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Extensive research has been conducted on radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) and p-Cl-Phe-cyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH 2 (LM3) peptides for imaging of FAP and somatostatin receptor 2 (SSTR2)-positive tumors. In this study, we designed and synthesized a FAPI-LM3 heterobivalent molecule radiolabeled with 68 Ga and evaluated its effectiveness in both tumor xenografts and patients with nasopharyngeal carcinoma (NPC). Methods: The synthesis of FAPI-LM3 was based on the structures of FAPI-46 and LM3. After radiolabeling with 68 Ga, its dual-receptor-binding affinity was evaluated in vitro and in vivo. Preclinical studies, including small-animal PET and biodistribution evaluation, were conducted on HT-1080-FAP and HT-1080-SSTR2 tumor xenografts. The feasibility of 68 Ga-FAPI-LM3 PET/CT in a clinical setting was evaluated in patients with NPC, and the results were compared with those of 18 F-FDG. Results: 68 Ga-FAPI-LM3 showed high affinity for both FAP and SSTR2. The tumor uptake of 68 Ga-FAPI-LM3 was significantly higher than that of 68 Ga-FAPI-46 and 68 Ga-DOTA-LM3 in HT-1080-FAP-plus-HT-1080-SSTR2 tumor xenografts. In a clinical study involving 6 NPC patients, 68 Ga-FAPI-LM3 PET/CT showed significantly higher uptake than did 18 F-FDG in primary and metastatic lesions, leading to enhanced lesion detectability and tumor delineation. Conclusion: 68 Ga-FAPI-LM3 exhibited FAPI and SSTR2 dual-receptor-targeting properties both in vitro and in vivo, resulting in improved tumor uptake and retention compared with that observed with monomeric 68 Ga-FAPI and 68 Ga-DOTA-LM3. This study highlights the clinical feasibility of 68 Ga-FAPI-LM3 PET/CT for NPC imaging., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Abstract: SMARCA4-deficient undifferentiated carcinoma is a new clinical entity characterized by SMARCA4 inactivation and has a dismal prognosis because of rapid growth. In this case, we reported 18 F-FDG and 68 Ga-FAPI-46 PET/CT imaging findings in a patient with SMARCA4-deficient undifferentiated carcinoma of stomach. 68 Ga-FAPI-46 PET/CT showed much higher tumor-to-background contrast of primary tumor and revealed more metastatic lesions than 18 F-FDG PET/CT. This case demonstrated the superiority of 68 Ga-FAPI PET/CT over 18 F-FDG for identifying both primary and metastatic lesions in SMARCA4-deficient undifferentiated carcinoma. This observation may add the information on the benefit of FAPI PET in oncology imaging., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Radiolabeled fibroblast activation protein inhibitor (FAPI) has been introduced as a promising PET tracer for imaging of pancreatic cancer. To date, FAPI PET/computed tomography (CT) has generally but not universally yielded higher radiotracer uptake and tumor-to-background contrast than 18 F-fluorodeoxyglucose PET/CT in primary tumors, involved lymph nodes, and visceral metastases. It may also be useful for the evaluation of the tumor response to chemotherapy. However, increased FAPI uptake may be observed in benign conditions, including pancreatitis, pancreatic tuberculosis, IgG4-related disease, and serous cystadenoma, and therefore, clinical, radiological, and pathological correlations are required., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Abstract: Epithelioid hemangioendothelioma (EHE) is a rare type of vascular tumor that may arise in bone. Here we presented a 62-year-old man with suspected bone metastases who underwent PET/CT to detect the primary tumor. He underwent 18 F-FDG and 68 Ga-FAPI PET/CT under the prospective trial NCT04416165. Radiotracer uptake was much higher with 68 Ga-FAPI PET/CT than with 18 F-FDG PET/CT in most of bone lesions. No intense uptake likely presenting the primary tumor was observed. Subsequent bone biopsy confirmed the diagnosis of EHE of bone. This case suggested that 68 Ga-FAPI PET/CT might be a useful tool for evaluation of EHE., Competing Interests: Conflicts of interest and sources of funding: The authors have no conflicts of interest to report. This report was sponsored by the National Natural Science Foundation of China (grand number 82071961)., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: 68 Ga-labeled PET tracer targeting PSMA is a promising diagnostic approach for staging and restating of prostate cancer (PCa), but cases with clinically relevant PCa and false-negative PSMA PET/CT have been reported. In this case, we reported 68 Ga-PSMA, 18 F-FDG, and 68 Ga-FAPI PET/CT findings in a 65-year-old man with de novo metastatic PCa. 68 Ga-FAPI PET/CT detected non-PSMA/FDG-avid primary PCa, consisting with multiparametric MRI findings. The subsequent histopathologic examination confirmed a Gleason 4 + 5 PCa. This case highlighted that 68 Ga-FAPI PET/CT may be a useful imaging modality for primary PCa detection and localization., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Metastases to gastrointestinal tract from breast cancer are very rare and can be diagnostically challenging. In this case, we reported 18 F-FDG and 68 Ga-FAPI PET/CT findings in a 54-year-old women with such uncommon metastases from breast cancer. Although the primary tumor of breast cancer remained radiologically occult, 68 Ga-FAPI PET/CT showed a far better tumor-to-background ratio than 18 F-FDG PET/CT for detecting the metastatic lesions, especially for detecting the retroperitoneal lymph node and rectal metastases., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Cancer-associated fibroblasts (CAFs) are crucial components of the tumor microenvironment. Fibroblast activation protein (FAP) is overexpressed in CAFs. FAP-targeted molecular imaging agents, including the FAP inhibitors (FAPIs) 04 and 46, have shown promising results in tumor diagnosis. However, these molecules have a relatively short tumor-retention time for peptide-targeted radionuclide therapy applications. We aimed to design a 68 Ga-labeled FAPI dimer, 68 Ga-DOTA-2P(FAPI) 2 , to optimize the pharmacokinetics and evaluate whether this form is more effective than its monomeric analogs. Methods: 68 Ga-DOTA-2P(FAPI) 2 was synthesized on the basis of the quinoline-based FAPI variant (FAPI-46), and its binding properties were assayed in CAFs. Preclinical pharmacokinetics were determined in FAP-positive patient-derived xenografts using small-animal PET and biodistribution experiments. The effective dosimetry of 68 Ga-DOTA-2P(FAPI) 2 was evaluated in 3 healthy volunteers, and PET/CT imaging of 68 Ga-FAPI-46 and 68 Ga-DOTA-2P(FAPI) 2 was performed on 3 cancer patients. Results: 68 Ga-DOTA-2P(FAPI) 2 was stable in phosphate-buffered saline and fetal bovine serum for 4 h. The FAPI dimer showed high affinity and specificity for FAP in vitro and in vivo. The tumor uptake of 68 Ga-DOTA-2P(FAPI) 2 was approximately 2-fold stronger than that of 68 Ga-FAPI-46 in patient-derived xenografts, whereas healthy organs showed low tracer uptake and fast body clearance. The effective dose of 68 Ga-DOTA-2P(FAPI) 2 was 1.19E-02 mSv/MBq, calculated using OLINDA. Finally, the PET/CT scans of the 3 cancer patients revealed higher intratumoral uptake of 68 Ga-DOTA-2P(FAPI) 2 than of 68 Ga-FAPI-46 in all tumor lesions (SUV max , 8.1-39.0 vs. 1.7-24.0, respectively; P < 0.001). Conclusion: 68 Ga-DOTA-2P(FAPI) 2 has increased tumor uptake and retention properties compared with 68 Ga-FAPI-46, and it could be a promising tracer for both diagnostic imaging and targeted therapy of malignant tumors with positive expression of FAP., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Abstract: The prevalence of primary hepatic mucosa-associated lymphoid tissue lymphomas is extremely low. In this case, we present 18F-FDG and 68Ga-FAPI PET/CT findings in a 76-year-old man with pathologically confirmed primary hepatic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. 68Ga-FAPI PET/CT showed a better tumor-to-background ratio than 18F-FDG PET/CT in the hepatic lesion because there is little 68Ga-FAPI uptake in the liver parenchyma. This case indicates that 68Ga-FAPI PET/CT may be an alternate method for evaluating hepatic involvement of lymphoma, especially for the non-FDG-avid lymphomas., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Accurate clinical staging is crucial for managing nasopharyngeal carcinoma (NPC). However, false-positive finding of cervical lymph nodes in 18F-FDG PET/CT and MRI may lead to unnecessary chemotherapy for NPC. In this case, we report a patient with NPC who was incorrectly diagnosed with bilateral cervical lymph node metastases by both 18F-FDG PET/CT and MRI. Subsequent pathology results showed proliferating lymphoid cells with no signs of tumor metastasis. Interestingly, no abnormal 68Ga-FAPI uptake was observed in the nonmetastatic reactive lymph nodes. Therefore, 68Ga-FAPI PET/CT may be useful for assessment of pretreatment lymph node status in NPC., Competing Interests: Conflicts of interest and sources of funding: This report was funded by National Natural Science Foundation of China (grant number 82071961). The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study aimed to investigate the diagnostic performance of [ 68 Ga]Ga-FAPI PET/CT for primary and metastatic pancreatic carcinoma lesions and compare the results with those of [ 18 F]-fluorodeoxyglucose ([ 18 F]FDG) PET/CT., Methods: Patients with suspected or diagnosed pancreatic malignancy, who underwent contemporaneous [ 18 F]FDG and [ 68 Ga]Ga-FAPI PET/CT between June 2020 and January 2021, were retrospectively analyzed. Routine contrast-enhanced CT (CE-CT) is performed in all patients as standardized care. Findings were confirmed by histopathology or radiographic follow-up. We compared radiotracer uptake, diagnostic performance, and TNM (tumor-node-metastasis) classifications., Results: We evaluated 36 participants (25/36 men; median age, 60 years), including 26 patients with pancreatic malignancies and ten patients with pancreatic benign lesions. [ 68 Ga]Ga-FAPI PET/CT showed higher radiotracer uptake and higher sensitivity than [ 18 F]FDG PET/CT in evaluating primary tumors (SUVmax, 21.4 vs. 4.8; sensitivity, 100% vs. 73.1%), involved lymph nodes (SUVmax, 8.6 vs. 2.7; sensitivity, 81.8% vs. 59.1%), and metastases (SUVmax, 7.9 vs. 3.5; sensitivity, 91.5% vs. 44.0%); Compared with [ 18 F]FDG, [ 68 Ga]Ga-FAPI PET/CT upstaged six patients' TNM staging (6/23, 26.1%) and changed two patients' clinical management (2/23, 8.7%). Compared with CE-CT, [ 68 Ga]Ga-FAPI PET/CT upgraded TNM staging in five patients (5/23, 21.7%) and changed the therapeutic regimen in only one patient (1/23, 4.3%). Intense [ 68 Ga]Ga-FAPI uptake was observed throughout the pancreas in 12/26 pancreatic malignancies; dual-time point [ 68 Ga]Ga-FAPI PET/CT may differentiate pancreatitis from malignancy., Conclusions: Compared with [ 18 F]FDG PET/CT, [ 68 Ga]Ga-FAPI PET/CT shows higher sensitivity in detecting primary pancreatic tumors, involved lymph nodes, and metastases and is superior in terms of TNM staging. Prospective trials with larger patient population are needed to evaluate whether [ 68 Ga]Ga-FAPI PET/CT could elicit treatment modification in pancreatic cancer when compared with standard of care imaging., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: Pineal yolk sac tumors (YSTs) are a rare type of extragonadal YST. They make up a small fraction of all intracranial germ cell tumors and an even small fraction of pineal masses overall. This study reported a case of pineal YST with α-fetoprotein production revealed by 18F-FDG and 68Ga-FAPI PET/MRI. In the PET images, 68Ga-FAPI showed a far better tumor-to-background ratio than 18F-FDG in the pineal YST because there is little 68Ga-FAPI uptake in the brain. This case indicates that 68Ga-FAPI PET/MRI may be a useful tool for evaluating intracranial YST and other types of tumors in central nervous system., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: 18F-FDG PET/CT is a useful imaging modality for detecting disease recurrence and metastases in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). However, the sensitivity of 18F-FDG PET/CT in RAIR-DTC is not very satisfactory. 68Ga-FAPI is a promising PET tracer that allowed imaging of various types of cancer. In this case, 68Ga-FAPI showed a far better signal-to-background ratio than 18F-FDG for detecting the RAIR-DTC metastatic lesions, especially for detecting the small pulmonary metastases. Therefore, 68Ga-FAPI may be a promising alternative to 18F-FDG for detecting tumor recurrence and metastases in RAIR-DTC. It could also be used for guiding FAP-targeted radionuclide therapy., Competing Interests: Conflicts of interest and sources of funding: This report was sponsored by the medical and health guidance projects of Xiamen (3502Z20209269 and 3502Z20189010). None of the authors have any conflict of interest to declare., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study aimed to explore the clinical utility of [ 68 Ga]Ga-labeled fibroblast activation protein inhibitor ([ 68 Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) relative to [ 18 F]-fluorodeoxyglucose ([ 18 F]FDG) PET/CT and magnetic resonance imaging (MRI) for primary staging and recurrence detection in nasopharyngeal carcinoma (NPC)., Methods: This retrospective analysis utilized a sub-cohort of patients from a previously acquired database. Patients with NPC who underwent [ 18 F]FDG and [ 68 Ga]Ga-FAPI PET/CT between October 2019 and November 2020 were included. The radiotracer uptake and clinical staging/restaging performances of [ 18 F]FDG and [ 68 Ga]Ga-FAPI PET/CT were compared., Results: Forty-five participants (39 for initial assessment, 6 for recurrence detection) were included. In treatment-naïve participants, [ 68 Ga]Ga-FAPI PET/CT showed higher radiotracer uptake than [ 18 F]FDG PET/CT in primary tumors (16.18 vs. 10.11, P < 0.001), regional lymph nodes (11.42 vs. 7.37, P < 0.001), and bone and visceral metastases (6.94 vs. 3.11, P < 0.001). Compared with the [ 18 F]FDG-based TNM stage, the [ 68 Ga]Ga-FAPI-based TNM stage was upgraded in ten patients (26%), resulting in management changes in seven patients (18%). Compared with MRI, [ 68 Ga]Ga-FAPI PET/CT upgraded and underestimated the T stage in four and two patients, respectively. In post-treatment patients, [ 68 Ga]Ga-FAPI PET/CT yielded more true-positive findings than [ 18 F]FDG PET/CT in detecting local recurrence., Conclusion: [ 68 Ga]Ga-FAPI PET/CT is a promising imaging modality for the diagnosis of primary and metastatic NPC. The exact tumor geographic imaging obtained through [ 68 Ga]Ga-FAPI PET/CT may be a supplement to MRI for T staging and radiotherapy planning., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: A 55-year-old woman underwent 18F-FDG and 68Ga-FAPI PET/CT for tumor detection and staging under the prospective study NCT04416165. Both scans showed a mass lesion with increased tracer uptake in the pancreas. Moreover, 68Ga-FAPI PET/CT showed a greater number of abnormal foci in the mesentery and omentum than that shown with 18F-FDG. These abnormal foci were suspected to be metastases from pancreatic cancer. The patient subsequently underwent a cytoreductive surgery, and postoperative histopathology confirmed the diagnosis of acinar cell carcinoma of pancreas. Follow-up 68Ga-FAPI PET/CT (3 months after surgery) showed an excellent response with decreasing 68Ga-FAPI activity in the whole abdomen., Competing Interests: Conflicts of interest and sources of funding: none declare., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Purpose: To compare 68 Ga-fibroblast activation protein inhibitor (FAPI) and 18 F-FDG PET/CT in imaging locally advanced oesophageal cancer, and evaluate the potential usefulness of 68 Ga-FAPI PET/CT on gross target volume (GTV) delineation aimed at radiotherapy planning for oesophageal cancer as compared with contrast-enhanced CT (CE-CT) and 18 F-FDG PET/CT., Materials and Methods: Twenty-one patients with newly diagnosed oesophageal cancer who underwent both 18 F-FDG and 68 Ga-FAPI PET/CT scans were selected. GTVs of the primary tumours based on CE-CT (GTV CT ), PET/CT, and CE-CT plus PET/CT were delineated. Gross tumour lengths were measured by GTVs and endoscopy and recorded., Results: The 68 Ga-FAPI PET showed significantly higher radiotracer uptake than 18 F-FDG PET (median SUVmax 16.71 vs. 11.23; P = 0.002) in the primary tumours. SUV thresholds of FAPI ×20%, 30%, 40%, and FDG ×40% showed similar lesion lengths compared with that in endoscopic examination (P > 0.05). GTV CT demonstrated the largest volume (median: 48.80 mm 3 , range: 14.83-162.23 mm 3 ) than PET-based GTVs. For PET/CT-guided complementary contouring of GTV CT , four patients (19%) were increased by FAPI ×20% and 30%, two patients (9.5%) were increased by FAPI ×40%, and only one patient was increased by FDG ×40%. Furthermore, the volume of GTV based on CE-CT plus FAPI ×20%, 30%, and 40% showed no significant difference with GTV CT and planning target volume based CE-CT plus FAPI-PET and meets the organ at risk standard., Conclusion: The 68 Ga-FAPI PET/CT methodology showed favourable tumour-to-background contrast in oesophageal cancer and might provide additional information for target volume delineation and help avoid tumour geographic misses., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: This study aimed to evaluate the potential utility of [ 68 Ga]Ga-FAPI-04 PET/CT for diagnosing primary and metastatic lesions in patients with liver cancer, as well as to compare it with contrast-enhanced CT (CE-CT), liver MRI, and [ 18 F]-FDG PET/CT., Methods: We performed a single-center post hoc retrospective analysis of data obtained from a prospective parent study (NCT04416165). This study included 34 patients diagnosed with or suspected hepatic lesions who underwent concomitant [ 68 Ga]Ga-FAPI-04 and [ 18 F]-FDG/CT scans. Moreover, these patients underwent liver MRI (n = 34) and CE-CT (n = 25). Histopathologic (n = 62) or radiographic follow-up (n = 128) served as the reference standard for the final diagnosis., Results: Among the 34 patients, 20, 12, and 2 patients presented with hepatocellular carcinomas, intrahepatic cholangiocarcinomas, and benign hepatic nodules, respectively. The sensitivities of CE-CT, MRI, [ 68 Ga]Ga-FAPI-04, and [ 18 F]-FDG/CT for detecting primary liver tumors were 96%, 100%, 96%, and 65%, respectively. Regarding the diagnosis of all intrahepatic lesions, the per-lesion detection rate of [ 68 Ga]Ga-FAPI-04 PET/CT was slightly lower than that of MRI (85% vs. 100%, P = 0.34) and significantly higher than that of [ 18 F]-FDG PET/CT (85% vs. 52%, P < 0.001). Regarding the diagnosis of all malignant lesions (including extrahepatic disease), the tumor detection rate of [ 68 Ga]Ga-FAPI-04 PET/CT was 87.4%, which was significantly higher than that of [ 18 F]-FDG PET/CT (65.0%, P < 0.001)., Conclusions: Our findings indicate that the sensitivity of [ 68 Ga]Ga-FAPI-04 PET/CT to correctly identify primary liver tumors and metastatic lesions is equivalent to that of CE-CT and liver MRI. Moreover, [ 68 Ga]Ga-FAPI-04 PET/CT is better at identifying liver lesions than [ 18 F]-FDG PET/CT, and its use may improve tumor staging, recurrence detection, and implementation of necessary treatment modifications.

Abstract: A 50-year-old woman with a newly detected pulmonary ground-glass opacity (GGO) nodule underwent PET/CT to determine the likelihood of malignancy. This patient was enrolled in the prospective study (NCT04588064) to determine the effectiveness of 18F-FDG and 68Ga-FAPI PET/CT for characterization of the GGO nodule. On PET/CT images, minimal 18F-FDG uptake but intense 68Ga-FAPI uptake was observed in this GGO nodule. This patient subsequently underwent video-assisted thoracoscopic surgery, and postoperative pathological examination confirmed the diagnosis of invasive adenocarcinoma. This case presented an example where 68Ga-FAPI PET/CT showed higher tracer uptake than 18F-FDG in the malignant GGO nodule., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: A 56-year-old woman presented with edema in the upper part of the body, enlarged axillary lymph nodes, and progressive bone pain for 1 year. Malignant disease was initially suspected. This patient underwent 68Ga-DOTA-FAPI-04 PET/CT for detection of the primary lesion and evaluation of disease extent. 68Ga-DOTA-FAPI-04 PET/CT revealed multiple abnormal foci at the skeleton, muscle, lymph nodes, and subcutaneous fat. The imaging findings, highly suggestive of Erdheim-Chester disease, have been later confirmed by histopathology. This case highlights that 68Ga-DOTA-FAPI-04 PET/CT would be useful for evaluating the disease extent, guiding biopsies, and gauging the treatment response in patients with Erdheim-Chester disease., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background Accurate clinical staging is crucial to managing gastrointestinal cancer, but fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) PET/CT has limitations. Targeting fibroblast-activation protein is a newer diagnostic approach for the visualization of tumor stroma, and gallium 68 ( 68 Ga)-labeled fibroblast-activation protein inhibitors (FAPIs), hereafter 68 Ga-FAPIs, present a promising alternative to 18 F-FDG. Purpose To compare the diagnostic efficacy of 68 Ga-FAPI PET/CT in primary and metastatic lesions of gastrointestinal malignancies with that of 18 F-FDG PET/CT. Materials and Methods Images from patients with gastric, duodenal, and colorectal cancers who underwent contemporaneous 18 F-FDG and 68 Ga-FAPI PET/CT between October 2019 through June 2020 were retrospectively analyzed. 18 F-FDG and 68 Ga-FAPI uptakes were compared by using the Wilcoxon signed-rank test. The McNemar test was used to compare the diagnostic performance between the two techniques. Results Thirty-five patients (median age, 64 years [interquartile range, 53-68 years]; 18 men) were evaluated. In treatment-naive patients ( n = 19), 68 Ga-FAPI PET/CT led to upstaging of the clinical TNM stage in four (21%) patients compared with 18 F-FDG PET/CT. Tracer uptake was higher with 68 Ga-FAPI PET/CT than with 18 F-FDG PET/CT in primary lesions (gastric cancer: 12.7 vs 3.7, respectively, P = .003; colorectal cancer: 15.9 vs 7.9, P = .03), involved lymph nodes (6.7 vs 2.4, P < .001), and bone and visceral metastases (liver metastases: 9.7 vs 5.2, P < .001; peritoneal metastases: 8.4 vs 3.6, P < .001; bone metastases: 4.3 vs 2.2, P < .001; lung metastases: 4.4 vs 1.9, P = .01). In addition, the sensitivity of 68 Ga-FAPI PET/CT was higher than that of 18 F-FDG PET/CT in the detection of primary tumors (100% [19 of 19] vs 53% [10 of 19], respectively; P = .004), lymph nodes (79% [22 of 28] vs 54% [15 of 28], P < .001), and bone and visceral metastases (89% [31 of 35] vs 57% [20 of 35], P < .001). Conclusion Gallium 68 fibroblast-activation protein inhibitor PET/CT was superior to fluorine 18 fluorodeoxyglucose PET/CT in the detection of primary and metastatic lesions in gastric, duodenal, and colorectal cancers, with higher tracer uptake in most primary and metastatic lesions. Published under a CC BY 4.0 license.

Abstract: 18F-FDG PET/CT was performed to locate the primary lesion in a 71-year-old man with bone metastasis. However, no abnormal 18F-FDG activity likely presenting the primary tumor was observed. 68Ga-fibroblast activation protein inhibitor PET/CT was then performed for further detecting the primary tumor, which showed a higher activity in lesions of bone metastases than 18F-FDG. Additionally, another lesion with intense uptake was observed in the inferior pole of right kidney, likely presenting the primary tumor. A renal biopsy revealed the diagnosis of chromophobe renal cell carcinoma. This case highlighted that 68Ga-fibroblast activation protein inhibitor could be a promising radiopharmaceutical in the diagnosis of renal cell carcinoma., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This prospective study aimed to evaluate the potential usefulness of [ 68 Ga]Ga-DOTA-FAPI-04 positron emission tomography/computed tomography (PET/CT) in the oncological evaluation of patients presenting with inconclusive [ 18 F]FDG PET/CT findings., Methods: [ 68 Ga]Ga-DOTA-FAPI-04 was performed in patients presenting with inconclusive [ 18 F]FDG PET/CT findings. Tumour uptake was quantified by the maximum standard uptake value (SUV). Histopathology or follow-up imaging served as the standard for the final diagnosis., Results: A total of 68 patients with inconclusive [ 18 F]FDG PET/CT findings underwent additional [ 68 Ga]Ga-DOTA-FAPI-04 PET/CT. Of them, 18 (26.5%) were for discrimination of mass lesions detected on conventional imaging, 6 (8.8%) for detection of the unknown primary site in biopsy-proven metastatic malignancy, 21 (30.9%) for the staging of cancer, and the other 23 (33.8%) for evaluation of suspected disease recurrence. Most of the primary and metastatic lesions demonstrated higher uptake of [ 68 Ga]Ga-DOTA-FAPI-04 than did [ 18 F]FDG, which resulted in favourable tumour-to-background contrast in various types of cancer. As a result, [ 68 Ga]Ga-DOTA-FAPI-04 PET/CT identified suspicious mass lesions with an accuracy of 12/18 (66.7%), detected the primary site in 4/6 patients (66.7%) with unknown malignancy, upgraded tumour staging in 7/21 patients (33.3%), and detected disease recurrence in 20/23 patients (87.0%)., Conclusions: In patients undergoing oncological evaluation with inconclusive [ 18 F]FDG PET/CT findings, [ 68 Ga]Ga-DOTA-FAPI-04 may have a complementary role in discriminating mass lesions on conventional imaging, locating the primary site of unknown malignancy, modifying tumour staging, and detecting suspected disease recurrence. Nevertheless, careful attention should be paid when reading the [ 68 Ga]Ga-DOTA-FAPI-04 PET/CT images in tumours complicated with inflammation.

A 60-year-old woman, previously treated for breast cancer, was referred to gastroenterologists due to persistent abdominal distension. F-FDG PET/CT revealed multiple abnormal foci at the skeleton including the bilateral ilium, peritoneum, and omentum. Ga-FAPI PET/CT was performed for further detecting the primary lesion, which showed a greater number of bone metastases and higher uptake in peritoneal carcinomatoses than F-FDG. Biopsy at the left ilium and omentum indicated metastases from breast cancer. This case highlighted that Ga-FAPI may outperforms F-FDG PET/CT in identifying bone metastasis and peritoneal carcinomatosis.

We presented a case of 64-year-old woman with pathologically diagnosed lung adenocarcinoma. Brain metastases were highly suspected due to the appearance of neurological symptoms. However, no abnormal finding in the brain was observed on F-FDG PET/CT. Contrast-enhanced MRI showed the presence of leptomeningeal metastases but with a negative cerebrospinal fluid analysis. For this reason, the patient underwent Ga-FAPI PET/CT, later fused with MRI scans that showed intense uptake of Ga-FAPI in leptomeningeal regions correspondent to the sites of gadolinium enhancement. This case highlights that Ga-FAPI would be promising for the identification of leptomeningeal involvement in patients with malignant disease.

A 75-year-old man with a history of prostate cancer (T1N0M0, Gleason score 4 + 3) was referred to radionuclide bone scan and Ga-PSMA PET/CT to detect recurrence. Multiple abnormal foci were observed in the axial and appendicular skeleton, which were suggestive of metastatic superscan from prostate cancer. However, histopathological examinations (from bone biopsy) did not support the metastases from prostate cancer. Ga-FAPI PET/CT was then performed to detect the occult tumor, which showed intense activity in the gastric wall. Subsequent gastroscopy examination revealed the diagnosis of GSRCC (gastric signet-ring cell carcinoma). The diagnosis of GSRCC with widespread bone metastases was finally made.

The present study compared Ga-FAPI and F-FDG PET/CT in a patient with cholangiocellular carcinoma. In this case, Ga-FAPI PET shows much higher tumor-to-background contrast of primary tumor and reveals more metastatic lesions, especially the micrometastases of bones, than F-FDG PET.

Purpose: We evaluated the potential usefulness of [ 68 Ga]Ga-DOTA-FAPI-04 positron emission tomography/computed tomography (PET/CT) for the diagnosis of primary and metastatic lesions in various types of cancer, compared with [ 18 F] FDG PET/CT., Methods: A total of 75 patients with various types of cancer underwent contemporaneous [ 68 Ga]Ga-DOTA-FAPI-04 and [ 18 F] FDG PET/CT either for an initial assessment or for recurrence detection. Tumour uptake was quantified by the maximum standard uptake value (SUV max ). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of [ 18 F] FDG and [ 68 Ga]Ga-DOTA-FAPI-04 PET/CT were calculated and compared to evaluate the diagnostic efficacy., Results: The study cohort consisted of 75 patients (47 males and 28 females; median age, 61.5 years; age range, 32-85 years). Fifty-four patients with 12 different tumour entities underwent paired [ 68 Ga]Ga-DOTA-FAPI-04 and [ 18 F] FDG PET/CT for initial assessment, while the other 21 patients underwent paired scans for recurrence detection. [ 68 Ga]Ga-DOTA-FAPI-04 PET/CT was able to clearly identify 12 types of malignant tumours with favourable tumour-to-background contrast, which resulted in a higher detection rate of primary tumours than did [ 18 F] FDG PET/CT (98.2% vs. 82.1%, P = 0.021). Meanwhile, [ 68 Ga]Ga-DOTA-FAPI-04 PET/CT showed a better sensitivity than [ 18 F] FDG PET/CT in the detection of lymph nodes (86.4% vs. 45.5%, P = 0.004) and bone and visceral metastases (83.8% vs. 59.5%, P = 0.004)., Conclusion: [ 68 Ga]Ga-DOTA-FAPI-04 PET/CT showed a superior diagnostic efficacy than [ 18 F] FDG PET/CT for the diagnosis of primary and metastatic lesions in patients with various types of cancer, especially in identifying liver metastases, peritoneal carcinomatosis, and brain tumours.

Purpose: The aim of this study was to explore the role of [68Ga]Ga-DOTA-FAPI-04 positron emission tomography/computed tomography (PET/CT), compared with 18F-fluorodeoxyglucose [18F]-FDG PET/CT, for evaluating peritoneal carcinomatosis in patients with various types of cancer. Methods: Patients with suspected peritoneal malignancy, who underwent both [18F]-FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT between October 2019 and August 2020, were retrospectively analysed. The radiotracer uptake, peritoneal cancer index (PCI) score, and diagnostic performance of [18F]-FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT were evaluated and compared. Results: Our cohort consisted of 46 patients, including 16 patients with diffuse-type peritoneal carcinomatosis, 27 with nodular-type peritoneal carcinomatosis, and 3 true-negative patients. A significant difference in standard uptake values (SUV) of lesions between [18F]-FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT examination was observed (median SUV: 3.48 vs. 9.82; P < 0.001), particularly in peritoneal carcinomatosis from gastric cancer (median SUV: 3.44 vs. 8.05; P = 0.001). Moreover, [68Ga]Ga-DOTA-FAPI-04 PET/CT showed a higher PCI score and better sensitivity than [18F]-FDG PET/CT for the detection of peritoneal carcinomatosis (6 vs. 18; P < 0.001; 72.09% vs. 97.67%; P = 0.002). Conclusion: [68Ga]Ga-DOTA-FAPI-04 PET/CT demonstrated superior sensitivity over [18F]-FDG PET/CT for the detection of peritoneal carcinomatosis in patients with various types of cancer, particularly gastric cancer. Furthermore, the uptake of [68Ga]Ga-DOTA-FAPI-04 in peritoneal carcinomatosis was significantly higher than that of [18F]-FDG, demonstrating a larger extent of the lesions and yielding a higher PCI score. This could help enhance the image contrast, improve physicians' diagnostic confidence, and reduce the proportion of missed diagnoses. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the potential utility of [68Ga]Ga-FAPI-04 PET/CT for diagnosing primary and metastatic lesions in patients with liver cancer, as well as to compare it with contrast-enhanced CT (CE-CT), liver MRI, and [18F]-FDG PET/CT. Methods: We performed a single-center post hoc retrospective analysis of data obtained from a prospective parent study (NCT04416165). This study included 34 patients diagnosed with or suspected hepatic lesions who underwent concomitant [68Ga]Ga-FAPI-04 and [18F]-FDG/CT scans. Moreover, these patients underwent liver MRI (n = 34) and CE-CT (n = 25). Histopathologic (n = 62) or radiographic follow-up (n = 128) served as the reference standard for the final diagnosis. Results: Among the 34 patients, 20, 12, and 2 patients presented with hepatocellular carcinomas, intrahepatic cholangiocarcinomas, and benign hepatic nodules, respectively. The sensitivities of CE-CT, MRI, [68Ga]Ga-FAPI-04, and [18F]-FDG/CT for detecting primary liver tumors were 96%, 100%, 96%, and 65%, respectively. Regarding the diagnosis of all intrahepatic lesions, the per-lesion detection rate of [68Ga]Ga-FAPI-04 PET/CT was slightly lower than that of MRI (85% vs. 100%, P = 0.34) and significantly higher than that of [18F]-FDG PET/CT (85% vs. 52%, P < 0.001). Regarding the diagnosis of all malignant lesions (including extrahepatic disease), the tumor detection rate of [68Ga]Ga-FAPI-04 PET/CT was 87.4%, which was significantly higher than that of [18F]-FDG PET/CT (65.0%, P < 0.001). Conclusions: Our findings indicate that the sensitivity of [68Ga]Ga-FAPI-04 PET/CT to correctly identify primary liver tumors and metastatic lesions is equivalent to that of CE-CT and liver MRI. Moreover, [68Ga]Ga-FAPI-04 PET/CT is better at identifying liver lesions than [18F]-FDG PET/CT, and its use may improve tumor staging, recurrence detection, and implementation of necessary treatment modifications. [ABSTRACT FROM AUTHOR]

Purpose: This prospective study aimed to evaluate the potential usefulness of [68Ga]Ga-DOTA-FAPI-04 positron emission tomography/computed tomography (PET/CT) in the oncological evaluation of patients presenting with inconclusive [18F]FDG PET/CT findings. Methods: [68Ga]Ga-DOTA-FAPI-04 was performed in patients presenting with inconclusive [18F]FDG PET/CT findings. Tumour uptake was quantified by the maximum standard uptake value (SUV). Histopathology or follow-up imaging served as the standard for the final diagnosis. Results: A total of 68 patients with inconclusive [18F]FDG PET/CT findings underwent additional [68Ga]Ga-DOTA-FAPI-04 PET/CT. Of them, 18 (26.5%) were for discrimination of mass lesions detected on conventional imaging, 6 (8.8%) for detection of the unknown primary site in biopsy-proven metastatic malignancy, 21 (30.9%) for the staging of cancer, and the other 23 (33.8%) for evaluation of suspected disease recurrence. Most of the primary and metastatic lesions demonstrated higher uptake of [68Ga]Ga-DOTA-FAPI-04 than did [18F]FDG, which resulted in favourable tumour-to-background contrast in various types of cancer. As a result, [68Ga]Ga-DOTA-FAPI-04 PET/CT identified suspicious mass lesions with an accuracy of 12/18 (66.7%), detected the primary site in 4/6 patients (66.7%) with unknown malignancy, upgraded tumour staging in 7/21 patients (33.3%), and detected disease recurrence in 20/23 patients (87.0%). Conclusions: In patients undergoing oncological evaluation with inconclusive [18F]FDG PET/CT findings, [68Ga]Ga-DOTA-FAPI-04 may have a complementary role in discriminating mass lesions on conventional imaging, locating the primary site of unknown malignancy, modifying tumour staging, and detecting suspected disease recurrence. Nevertheless, careful attention should be paid when reading the [68Ga]Ga-DOTA-FAPI-04 PET/CT images in tumours complicated with inflammation. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the potential usefulness of [68Ga]Ga-DOTA-FAPI-04 positron emission tomography/computed tomography (PET/CT) for the diagnosis of primary and metastatic lesions in various types of cancer, compared with [18F] FDG PET/CT. Methods: A total of 75 patients with various types of cancer underwent contemporaneous [68Ga]Ga-DOTA-FAPI-04 and [18F] FDG PET/CT either for an initial assessment or for recurrence detection. Tumour uptake was quantified by the maximum standard uptake value (SUVmax). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of [18F] FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT were calculated and compared to evaluate the diagnostic efficacy. Results: The study cohort consisted of 75 patients (47 males and 28 females; median age, 61.5 years; age range, 32–85 years). Fifty-four patients with 12 different tumour entities underwent paired [68Ga]Ga-DOTA-FAPI-04 and [18F] FDG PET/CT for initial assessment, while the other 21 patients underwent paired scans for recurrence detection. [68Ga]Ga-DOTA-FAPI-04 PET/CT was able to clearly identify 12 types of malignant tumours with favourable tumour-to-background contrast, which resulted in a higher detection rate of primary tumours than did [18F] FDG PET/CT (98.2% vs. 82.1%, P = 0.021). Meanwhile, [68Ga]Ga-DOTA-FAPI-04 PET/CT showed a better sensitivity than [18F] FDG PET/CT in the detection of lymph nodes (86.4% vs. 45.5%, P = 0.004) and bone and visceral metastases (83.8% vs. 59.5%, P = 0.004). Conclusion: [68Ga]Ga-DOTA-FAPI-04 PET/CT showed a superior diagnostic efficacy than [18F] FDG PET/CT for the diagnosis of primary and metastatic lesions in patients with various types of cancer, especially in identifying liver metastases, peritoneal carcinomatosis, and brain tumours. [ABSTRACT FROM AUTHOR]