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

Kerstin Sander,Mark F Lythgoe,Erik Årstad,Fatih Sirindil,Klaudia A Cybulska,Bryan Williams,Tom R Kurzawinski,Morris J Brown,Thibault Gendron,Tammy L Kalber,Junhua Zhou

doi:10.1021/acs.jmedchem.1c00539

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.

Highlights

Hypertension is a leading cause of premature morbidity and death globally
Lifestyle changes and medication can be effective, elevated blood pressure due to secondary causes is more difficult to control and has greater morbidity. This is true for primary hyperaldosteronism (PHA), which is characterized by excessive, autonomous aldosterone production by the adrenals.[1]
PHA is a common type of secondary hypertension, which affects as much as 1% of the population, and causes significant morbidity and premature mortality due to both hypertension and the high levels of aldosterone

Summary

Introduction

Lifestyle changes and medication can be effective, elevated blood pressure due to secondary causes is more difficult to control and has greater morbidity. This is true for primary hyperaldosteronism (PHA), which is characterized by excessive, autonomous aldosterone production by the adrenals.[1] PHA occurs in 5−10% of patients with hypertension and in 15−25% of those with treatmentresistant hypertension.[2] PHA is a potentially curable cause of secondary hypertension, it is estimated that >99% of those with PHA remain undiagnosed and on lifelong medication at a high cost to individuals and healthcare budgets.[3] In most cases, PHA is due to either bilateral hyperplasia of the adrenal cortex or an aldosterone-producing adenoma (APA).

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