Translational imaging of the fibroblast activation protein (FAP) using the new ligand [(68)Ga]Ga-OncoFAP-DOTAGA

PURPOSE: The fibroblast activation protein (FAP) is an emerging target for molecular imaging and therapy in cancer. OncoFAP is a novel small organic ligand for FAP with very high affinity. In this translational study, we establish [(68)Ga]Ga-OncoFAP-DOTAGA ((68)Ga-OncoFAP) radiolabeling, benchmark its properties in preclinical imaging, and evaluate its application in clinical PET scanning. METHODS: (68)Ga-OncoFAP was synthesized in a cassette-based fully automated labeling module. Lipophilicity, affinity, and serum stability of (68)Ga-OncoFAP were assessed by determining logD(7.4), IC(50) values, and radiochemical purity. (68)Ga-OncoFAP tumor uptake and imaging properties were assessed in preclinical dynamic PET/MRI in murine subcutaneous tumor models. Finally, biodistribution and uptake in a variety of tumor types were analyzed in 12 patients based on individual clinical indications that received 163 ± 50 MBq (68)Ga-OncoFAP combined with PET/CT and PET/MRI. RESULTS: (68)Ga-OncoFAP radiosynthesis was accomplished with high radiochemical yields. Affinity for FAP, lipophilicity, and stability of (68)Ga-OncoFAP measured are ideally suited for PET imaging. PET and gamma counting–based biodistribution demonstrated beneficial tracer kinetics and high uptake in murine FAP-expressing tumor models with high tumor-to-blood ratios of 8.6 ± 5.1 at 1 h and 38.1 ± 33.1 at 3 h p.i. Clinical (68)Ga-OncoFAP-PET/CT and PET/MRI demonstrated favorable biodistribution and kinetics with high and reliable uptake in primary cancers (SUV(max) 12.3 ± 2.3), lymph nodes (SUV(max) 9.7 ± 8.3), and distant metastases (SUV(max) up to 20.0). CONCLUSION: Favorable radiochemical properties, rapid clearance from organs and soft tissues, and intense tumor uptake validate (68)Ga-OncoFAP as a powerful alternative to currently available FAP tracers. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-021-05653-0.