Repetitive early FAPI-PET acquisition comparing FAPI-02, FAPI-46 and FAPI-74: methodological and diagnostic implications for malignant, inflammatory and degenerative lesions

Abstract

Purpose: FAPI-PET imaging targets FAP-positive, activated fibroblasts and is a promising imaging technique for various types of cancer and non-malignant pathologies. However, the discrimination between malignant and non-malignant FAPI-positive lesions based on static PET imaging with one acquisition timepoint can be challenging. Additionally, the optimal imaging timepoint for FAPI-PET has not been identified yet and even different FAPI tracer variants are currently used. In this retrospective analysis, we evaluate the diagnostic value of repetitive early FAPI-PET-imaging with FAPI-02, FAPI-46 and FAPI-74 for malignant, inflammatory and degenerative lesions and describe implications for future FAPI imaging protocols. Methods: Whole-body PET-Scans of 24 cancer patients were acquired at 10, 22, 34, 46 and 58 minutes after the administration of 150-250 MBq of ⁶⁸Ga-FAPI tracer molecules (8 Patients each regarding FAPI-02, FAPI-46 and FAPI-74). Detection rates and standardized uptake values (SUV_max and SUVmean) of healthy tissues, cancer manifestations and non-malignant lesions were measured and target-to-background ratios (TBR) versus blood and fat were calculated for all acquisition timepoints. Results: For most healthy tissues except fat and spinal canal, biodistribution analysis showed decreasing tracer uptake over time. 134 malignant, inflammatory/reactive and degenerative lesions were analysed. Detection rates were minimally reduced for the first two acquisition timepoints and remained on a constant high level from 34 to 58 minutes post injection (p.i.). The uptake of all three tracer variants was higher in malignant and inflammatory lesions than in degenerative lesions. FAPI-46 showed the highest uptake and TBRs in all pathologies. For all tracer variants, TBRs versus blood of all pathologies constantly increased over time and TBRs versus fat were constant or decreased slightly. Conclusion: 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 and non-malignant FAPI-positive lesions. High detection rates and TBRs over time confirm that PET acquisition at timepoints earlier than 60 minutes p.i. deliver high contrast images. Additionally, considering clinical feasibility, acquisition at 30 to 40 min p.i. could be a reasonable compromise. Different FAPI tracer variants show significant differences in their time-dependent biodistributional behaviour and should be selected carefully depending on the clinical setting.