FAPI-PET/CT: biodistribution and preliminary dosimetry estimate of two DOTA-containing FAP-targeting agents in patients with various cancers

Purpose: Fibroblast activation protein (FAP) is overexpressed in cancer associated fibroblasts of several tumor entities. Recent development of quinoline based positron-emission-tomography (PET)-tracers that act as FAP-Inhibitors (FAPI) demonstrated promising results preclinically and already also in few clinical cases. Consecutively this novel tracer is now applied in our hospital to amend the diagnostics of cancer patients facing limitations of standard exams. Here we analyze the tissue biodistribution and preliminary dosimetry of two members of this new class of PET-radiopharmaceuticals. Methods: A preliminary dosimetry estimate for FAPI-02 and FAPI-04 was based on two patients examined at 0.2h, 1h and 3h after tracer injection using the QDOSE dosimetry software suit. Further PET/CT scans of tumor patients were acquired 1 h after injection of either FAPI-02 (n=25) or FAPI-04 (n=25); for 6 patients an intra-individual related FDG-scan (also acquired 1h p.i.) was available. For the normal tissue of 16 organs, a 2 cm Spheric-VOI was placed in the parenchyma, for tumor lesions a threshold segmented VOI was used to quantify SUV mean/max . Results: Very similar to literature values for 18 F-FDG, 68 Ga-DOTATATE or 68 Ga-PSMA-11, an exam with 200 MBq 68 Ga-FAPI-2/4 corresponds to an equivalent dose of approx. 3-4 mSv. After a fast clearance via the kidneys the normal organs showed a low tracer uptake with only minimal changes between 10 min and 3 h p.i.. In FAPI-02 the tumor uptake from 1h to 3h p.i. decreased by 75%, whereas the tumor retention was prolonged with FAPI-04 (25% washout). Regarding tumor-to-background ratios, at 1h p.i. both FAPI-tracers performed equally. In comparison to FDG the tumor uptake was almost equal (average SUV max -FDG 7.41; SUV max -FAPI-2