1. Development of [18F]AldoView as the First Highly Selective Aldosterone Synthase PET Tracer for Imaging of Primary Hyperaldosteronism
- Author
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Junhua Zhou, Tammy L. Kalber, Morris J. Brown, Fatih Sirindil, Tom R. Kurzawinski, Erik Årstad, Thibault Gendron, Klaudia A. Cybulska, Bryan Williams, Mark F. Lythgoe, and Kerstin Sander
- Subjects
Aldosterone synthase ,Fluorine Radioisotopes ,Cell ,01 natural sciences ,Article ,03 medical and health sciences ,Mice ,Structure-Activity Relationship ,Pharmacokinetics ,Drug Development ,Drug Discovery ,Hyperaldosteronism ,medicine ,Distribution (pharmacology) ,Animals ,Cytochrome P-450 CYP11B2 ,Cytochrome P-450 Enzyme Inhibitors ,Humans ,030304 developmental biology ,0303 health sciences ,Mice, Inbred BALB C ,medicine.diagnostic_test ,biology ,Dose-Response Relationship, Drug ,Molecular Structure ,Adrenal cortex ,Chemistry ,medicine.disease ,Molecular biology ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Dose–response relationship ,medicine.anatomical_structure ,Positron emission tomography ,Positron-Emission Tomography ,biology.protein ,Molecular Medicine ,Female - Abstract
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.
- Published
- 2021