Automated radiochemical synthesis of [68Ga]Ga-FAPI-4 employing modular lab standard with fixed-tubing non-cassette methodology: its preliminary clinical feasibility.

Abstract

Fully automated, multiple patient dose preparation of [68Ga]Ga-FAPI-4 was standardized using a commercial fixed tubing (non-cassette) based automated module namely Eckert and Ziegler 'Modular-Lab Standard' (EZ-ML). The routine production of [68Ga]Ga-FAPI-4 with consistent and reproducible decay corrected (dc) radiochemical yield (RCY) and radiochemical purity (RCP) of 97.47 ± 0.26% and 99.18 ± 0.34% respectively was achieved in our hospital radiopharmacy unit, which was effectively used in our high-volume Nuclear Medicine Centre (NMC). The quality control parameters of the produced [68Ga]Ga-FAPI-4 were in accordance with the European Pharmacopoeia. The promising pre-clinical in-vitro and in-vivo results demonstrated the potential of the product for clinical use in targeting Fibroblast Activation Protein (FAP) overexpressed tumors. Comparable IC50 values for FAPI-4 (6.12 nM) and [68Ga]Ga-FAPI-4 (6.52 nM) confirmed preservation of FAP inhibitory activity after radiolabeling. PET/CT image of SCID mouse bearing HT-1080 xenografted tumor, at 1h post-injection, clearly delineated the tumor. The high degree of localization of the produced [68Ga]Ga-FAPI-4 in FAP overexpressed tumors visualized in clinical PET/CT scan of patients, demonstrated its successful use for diagnostic scans of patients having FAP overexpressed solid tumors.