[68Ga]Ga-DATA5m.SA.FAPi PET/CT: Specific Tracer-uptake in Focal Nodular Hyperplasia and potential Role in Liver Tumor Imaging

Abstract

Fibroblast activating protein (FAP) is a membrane bound serine protease up-regulated in activated fibroblasts. These are essential for tissue remodeling in wound healing, chronic inflammation as well as in carcinoma associated fibroblasts (CAF) in several types of cancer [1] [2] [5] [8] [9] [11]. Subject of recent developments are new 68Ga-labelled PET tracers that operate as FAP-specific enzyme inhibitors (FAPi). The inhibitor is a small molecule based on a 4.4-difluoroproline-quinoline motif with a carbonitrile warhead that binds to FAP and blocks its chemical reaction. This highly potent inhibitor, referred to as UAMC 1110, combines high affinity respectively high inhibition ability to FAP and in opposite towards DPPs and PREP [6]. Various tumors and proliferating tissue show an uptake of this tracer. FAPi shows rapid washout from normal tissue facilitating high-contrast images. This is particularly advantageous as the sensitivity of FDG-PET is low in regions with high or inhomogenous glucose metabolism such as brain, heart or the liver [4]. Therefore, FAPi-PET may be superior to FDG-PET in these regions. The new class of FAPi-radiopharmaceuticals utilizes a squaric acid (SA) motif as part of the structure connecting the inhibitor moiety UAMC 1110 with various chelators such as DOTA and DATA, yielding precursors of type DOTA.SA.FAPi or DATA5m.SA.FAPi. All compounds are of low nanomolar binding affinity to FAP and excellent selectivity towards other proteases [3].