Development of [18F]AldoView as the First Highly Selective Aldosterone Synthase PET Tracer for Imaging of Primary Hyperaldosteronism

• Published in: Journal of medicinal chemistry Vol. 64; no. 13; pp. 9321 - 9329
• Main Authors: Sander, Kerstin, Gendron, Thibault, Cybulska, Klaudia A, Sirindil, Fatih, Zhou, Junhua, Kalber, Tammy L, Lythgoe, Mark F, Kurzawinski, Tom R, Brown, Morris J, Williams, Bryan, Årstad, Erik
• Format: Journal Article Web Resource
• Language: English
• Published: American Chemical Society 08-07-2021
• Subjects: Chemistry; Chimie; Cytochrome P-450 CYP11B2/analysis; Cytochrome P-450 CYP11B2/antagonists & inhibitors; Cytochrome P-450 CYP11B2/metabolism; Cytochrome P-450 Enzyme Inhibitors/chemical synthesis; Cytochrome P-450 Enzyme Inhibitors/chemistry; Cytochrome P-450 Enzyme Inhibitors/pharmacology; Drug Development; Drug Discovery; Endocrinologie, métabolisme & nutrition; Endocrinology, metabolism & nutrition; Fluorine Radioisotopes; Fluorine-18; Human health sciences; Hyperaldosteronism; Hyperaldosteronism/diagnostic imaging; Hyperaldosteronism/drug therapy; Hyperaldosteronism/metabolism; Molecular Medicine; Physical, chemical, mathematical & earth Sciences; Physique, chimie, mathématiques & sciences de la terre; Positron-Emission Tomography; Radiochemistry; Radiologie, médecine & imagerie nucléaire; Radiology, nuclear medicine & imaging; Sciences de la santé humaine; Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804; 1520-4804
• DOI: 10.1021/acs.jmedchem.1c00539

The purpose of this study was to synthesize a fluorine-18 labeled, highly selective aldosterone synthase (hCYP11B2) inhibitor, [18F]­AldoView, and to assess its potential for the detection of aldosterone-producing adenomas (APAs) with positron emission tomography in patients with primary hyperaldosteronism (PHA). Using dibenzothiophene sulfonium salt chemistry, [18F]­AldoView was obtained in high radiochemical yield in one step from [18F]­fluoride. In mice, the tracer showed a favorable pharmacokinetic profile, including rapid distribution and clearance. Imaging in the adrenal tissue from patients with PHA revealed diffuse binding patterns in the adrenal cortex, avid binding in some adenomas, and “hot spots” consistent with aldosterone-producing cell clusters. The binding pattern was in good visual agreement with the antibody staining of hCYP11B2 and distinguished areas with normal and excessive hCYP11B2 expression. Taken together, [18F]­AldoView is a promising tracer for the detection of APAs in patients with PHA.