Repetitive Early⁶⁸Ga-FAPI PET Acquisition Comparing⁶⁸Ga-FAPI-02,⁶⁸Ga-FAPI-46, and⁶⁸Ga-FAPI-74: Methodologic and Diagnostic Implications for Malignant, Inflammatory/Reactive, and Degenerative Lesions

Abstract

Ga-labeled fibroblast activation protein (FAP) inhibitor ( 68 Ga-FAPI) PET targets 68 Ga-FAPI-positive activated fibroblasts and is a promising imaging technique for various types of cancer and nonmalignant pathologies. However, discrimination between malignant and nonmalignant 68 Ga-FAPI-positive lesions based on static PET with a single acquisition time point can be challenging. Additionally, the optimal imaging time point for 68 Ga-FAPI PET has not been identified yet, and different 68 Ga-FAPI tracer variants are currently used. In this retrospective analysis, we evaluate the diagnostic value of repetitive early 68 Ga-FAPI PET with 68 Ga-FAPI-02, 68 Ga-FAPI-46, and 68 Ga-FAPI-74 for malignant, inflammatory/reactive, and degenerative lesions and describe the implications for future 68 Ga-FAPI imaging protocols. Methods: Whole-body PET scans of 24 cancer patients were acquired at 10, 22, 34, 46, and 58 min after the administration of 150-250 MBq of 68 Ga-FAPI tracer molecules (8 patients each for 68 Ga-FAPI-02, 68 Ga-FAPI-46, and 68 Ga-FAPI-74). Detection rates and SUVs (SUV max and SUV mean ) for healthy tissues, cancer manifestations, and nonmalignant lesions were measured, and target-to-background ratios (TBR) versus blood and fat were calculated for all acquisition time points. Results: For most healthy tissues except fat and spinal canal, biodistribution analysis showed decreasing uptake over time. We analyzed 134 malignant, inflammatory/reactive, and degenerative lesions. Detection rates were minimally reduced for the first 2 acquisition time points and remained at a constant high level from 34 to 58 min after injection. The uptake of all 3 variants was higher in malignant and inflammatory/reactive lesions than in degenerative lesions. 68 Ga-FAPI-46 showed the highest uptake and TBRs in all pathologies. For all variants, TBRs versus blood constantly increased over time for all pathologies, and TBRs versus fat were constant or decreased slightly. Conclusion: 68 Ga-FAPI PET/CT is a promising imaging modality for malignancies and benign lesions. Repetitive early PET acquisition added diagnostic value for the discrimination of malignant from nonmalignant 68 Ga-FAPI-positive lesions. High detection rates and TBRs over time confirmed that PET acquisition earlier than 60 min after injection delivers high-contrast images. Additionally, considering clinical feasibility, acquisition at 30-40 min after injection might be a reasonable compromise. Different 68 Ga-FAPI variants show significant differences in timedependent biodistributional behavior and should be selected carefully depending on the clinical setting.

[68Ga]Ga-HBED-CC-FAPI Derivatives with Improved Radiolabeling and Specific Tumor Uptake

“…Since FAP inhibitors (FAPIs) are potentially useful for cancer therapy, FAP may also serve as a unique tumor-specific biomarker for diagnosis and therapy . Recent discoveries of radiolabeled FAPI derivatives have demonstrated high potential in cancer theranostics, and many clinical studies of FAPI tracers have been reported in the literature. − Among these reported FAPI imaging agents, [ 68 Ga]­Ga-DOTA-FAPI-04 (Figure ) is the most well-studied front runner. , …”

First Clinical Experience With [68Ga]Ga-FAPI-46-PET/CT Versus [18F]F-FDG PET/CT for Nodal Staging in Cervical Cancer

“…Recent studies suggest that image acquisition earlier than 60 minutes or even multiple-minute time points improve the discrimination of malignant lesions. 23 , 24 …”

“…Recent studies suggest that image acquisition earlier than 60 minutes or even multiple-minute time points improve the discrimination of malignant lesions. 23,24 The strength of the reported study is the 1:1 correlation of localization and histological confirmation of suspicious LNs by performing laparoscopic nodal staging after [ 68 Ga]Ga-FAPI-46 PET/CT and [ 18 F] F-FDG PET/CT. This study benefits from the fact that patients were in RT positioning, and immobilization devices were used for all imaging data (better comparability of both scans).…”

“…The knowledge and interpretation of these pitfalls are important in the management of incidental findings in patients referred for cancer staging indications. Recent studies suggest that image acquisition earlier than 60 minutes or even multiple-minute time points improve the discrimination of malignant lesions 23,24 …”

Comparison of 68Ga-FAPI and 18F-FDG PET/CT for the diagnosis of primary and metastatic lesions in abdominal and pelvic malignancies: A systematic review and meta-analysis

“…In recent years, FAP inhibitors (FAPIs) have become a new targeted molecular probe in nuclear medicine and have attracted much attention in cancer diagnosis and treatment. Currently, dozens of radiopharmaceuticals targeting FAP have been developed, such as FAPI-01, FAPI-2, FAPI-04, FAPI-42, FAPI-46, and FAPI-74 (15)(16)(17)(18). In a recent study, high-quality images were obtained using gallium-68-FAPI-04 positron emission tomography/computed tomography ( 68 Ga-FAPI-04 PET/CT) showing good biodistribution properties and a high tumor background ratio in 28 tumors, including abdominal and pelvic tumors (19).…”