3BP-3940, a highly potent FAP-targeting peptide for theranostics - production, validation and first in human experience with Ga-68 and Lu-177

Abstract

Summary: Hardly any new tracers attracted more attention in nuclear medicine in the last couple of years than radiolabeled fibroblast activation protein inhibitors (FAPi’s). Molecules targeting cancer-associated fibroblasts (CAFs) or disease-associated fibroblasts in benign disorders (DAFs) gave rise to a new class of radiopharmaceuticals widely applicable for imaging and with the desired use as therapeutic compounds. Despite displaying benefits in diagnostic sensitivity over FDG, most FAP-targeting compounds in today’s clinical routine continue to lack therapeutic utility due to short tumor retention. In this study, we evaluated 3BP-3940, specifically designed for achieving prolonged tumor retention and remarkably low uptake in healthy tissues. We herein present the automated manufacturing of gallium-68 (Ga-68) and lutetium-177 (Lu-177)-labeled 3BP-3940, their respective in vitro stability, validation of an automated production process, and validation of an analytical HPLC method for quality control. Finally, we give a first insight into the clinical utility of the two compounds.

Keywords

• Nuclear medicine
• Pharmaceutical quality control
• Radiochemicals