68Ga-FAPI-46 PET for cancer imaging: A prospective single-arm clinical trial.

Abstract

3064 Background: Fibroblast activation protein (FAP) is expressed at high levels on tumor associated fibroblasts. FAP-directed radioligand positron-emission-tomography (FAP-PET) is a novel diagnostic tool for cancer. However, we currently do not understand the diagnostic performance of FAP-PET as compared to standard FDG-PET. Here we aim to compare tumor detection by FDG- vs. FAP-PET with independent validation of discrepant findings. Methods: Patients with (a) proven or suspected malignancy, (b) longest tumor diameter >1 cm, (c) intended surgery or biopsy, and (d) no prior external beam radiation or systemic tumor therapy within 3 months underwent FDG- and FAP-PET for tumor localization on subsequent days. Clinical reads were analyzed prospectively on a per-patient and per-region basis (local, locoregional nodal, distant organ or soft tissue, bone). Discrepant findings were validated as true vs. false positive by histopathology or image follow-up. Tracer uptake in tumor tissue was assessed by SUVmax. Results: In total n=100 patients (median 62 years, male/female n=68/32) underwent FDG- and FAP-PET. Five most frequent tumor entities and respective median FDG vs FAP uptake were RCC (n=19; SUVmax 8.4 vs. 7.1), sarcoma (n=18; 10.3 vs. 10.9), NSCLC (n=10; 12.4 vs. 13.7), lymphoma (n=9; 18.3 vs. 10.9), and PDAC (n=8; 4.1 vs. 7.3). On a per-patient basis, FDG- vs FAP-PET localized malignancy in n=93/94 patients. FDG- vs FAP-PET was concordant for the assessment of 362/400 (91%) regions. n=16/400 (4%) regions were negative on FDG- and positive on FAP-PET (88% true, 12% false positive). n=22/400 (6%) regions were negative on FAP- and positive on FDG-PET (57% true, 43% false positive). Two false positive FDG-PET findings were due to tracer uptake in reactive lymph nodes. There were no PET-related adverse events. Conclusions: In patients with various tumor entities, standard FDG- and novel FAP-PET localized tumor equally well. Additionally, FAP-PET was associated with a lower rate of false positive findings, especially in lymph node assessments. Clinical trial information: NCT05160051 . [Table: see text]