceuticals targeting FAP using molecular imaging technologies such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) is promising for the imaging of solid tumors(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn recent years, a new PET imaging model, FAPI PET, has been developed using FAP-specific inhibitors. It has been observed that\u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT has higher SUVmax values than \u003csup\u003e18\u003c/sup\u003eFDGPET/CT in various cancer types(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Additionally, it has been observed that \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT is more successful in lobular breast cancer(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), mucinous colon cancer, and signet cell gastric cancer, where \u003csup\u003e18\u003c/sup\u003eFDGPET/CT is insufficient(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). A limited number of studies have compared \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT and \u003csup\u003e18\u003c/sup\u003eFDGPET/CT for bone metastases. Wu et al. found more lesions and higher SUVmax values with \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CTthan with \u003csup\u003e18\u003c/sup\u003eFDGPET/CT in 30 patients with cancer and bone metastases(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). In their systematic review, Li et al. found that although \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT detected bone metastases more effectively than \u003csup\u003e18\u003c/sup\u003eFDGPET/CT, its false-positive rate could be higher(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this study, we compared the relative performance of \u003csup\u003e68\u003c/sup\u003eGa-FAPIPET/CT and \u003csup\u003e18\u003c/sup\u003eFDGPET/CT in detecting bone metastases in various patients with cancer and investigated the prognostic significance of \u003csup\u003e68\u003c/sup\u003eGa-FAPIPET/CT SUVmax for overall survival.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study design\u003c/h2\u003e \u003cp\u003e This was a retrospective, image-comparative, single-center study conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants or their legal representatives. There was no external source of funding. This study was approved by the Ethics Committee of Gaziantep University Faculty of Medicine (No.2023/101).\u003c/p\u003e \u003cp\u003eIn our study, 587 patients who underwent both \u003csup\u003e68\u003c/sup\u003eGa-FAPI/PET/CT and \u003csup\u003e18\u003c/sup\u003eFDG-PET/CT within 1 week were retrospectively scanned. Between the two PET/CT scans, the patients did not receive any treatment that could have changed the results. The PET-CT images were reported by nuclear medicine specialists in the field of PET. Patients newly diagnosed or under follow-up, aged 18 or older, with bone metastases detected on \u003csup\u003e68\u003c/sup\u003eGa-FAPIPET/CT and \u003csup\u003e18\u003c/sup\u003eFDGPET/CT were included in the study. Those with prostate cancer undergoing PSMAPET/CT, neuroendocrine tumors undergoing DOTATATE PET/CT, hematological cancer, two known primary cancers, active arthritis, chronic inflammatory disease, and cirrhosis were excluded from the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2\u003csup\u003e18\u003c/sup\u003eFDGPET/CT and \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT imaging protocols and definitions\u003c/h2\u003e \u003cp\u003eAfter a 12 hour fast, blood sugar levels were measured. Patients with blood glucose levels\u0026thinsp;\u0026lt;\u0026thinsp;150 mg/dL received intravenous(IV) injection of 5 MBq/Kg \u003csup\u003e18\u003c/sup\u003eFDG. One hour after the injection, PET/CT scan was conducted at our center using the GE Discovery IQ; BGO, 5 Ring, 16 Slice combined PET/CT device (General Electric Company, Milwaukee, Wisconsin, USA). PET/CT scan was performed as whole-body imaging from the vertex to the upper part of the femur.\u003c/p\u003e \u003cp\u003e \u003csup\u003e68\u003c/sup\u003eGa-FAPI-04 was synthesized and labelled in a modular laboratory (Modular Lab-Easy; Eckert \u0026amp; Ziegler). At the end of the 1-hour preparation process, a 60\u0026ndash;70% radiochemical yield was obtained. Control by TLC and HPLC revealed that the radiochemical purity was \u0026gt;\u0026thinsp;98%. The synthesized \u003csup\u003e68\u003c/sup\u003eGa-DOTA-FAPI-04 was injected into the patient at a dose of 2\u0026ndash;3 MBq/kg. Forty-five minutes after injection, FAPI-PET/CT was performed(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough histopathological examination is the gold standard for detecting bone metastases, performing a bone biopsy is the final method because of its technical difficulties. Therefore, patients who were followed up clinically and radiologically for at least 3 months after PET/CT were included in this study to determine the course of the lesion. In addition, bone scintigraphy and bone MRI were performed in a limited number of patients. In total, 139 bone lesions with reported SUVmax values on both \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT and \u003csup\u003e18\u003c/sup\u003eFDGPET/CT were analyzed. The lesions with or without SUVmax value and lesions observed on \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT or \u003csup\u003e18\u003c/sup\u003eFDGPET/CT were counted retrospectively. In addition, we determined the lytic/sclerotic features of the lesions, localization of bone lesions, and levels of the biochemical parameters lactate dehydrogenase(LDH) and alkaline phosphatase(ALP).\u003c/p\u003e \u003cp\u003eIn PET/CT reports, the SUVmax values of bone metastases with high SUVmax values have been reported. Bone lesions indicated as metastases in the \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT or\u003csup\u003e18\u003c/sup\u003eFDGPET/CT reports were counted. Overall survival (OS) was defined as the time from the date of diagnosis to the date of the last follow-up or dead.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3.Statistical analyses\u003c/h2\u003e \u003cp\u003eThe normal distribution of the numerical variables was assessed using the Shapiro\u0026ndash;Wilk test. Categorical data were represented numerically as percentages. Continuous variables are expressed as mean standard deviation. Relationships between categorical variables were examined using the chi-square test. We used receiver operating characteristic (ROC) analysis to determine the cut-off point for SUVmax values. The Mann\u0026ndash;Whitney U test or Kruskal\u0026ndash;Wallis analysis was used to compare SUVmax values between subgroups. We examined the relationships between numerical variables using Spearman\u0026rsquo;s correlation analysis. The lesion detection capacities of \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT and \u003csup\u003e18\u003c/sup\u003eFDGPET/CT were compared with the Wilcoxon test. The effects of SUVmax values and other possible factors on overall survival were examined with Cox regression analysis. Survival analysis of low and high SUVmax groups was performed by the Kaplan\u0026ndash;Meier method. Analyses were carried out with SPSS version 22.0 (IBM, NY, USA). Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eA total of 75 eligible patients,with a median age of 55(30–83) years, were included. A total of 139 patients with metastatic bone lesions were analyzed. For each patient, the median and interquartile range(IQR) of 1(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) bone lesions were assessed, and the patient cohort received a median(IQR) of 1(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) lines of treatment at the time of the\u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT. Among them, 18(24%) patients were treatment-naive when undergoing\u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT. The disease subtypes, localization of bone metastases, and patient characteristics are summarized in Table-1.\u003c/p\u003e \u003cp\u003eThe median (IQR) SUVmax for the primary lesion in \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax median(IQR) was 10.75(6.5–15), while for \u003csup\u003e18\u003c/sup\u003eFDGPET/CT, it was 6.7(3.6–12). A correlation was observed between the primary lesion’s \u003csup\u003e18\u003c/sup\u003eFDGPET/CT SUVmax and ALP and LDH levels (rho = 0.34, p = 0.022 and rho = 0.33, p = 0.027, respectively). However, there was no correlation between the primary lesion’s \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax and ALP and LDH levels.\u003c/p\u003e \u003cp\u003eThere was a correlation between \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax values of the bone lesions and \u003csup\u003e18\u003c/sup\u003eFDGPET/CT SUVmax values of the bone lesions (rho:0.421, p \u0026lt; 0.001). Bone lesions \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax median(IQR) were 7.8(4.6–13.2), and the\u003csup\u003e18\u003c/sup\u003eFDGPET/CT SUVmax of bone lesions were 5.9(3.8–8.2).\u003c/p\u003e \u003cp\u003eBone metastasis was detected as a median IQR of 4(\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7 CR8\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) on \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT and a median IQR of 2(\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) on \u003csup\u003e18\u003c/sup\u003eFDGPET/CT (rho = 0.81, p = 0.014).While 298 bone lesions thought to be metastases were identified in the \u003csup\u003e18\u003c/sup\u003eFDGPET/CT reports, 405 were identified in the \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT reports. A total of 107 bone lesions were not observed on \u003csup\u003e18\u003c/sup\u003eFDGPET/CT, but an additional lesion was observed on \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT. There was a strong correlation between the number of bone lesions detected using\u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT and \u003csup\u003e18\u003c/sup\u003eFDGPET/CT (rho = 0.81, p \u0026lt; 0.001). There was a relationship between the number of bone lesions detected by \u003csup\u003e18\u003c/sup\u003eFDGPET/CT and LDH levels (p = 0.004). However, there was no relationship between the number of bone lesions detected using \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT and LDH levels (p = 0.054).\u003c/p\u003e \u003cp\u003eThere was a moderate positive correlation between ALP and LDH values(rho:0,461, p \u0026lt; 0,001). There was no correlation between ALP or LDH levels and lytic, sclerotic,or mixed bone metastases(p = 0.069 and p = 0.745, respectively). Lesions seen on \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT but not detected on \u003csup\u003e18\u003c/sup\u003eFDGPET/CT were often sclerotic bone lesions(p = 0.001). \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax and \u003csup\u003e18\u003c/sup\u003eFDG PET/CT SUVmax values were compared according to the location of bone lesions. \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax was significantly higher in vertebral and thoracic lesions (p = 0.011 and p = 0.018, respectively), but there was no difference in pelvic lesions (p = 0.093).\u003c/p\u003e \u003cp\u003eMedian SUVmax of \u003csup\u003e18\u003c/sup\u003eFDGPET/CT bone lesions in denovo patients was 5.4 + 3.8, and the median SUVmax of bone lesions in patients with recurrence was 7.8 + 3.7 (p = 0.036). The median SUVmax value of bone lesions in \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT denovo patients was 10.6 + 9.2, and in patients with recurrence 9.6 + 6.6 (p = 0.504). There was no difference in \u003csup\u003e18\u003c/sup\u003eFDG PET/CT and \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax values of bone lesions according to the disease subtype (p = 0.45 and p = 0.26, respectively).\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Survival analysis\u003c/h2\u003e \u003cp\u003eBreast, lung, gastrointestinal, urogenital, thyroid, and head and neck cancers were frequently observed in the study cohort. OS differed significantly according to disease subtype(p \u0026lt; 0.001). The median OS in female patients was 46(33–58) months and in male patients was 20(12–27) months (p \u0026lt; 0.001). While the median OS time in de novo patients was 21 months 95%CI(17.3–24.6), the median OS time in patients with recurrence was 46 months 95%CI(43.7–48.3) (p \u0026lt; 0.001). High ALP HR:1.004, 95%CI(1.002–1.006) and LDH HR:1.004, 95%CI(1.001–1.004) had a negative impact on OS (p \u0026lt; 0.001 and p = 0.004, respectively).\u003c/p\u003e \u003cp\u003eAs the \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CTSUVmax value of the bone lesions increased, the OS time decreased (p \u0026lt; 0.001). There was no significant relationship between \u003csup\u003e18\u003c/sup\u003eFDGPET/CT SUVmax and OS time (p = 0.079). In ROC analysis, a cut-off value of \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CTSUVmax \u0026gt; 7.7 was found for OS (AUC:0.619; sensitivity = 57.6%; specificity = 67.5%)(\u003cb\u003eFigure-1A\u003c/b\u003e). The SUVmax of \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT bone lesions was above the cut-off in 70 lesions (50.4%) and below the cut-off in 69 lesions (49.6%). The median OS in the group above the cutoff was 32(20–43) months, and the median OS in the group below the cut-off was 45(41–48) months(p = 0.002)(\u003cb\u003eFigure-1B\u003c/b\u003e). In multivariate analysis, \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax value, disease subtype, ALP level, alkaline phosphatase level, and disease presentation (recurrence or de novo) were found to be significant factors affecting OS time(\u003cb\u003eTable-2\u003c/b\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, the median \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CTSUVmax values were higher than the median \u003csup\u003e18\u003c/sup\u003eFDGPET/CT SUVmax in both primary and bone lesions. \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT detected more bone and sclerotic lesions than \u003csup\u003e18\u003c/sup\u003eFDGPET/CT. Although the \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CTSUVmax value of bone lesions had a prognostic value for OS time, the \u003csup\u003e18\u003c/sup\u003eFDGPET/CT SUVmax value of bone lesions did not have a prognostic value.\u003c/p\u003e\u003cp\u003eThe bone is an important area of metastasis after the liver and lungs. The development of bone metastasis can be explained by excessive blood flow and the large number of growth factors in the bone(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Detecting bone metastases is important not only for patients with advanced-stage, but also for accurate staging and treatment plans in newly diagnosed patients. In our study, 107 bone lesions were detected on \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT but not on \u003csup\u003e18\u003c/sup\u003eFDGPET/CT. However, the distinction between benign and malignant lesions is typically determined through histopathological analysis. Elevated FAPI/PET activity has also been observed in various benign conditions, such as fibrotic, granulomatous, scar/wound, brucellosis, degenerative diseases, inflammatory diseases, disc herniation, and bone fracture(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). In our study, the 16th patient exhibited clearer visualization of bone and liver lesions with a higher SUVmax on \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT compared to simultaneous \u003csup\u003e18\u003c/sup\u003eFDGPET/CT(\u003cb\u003eFigure-2\u003c/b\u003e). In the 29th patient, cancerous invasive lobules with a low Ki-67 index and additional lesions in the mediastinal lymph node and bone were detected on\u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT (\u003cb\u003eFigure-3\u003c/b\u003e). In the 50th patient, while the bone lesion disappeared on \u003csup\u003e18\u003c/sup\u003eFDGPET/CT with treatment, it persisted on \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT (\u003cb\u003eFigure-4\u003c/b\u003e). These examples suggest that \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT may detect bone lesions earlier than \u003csup\u003e18\u003c/sup\u003eFDGPET/CT. The observation of post-treatment lesions on \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT may be attributed to its better capability in detecting residual tumors. If \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT can detect bone lesions earlier, it can provide more accurate staging than \u003csup\u003e18\u003c/sup\u003eFDGPET/CT. Randomized and confirmatory studies are required to address these issues.\u003c/p\u003e\u003cp\u003eTo our knowledge, this is the first study to investigate the prognostic importance of the bone lesions \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax value for survival in patients with bone lesions. In a study by Wu et al.,the performances of \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT and \u003csup\u003e18\u003c/sup\u003eFDGPET/CT were compared in 30 patients with cancer and bone metastases, with a focus on lung, thyroid, liver, and prostate cancer. However, the effect of \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax value on survival was not examined(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). A systematic review by Li et al. analyzed the bone metastasis subgroups of studies comparing \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT and \u003csup\u003e18\u003c/sup\u003eFDG PET/CT. Nevertheless, the total number of patients with bone metastases was 67. In our study, out of the 75 patients included, 44% had breast cancer, followed by lung, gastrointestinal tract, urogenital tract, and thyroid cancers. The higher female-to-male ratio was influenced by the proportion of patients with breast cancer, and the overall survival of female patients was significantly longer,reflecting the favorable prognosis of breast cancer.\u003c/p\u003e\u003cp\u003eOur study revealed a correlation between \u003csup\u003e18\u003c/sup\u003eFDGPET/CT SUVmax value and ALP and LDH values. However,no such correlation was observed between \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT findings and ALP or LDH levels. In general, the \u003csup\u003e18\u003c/sup\u003eFDGPET/CT SUVmax value indicates high metabolic activity of the tumor, and LDH may be highly correlated with the tumor burden(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).Cancer-related fibroblasts and fibroblast activation proteins, which are involved in FAPI PET imaging, are microenvironmental elements; therefore,\u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CTSUVmax and metabolic markers may not be associated(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). In our study, ALP and LDH levels significantly affect OS duration, potentially reflecting the disease burden and presence of other organ metastases in our patient cohort. Consistent with our results, previous research has demonstrated that elevated LDH and ALP predict a poorer prognosis for survival in patients with various cancers(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In our study, two-thirds of the bone lesions detected on \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT but not on \u003csup\u003e18\u003c/sup\u003eFDGPET/CT were sclerotic.This observation may be relevant, especially in diseases such as breast and prostate cancer that progress with sclerotic bone metastases. Previous studies have highlighted the high diagnostic value of \u003csup\u003e18\u003c/sup\u003eFDG PET/CT in detecting bone metastases, while MRI exhibits high specificity but low sensitivity for this purpose(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). In our study, \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT detected more bone lesions and had a higher SUVmax than \u003csup\u003e18\u003c/sup\u003eFDG PET/CT in the cranium, vertebra, thorax, pelvis, and extremities. Significant differences were observed between the two modalities in terms of the SUVmax values of vertebral and thoracic lesions (p = 0.011 and p = 0.018, respectively).\u003c/p\u003e\u003cp\u003eMoreover, we analyzed the parameters that could possibly affect survival. The disease subtype of the patients in the cohort was a parameter affecting the OS. As it is known in database studies, OS times of stage-4 breast and lung cancers are significantly different(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). High levels of ALP and LDH in biochemical tests affected OS. Since ALP and LDH levels were in similar groups, ALP was included in the Cox-regression model(p \u0026lt; 0.001 and P = 0.004, respectively). In our study, the OS of patients with recurrent metastasis was significantly longer than that of patients with de novo metastasis. This may be because in our cohort some patients were diagnosed at an early stage and received curative treatment. Additionally, in cancers such as lung and pancreatic, the survival of patients with recurrent metastasisis longer than that of de novo patients(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). In our study, another important factor affecting OS was \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax of bone lesions. An important finding was that the \u003csup\u003e18\u003c/sup\u003eFDG PET/CT SUVmax value of bone lesions was not a factor affecting OS in the same patient cohort. In previous studies, the prognostic significance of the \u003csup\u003e18\u003c/sup\u003eFDGPET/CT SUVmax value in patients with bone metastases due to breast cancer was not observed(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). In our multivariate analysis performed for OS, we observed that the \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax value of bone lesions was a parameter as important as the cancer subtype.\u003c/p\u003e\u003cp\u003eOur study has some limitations:(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) its retrospective design and the relatively limited number of patients, including both de novo and with recurrence, and different cancer diagnoses;(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)the histopathology of the bone lesions was not confirmed due to the absence of bone biopsy;and (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) we did not perform a detailed lesion analysis, and only reported or mentioned lesions were analyzed. Nevertheless, our study is one of the few on this subject and reveals the prognostic importance of the \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax value. Moreover, the bone lesions included were those observed on both \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT and \u003csup\u003e18\u003c/sup\u003eFDGPET/CT and were most likely bone metastases.\u003c/p\u003e\u003cp\u003eIn conclusion, in patients with bone lesions due to various cancers, \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT detects more lesions and at higher SUVmax values than \u003csup\u003e18\u003c/sup\u003eFDGPET/CT. \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT additionally detects sclerotic bone lesions that are not usually detected in \u003csup\u003e18\u003c/sup\u003eFDGPET/CT. As the \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax value of the bone lesions increased, the overall survival time of the patients decreased. The prognostic value of \u003csup\u003e18\u003c/sup\u003eFDGPET/CT SUVmax value of bone lesions was not observed in the same patient group. The results of our study need to be confirmed in a more homogeneous patient group with lesions with histological confirmation and in studies involving more patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis research received no external funding.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConflict of interests:\u003c/strong\u003e \u003cp\u003eThe authors have no conflict of interests to declare regarding the publication of this paper.\u003c/p\u003e \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eColeman RE, Croucher PI, Padhani AR, et al. Bone metastases. Nat Rev Dis Primers. 2020;6:83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMichael HY, Hoffe SSE, Abrahm J, Pollock RE, Kheterpal A. Epidemiology, clinical presentation, and diagnosis of bone metastasis in adults. 2019.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFitzgerald AA, Weiner LM. The role of fibroblast activation protein in health and malignancy. Cancer Metastasis Rev. 2020;39:783\u0026ndash;803.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDong Y, Zhou H, Alhaskawi A et al. The Superiority of Fibroblast Activation Protein Inhibitor (FAPI) PET/CT Versus FDG PET/CT in the Diagnosis of Various Malignancies. Cancers (Basel) 2023;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuglielmo P, Alongi P, Baratto L et al. Head-to-Head Comparison of FDG and Radiolabeled FAPI PET: A Systematic Review of the Literature. Life (Basel) 2023;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEshet Y, Tau N, Apter S, et al. The Role of 68 Ga-FAPI PET/CT in Detection of Metastatic Lobular Breast Cancer. Clin Nucl Med. 2023;48:228\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eK\u0026ouml;mek H, Can C, Kaplan İ, et al. Comparison of [(68) Ga]Ga-DOTA-FAPI-04 PET/CT and [(18)F]FDG PET/CT in colorectal cancer. Eur J Nucl Med Mol Imaging. 2022;49:3898\u0026ndash;909.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen H, Pang Y, Li J, et al. Comparison of [(68)Ga]Ga-FAPI and [(18)F]FDG uptake in patients with gastric signet-ring-cell carcinoma: a multicenter retrospective study. Eur Radiol. 2023;33:1329\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu J, Wang Y, Liao T, et al. Comparison of the Relative Diagnostic Performance of [(68)Ga]Ga-DOTA-FAPI-04 and [(18)F]FDG PET/CT for the Detection of Bone Metastasis in Patients With Different Cancers. Front Oncol. 2021;11:737827.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi L, Hu X, Ma J, Yang S, Gong W, Zhang C. A systematic review of [(68)Ga]Ga-DOTA-FAPI-04 and [(18)F]FDG PET/CT in the diagnostic value of malignant tumor bone metastasis. Front Oncol. 2022;12:978506.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eŞahin E, Elboğa U, \u0026Ccedil;elen YZ, Sever \u0026Ouml;N, \u0026Ccedil;ayırlı YB, \u0026Ccedil;imen U. Comparison of (68)Ga-DOTA-FAPI and (18)FDG PET/CT imaging modalities in the detection of liver metastases in patients with gastrointestinal system cancer. Eur J Radiol. 2021;142:109867.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoodman GD. Mechanisms of Bone Metastasis. N Engl J Med. 2004;350:1655\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDondi F, Albano D, Treglia G, Bertagna F. Emerging Role of FAPI PET Imaging for the Assessment of Benign Bone and Joint Diseases. J Clin Med 2022;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGiesen N, Sprute R, R\u0026uuml;thrich M, et al. Evidence-based management of COVID-19 in cancer patients: Guideline by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO). Eur J Cancer. 2020;140:86\u0026ndash;104.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJi F, Fu SJ, Guo ZY, et al. Prognostic value of combined preoperative lactate dehydrogenase and alkaline phosphatase levels in patients with resectable pancreatic ductal adenocarcinoma. Med (Baltim). 2016;95:e4065.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQu X, Huang X, Yan W, Wu L, Dai K. A meta-analysis of \u0026sup1;⁸FDG-PET-CT, \u0026sup1;⁸FDG-PET, MRI and bone scintigraphy for diagnosis of bone metastases in patients with lung cancer. Eur J Radiol. 2012;81:1007\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGross-Erne M, Zimmerli L, Bassetti S, Li Q, Feller A, Mingrone W. A long-term retrospective observational study at a medium-sized medical oncology service in Switzerland: comparison of overall survival with a national cohort and adherence to treatment guidelines. Swiss Med Wkly. 2023;153:40091.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoore S, Leung B, Wu J, Ho C. Survival Implications of De Novo Versus Recurrent Metastatic Non\u0026ndash;Small Cell Lung Cancer. Am J Clin Oncol. 2019;42:292\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiotke L, Nevala-Plagemann C, Ying J, Florou V, Haaland B, Garrido-Laguna I. Treatment outcomes in recurrent versus de novo metastatic pancreatic adenocarcinoma: a real world study. BMC Cancer. 2022;22:1054.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeterson LM, O'Sullivan J, Wu QV, et al. Prospective Study of Serial (18)F-FDG PET and (18)F-Fluoride PET to Predict Time to Skeletal-Related Events, Time to Progression, and Survival in Patients with Bone-Dominant Metastatic Breast Cancer. J Nucl Med. 2018;59:1823\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable-1\u003c/strong\u003e:Baseline characteristics of the patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.43768996960486%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.56231003039514%\" valign=\"top\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.43768996960486%\" valign=\"top\"\u003e\n \u003cp\u003eAge, median, (range), years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.56231003039514%\" valign=\"top\"\u003e\n \u003cp\u003e55 (30\u0026ndash;83)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.43768996960486%\" valign=\"top\"\u003e\n \u003cp\u003eGender, n(%)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eFemale\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.56231003039514%\" valign=\"top\"\u003e\n \u003cp\u003e46(61,3)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e29(38,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.43768996960486%\" valign=\"top\"\u003e\n \u003cp\u003eLesion character, n(%)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eLytic\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eSclerotic\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eMixed.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.56231003039514%\" valign=\"top\"\u003e\n \u003cp\u003e42(30,2)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e81(58,3)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e16(11,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.43768996960486%\" valign=\"top\"\u003e\n \u003cp\u003eLocalization of bone Metastasis, n(%)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eCranium\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eVertebra\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eUpper limb\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eThorax\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003ePelvis\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eLower limb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.56231003039514%\" valign=\"top\"\u003e\n \u003cp\u003e7(5)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e41(29,5)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e3(2,2)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e31(22,3)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e43(30,9)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e14(10,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.43768996960486%\" valign=\"top\"\u003e\n \u003cp\u003eInspection purpose, n(%).\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eNewly diagnosed\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eSuspected recurrence or progression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.56231003039514%\" valign=\"top\"\u003e\n \u003cp\u003e48(64)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e27(36)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.43768996960486%\" valign=\"top\"\u003e\n \u003cp\u003eDisease type, n(%).\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eBreast cancer\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eLung cancer\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eGastrointestinal cancers\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eUrogenital cancers\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eThyroid cancer\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003eOther cancers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.56231003039514%\" valign=\"top\"\u003e\n \u003cp\u003e33(44)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e12(16)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e10(13,3)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e6(8)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e4(5,3)\u003c/p\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cp\u003e10(13,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable-2\u003c/strong\u003e: Univariable and multivariable analysis of factors affecting overall survival\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.827361563517915%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.34201954397394%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.83061889250814%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.55377574370709%\" valign=\"top\"\u003e\n \u003cp\u003eHR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.102974828375286%\" valign=\"top\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.494279176201374%\" valign=\"top\"\u003e\n \u003cp\u003eHR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.848970251716246%\" valign=\"top\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.827361563517915%\" valign=\"top\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.592833876221498%\" valign=\"top\"\u003e\n \u003cp\u003e0.380(0.252\u0026ndash;0.574)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.127035830618894%\" valign=\"top\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/td\u003e\n \u003ctd width=\"12.703583061889251%\" valign=\"top\"\u003e\n \u003cp\u003e0.437\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.827361563517915%\" valign=\"top\"\u003e\n \u003cp\u003eBone lesion FDG-PET SUVmax\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.592833876221498%\" valign=\"top\"\u003e\n \u003cp\u003e1.06(0.99\u0026ndash;1.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.127035830618894%\" valign=\"top\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/td\u003e\n \u003ctd width=\"12.703583061889251%\" valign=\"top\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.827361563517915%\" valign=\"top\"\u003e\n \u003cp\u003eBone lesion FAPI-PET SUVmax\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.592833876221498%\" valign=\"top\"\u003e\n \u003cp\u003e1.047(1.021\u0026ndash;1.075)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.127035830618894%\" valign=\"top\"\u003e\n \u003cp\u003e1.03(1.01\u0026ndash;1.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.703583061889251%\" valign=\"top\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.827361563517915%\" valign=\"top\"\u003e\n \u003cp\u003eDisease presentation (recurrence versus de novo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.592833876221498%\" valign=\"top\"\u003e\n \u003cp\u003e3.29(2.11\u0026ndash;5.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.127035830618894%\" valign=\"top\"\u003e\n \u003cp\u003e2.56(1.50\u0026ndash;4.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.703583061889251%\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.827361563517915%\" valign=\"top\"\u003e\n \u003cp\u003eLesion type (lytic versus sclerotic)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.592833876221498%\" valign=\"top\"\u003e\n \u003cp\u003e2.10(0.99\u0026ndash;4.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.127035830618894%\" valign=\"top\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/td\u003e\n \u003ctd width=\"12.703583061889251%\" valign=\"top\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.827361563517915%\" valign=\"top\"\u003e\n \u003cp\u003eDisease subtype (breast versus lung cancer)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.592833876221498%\" valign=\"top\"\u003e\n \u003cp\u003e0.95(0.48\u0026ndash;1.88)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.127035830618894%\" valign=\"top\"\u003e\n \u003cp\u003e0.74(0.27\u0026ndash;2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.703583061889251%\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.827361563517915%\" valign=\"top\"\u003e\n \u003cp\u003eAlkaline phosphatase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.592833876221498%\" valign=\"top\"\u003e\n \u003cp\u003e1.004(1.002\u0026ndash;1.005)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.127035830618894%\" valign=\"top\"\u003e\n \u003cp\u003e1.004(1.002\u0026ndash;1.006)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.703583061889251%\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"annals-of-nuclear-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anme","sideBox":"Learn more about [Annals of Nuclear Medicine](http://link.springer.com/journal/12149)","snPcode":"12149","submissionUrl":"https://www.editorialmanager.com/anme/default2.aspx","title":"Annals of Nuclear Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"68Ga-FAPI PET/CT, SUVmax, prognosis, bone metastasis","lastPublishedDoi":"10.21203/rs.3.rs-3973887/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3973887/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003eThis study aimed to compare and\u003csup\u003e18\u003c/sup\u003eFDGPET/CT in patients who develop bone metastases due to various cancers and to investigate the prognostic significance of the \u003csup\u003e68\u003c/sup\u003eFAPI-PET/CT SUVmax value for survival.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003ePatients with bone metastases who underwent both \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CTand\u003csup\u003e18\u003c/sup\u003eFDGPET/CT within a 1-week period were included in this retrospective study. The effect of the SUVmax value of bone lesions on overall survival was analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eA total of 75 eligible patients with 139 bone lesions were included in this study. The median age of the patients was 55(30–83) and 48 patients (64%) were newly diagnosed. The primary lesion median \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax value was higher than the median \u003csup\u003e18\u003c/sup\u003eFDGPET/CT SUVmax (10.75 versus 6.7). Bone lesions \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax median(IQR) were 7.8(4.6–13.2), and \u003csup\u003e18\u003c/sup\u003eFDGPET/CT SUVmax of bone lesions were 5.9(3.8–8.2). More bone lesions were detected on \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT than on \u003csup\u003e18\u003c/sup\u003eFDGPET/CT(median IQR 4 [1–9] versus 2 [1–6](p=0.014). The extra lesions observed on \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT were mostly sclerotic bone lesions(p = 0.001).\u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax was significantly higher in vertebra and thorax lesions(p=0.011 and p=0.018, respectively). While the bone lesion \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax affected the OS, the \u003csup\u003e18\u003c/sup\u003eFDGPET/CT SUVmax value did not affect the OS (p\u0026lt;0.001 and p=0.079, respectively). In ROC analysis, a cut-off value of \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax \u0026gt;7.7 was found for OS(AUC:0.619). The median OS in the group above the cut-off value was worse than that in the group below the cut-off value (32 versus 45) months (p=0.002). In the multivariate analysis for OS, the \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT SUVmax of bone lesions was an important parameter,as well as cancer subtype, ALP level, and disease occurrence.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT detected more bone lesions and higher SUVmax values than \u003csup\u003e18\u003c/sup\u003eFDGPET/CT in various cancers. The prognostic value of the SUVmax value of \u003csup\u003e68\u003c/sup\u003eGa-FAPI PET/CT bone lesions was observed regardless of disease subtype.\u003c/p\u003e","manuscriptTitle":"Prognostic significance of 68Ga-FAPI-PET/CT in patients with bone metastases in various cancers","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-23 18:58:49","doi":"10.21203/rs.3.rs-3973887/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-02-29T01:18:35+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-02-21T01:59:56+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-02-20T04:05:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Nuclear Medicine","date":"2024-02-19T15:48:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-nuclear-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anme","sideBox":"Learn more about [Annals of Nuclear Medicine](http://link.springer.com/journal/12149)","snPcode":"12149","submissionUrl":"https://www.editorialmanager.com/anme/default2.aspx","title":"Annals of Nuclear Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"7c6d0f73-6e88-43e8-85c5-9c4b02f999c0","owner":[],"postedDate":"February 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-05-07T20:08:07+00:00","versionOfRecord":{"articleIdentity":"rs-3973887","link":"https://doi.org/10.1007/s12149-024-01935-3","journal":{"identity":"annals-of-nuclear-medicine","isVorOnly":false,"title":"Annals of Nuclear Medicine"},"publishedOn":"2024-04-30 19:57:41","publishedOnDateReadable":"April 30th, 2024"},"versionCreatedAt":"2024-02-23 18:58:49","video":"","vorDoi":"10.1007/s12149-024-01935-3","vorDoiUrl":"https://doi.org/10.1007/s12149-024-01935-3","workflowStages":[]},"version":"v1","identity":"rs-3973887","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3973887","identity":"rs-3973887","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}