Imaging of adrenal aldosterone synthase expression in patients with primary aldosteronism - a first-in-human study with [<SUP>18</SUP>F]aldoview PET-CT

Erik Arstad; Kerstin Sander; Tom Kurzawinski; Ramla Awais; Frazer Twyman; Dylan Pritchcard; Matthias Glaser; Esra Edaan; Fatih Sirindil; Yazead Buhidma; Robert Shortman; John Dickson; Cameron Anderson; Teng-Teng Chung; Tarek Abdel-Aziz; Morris Brown; Bryan Williams

doi:10.1530/endoabs.94.OC5.3

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Endocrine Abstracts (2023) 94 OC5.3 | DOI: 10.1530/endoabs.94.OC5.3

SFEBES2023 Oral Communications Adrenal and Cardiovascular (6 abstracts)

Imaging of adrenal aldosterone synthase expression in patients with primary aldosteronism – a first-in-human study with [¹⁸F]aldoview PET-CT

Erik Arstad ¹ , Kerstin Sander ¹ , Tom Kurzawinski ² , Ramla Awais ¹ , Frazer Twyman ¹ , Dylan Pritchcard ¹ , Matthias Glaser ¹ , Esra Edaan ¹ , Fatih Sirindil ¹ , Yazead Buhidma ¹ , Robert Shortman ² , John Dickson ² , Cameron Anderson ² , Teng-Teng Chung ² , Tarek Abdel-Aziz ^1,2 , Morris Brown ³ & Bryan Williams ^1,2

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¹UCL, London, United Kingdom. ²UCLH, London, United Kingdom. ³Queen Mary University of London, London, United Kingdom

Background: Primary aldosteronism (PA) is the most common potentially curable cause of secondary hypertension and is a risk factor for cardiovascular morbidity and mortality. For patients with unilateral disease adrenalectomy can be curative. However, PA remains substantially underdiagnosed due the complex diagnostic pathway required to identify patients with unilateral disease, and the difficulties in accurate lateralization of the affected adrenal gland. Specific and selective imaging of aldosterone synthase with PET-CT could provide a non-invasive readout of aldosterone production from both adrenals and allow patients with suspected PA to be better stratified for surgery or medical intervention. To achieve this, we have developed [¹⁸F]AldoView – the first highly selective aldosterone synthase PET tracer. Here we report the results of the first-in-human imaging with [¹⁸F]AldoView.

Methods: The PET ligand is a highly selective antagonist of aldosterone synthase with fluoride in its primary structure which enables labelling without structural modifications. [¹⁸F]AldoView was synthesized in accordance with Good Manufacturing Practice. Four patients (1F,3M) diagnosed with PA (RAA, saline infusion confirmatory test) with unilateral excessive aldosterone secretion confirmed by cross sectional imaging and Adrenal Venous Sampling were imaged with [¹⁸F]AldoView PET-CT prior to adrenalectomy.

Results: [¹⁸F]AldoView showed rapid clearance from background tissues and substantial uptake in the abnormal adrenal gland. The adrenal lateralisation index, measured as the SUVmax ratio between the two adrenals 35-45 min post-injection, was 6:1, 11:1, 4:1, and 7:1, suggesting it is markedly more selective relative to results reported with alternative PET tracers. Patients tolerated [¹⁸F]AldoView well and had no side effects.

Conclusion: PET/CT imaging with [¹⁸F]AldoView in this preliminary report of the first four patients has provided highly promising results and suggests that this highly selective tracer has potential to improve the stratification of patients with unilateral PA.