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

Abstract

Purpose The present study aims at evaluating the preclinical and the clinical performance of [68Ga]Ga-DATA5m.SA.FAPi, which has the advantage to be labeled with gallium-68 at room temperature. Methods [68Ga]Ga-DATA5m.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 [68Ga]Ga-DATA5m.SA.FAPi was conducted on six patients with prostate cancer, aiming on investigating, biodistribution, biokinetics, and determining tumor uptake. Results [68Ga]Ga-DATA5m.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 [68Ga]Ga-DATA5m.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 [68Ga]Ga-DATA5m.SA.FAPi as a diagnostic tool for FAP imaging.

Design, Preclinical Evaluation, and Clinical Translation of68Ga-FAPI-LM3, a Heterobivalent Molecule for PET Imaging of Nasopharyngeal Carcinoma

“…In our preliminary clinical PET study with 68 Ga-FAPI-LM3, it exhibited intense physiologic uptake in the blood, thyroid, pancreas, liver, kidney, and spleen. The existence of a soluble FAP form in plasma may explain the slow blood clearance in our preclinical and clinical data ( 25 , 26 ). Moreover, we speculate that the slow blood clearance may also be explained by the change in structure (from a monovalent to a divalent ligand) and the increase in molecular weight, which might affect the polarity of FAP/SSTR2-binding molecules (leading to increased lipophilicity).…”

Preparation of 18F-Labeled Tracers Targeting Fibroblast Activation Protein via Sulfur [18F]Fluoride Exchange Reaction

“…The 1 H, 13 C and 19 F NMR spectra provided were recorded on a Varian Inova-400 and J-values are given in Hertz (Hz). All radiochemistry experiments were performed at the Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR).…”

“…To date, several examples of radiolabeled FAP inhibitors (FAPIs) have been described [ 11 , 12 , 13 , 14 ]. The preparation of 68 Ga-labeled FAPIs has the advantage of utilizing a 68 Ge/ 68 Ga generator for tracer production, thereby negating the need for an on-site cyclotron and thus reducing tracer production costs.…”