Translational assessment of a DATA-functionalized FAP inhibitor with facile (68)Ga-labeling at room temperature

PURPOSE: The present study aims at evaluating the preclinical and the clinical performance of [(68)Ga]Ga-DATA(5m.)SA.FAPi, which has the advantage to be labeled with gallium-68 at room temperature. METHODS: [(68)Ga]Ga-DATA(5m).SA.FAPi was assessed in vitro on FAP-expressing stromal cells, followed by biodistribution and in vivo imaging on prostate and glioblastoma xenografts. Moreover, the clinical assessment of [(68)Ga]Ga-DATA(5m).SA.FAPi was conducted on six patients with prostate cancer, aiming on investigating, biodistribution, biokinetics, and determining tumor uptake. RESULTS: [(68)Ga]Ga-DATA(5m).SA.FAPi is quantitatively prepared in an instant kit-type version at room temperature. It demonstrated high stability in human serum, affinity for FAP in the low nanomolar range, and high internalization rate when associated with CAFs. Biodistribution and PET studies in prostate and glioblastoma xenografts revealed high and specific tumor uptake. Elimination of the radiotracer mainly occurred through the urinary tract. The clinical data are in accordance with the preclinical data concerning the organ receiving the highest absorbed dose (urinary bladder wall, heart wall, spleen, and kidneys). Different to the small-animal data, uptake of [(68)Ga]Ga-DATA(5m).SA.FAPi in tumor lesions is rapid and stable and tumor-to-organ and tumor-to-blood uptake ratios are high. CONCLUSION: The radiochemical, preclinical, and clinical data obtained in this study strongly support further development of [(68)Ga]Ga-DATA(5m).SA.FAPi as a diagnostic tool for FAP imaging. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-023-06285-2.