[18F]ApaScan: A 2-Pyridinylbenzimidazole PET Tracer with Highly Selective Binding to Human Aldosterone-Producing Adenoma Tissue

Abstract Aldosterone synthase (CYP11B2) is overexpressed in aldosterone-producing adenomas (APAs) and represents a promising PET target for the noninvasive localization of APA lesions in primary aldosteronism. To address this need, we synthesized and evaluated 2-pyridinylbenzimidazole analogues for their ability to bind to human APA (hAPA) tissue. Based on initial binding assays, five analogues were selected and radiolabeled with fluorine-18 for autoradiographic and saturation binding studies. Among them, [18F]3 ([18F]ApaScan) exhibited high-affinity binding to hAPA homogenates (KD = 8.4 nM) with no measurable specific binding to normal adrenal (hNA) homogenates, demonstrating excellent tissue selectivity for hAPA over hNA. Quantitative autoradiography using [18F]3 further confirmed a high hAPA-to-hNA tissue binding ratio of 18. In normal rats, [18F]3 displayed rapid adrenal uptake, efficient clearance without prolonged retention, and no skeletal accumulation. Taken together, these results suggest that [18F]3 has the potential to be developed into a PET tracer for localizing APAs in primary aldosteronism.