Translational imaging of the Fibroblast Activation Protein (FAP) using the new ligand Ga-68-OncoFAP-DOTAGA

Ziel/Aim The fibroblast activation protein (FAP) is an emerging target for molecular imaging and therapy in cancer[1]. OncoFAP is a novel small organic ligand for FAP with very high affinity[2]. In this translational study, we establish Ga-68-OncoFAP-DOTAGA (Ga-68-OncoFAP) radiolabeling, benchmark its properties in preclinical imaging and evaluate its application in clinical PET scanning.

Methodik/Methods Ga-68-OncoFAP was synthesized in a cassette-based fully automated labelling module. Lipophilicity, affinity, and serum stability of Ga-68-OncoFAP were assessed by determining logD7.4, IC₅₀ values and radiochemical purity.Ga-68-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 Ga-68-OncoFAP combined with PET/CT.

Ergebnisse/Results Ga-68-OncoFAP radiosynthesis was accomplished with high radiochemical yields. Affinity for FAP, lipophilicity and stability of Ga-68-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 Ga-68-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).

Schlussfolgerungen/Conclusions Excellent preclinical and clinical imaging characteristics validate Ga-68-OncoFAP as a powerful alternative to currently available FAP tracers.

Publikationsverlauf

Artikel online veröffentlicht:
14. April 2022

• Literatur/References

• 1 Backhaus P, Burg MC. et al. Radiology 2021 Oct 12: 204677
• 2 Millul J. et al. Proc National Acad Sci 2021; 118: e2101852118