Automated radiolabelling procedures for the preparation of OncoFAP-based radiopharmaceuticals for cancer imaging and therapy

Abstract

FAP-targeted radiopharmaceuticals represent a breakthrough in cancer imaging and a viable option for therapeutic applications. OncoFAP, an ultra-high affinity ligand of FAP, has been recently discovered and clinically validated for PET imaging procedures in patients with solid malignancies. While more and more clinical validation is becoming available, the need for scalable and robust procedures for the preparation of this new class of radiopharmaceuticals continues to increase. In this article, we present the development of automated radiolabelling procedures with FASTlab 2 for the preparation of OncoFAP-based radiopharmaceuticals for cancer imaging and therapy. A new series of [68Ga]Ga-OncoFAP, [177Lu]Lu-OncoFAP and [18F]AlF-OncoFAP was produced with high-yields. Chemical and biochemical characterization after radiolabelling confirmed excellent stability, retention of high affinity for FAP and absence of radiolysis by-products. The in vivo biodistribution of [18F]AlF-OncoFAP-NOTA, a candidate for PET imaging procedures in patients, was assessed in mice bearing FAP-positive solid tumours. The product showed rapid accumulation in solid tumours, with an average of 6.6% ID/g one hour after systemic administration and excellent tumour-to-healthy organs ratio. We have established methodologies to efficiently produce an OncoFAP-based radiotheranostic pair in which [68Ga]Ga-OncoFAP-DOTAGA is used as a companion diagnostic of the targeted therapeutic agent [177Lu]Lu-OncoFAP-DOTAGA Objectives: We have developed simple, quick, safe and robust synthetic procedures for the preparation of theranostic OncoFAP-compounds based on Gallium-68, Lutetium-177 and Alluminium-Fluoride-18 using the commercially available FASTlab 2 synthesis module.