SFEBES2021 Oral Communications Adrenal and Cardiovascular (6 abstracts)
Development of [18F]AldoView as the first highly selective aldosterone synthase PET tracer for imaging of patients with Primary Hyperaldosteronism.
Kerstin Sander 1 , Thibault Gendron 1 , Klaudia A. Cybulska 1 , Faith Sirindil 1 , Jonhua Zhou 1 , Tammy L. Kalber 1 , Mark F. Lythgoe 1 , Tom R. Kurzawinski 2 , Morris J. Brown 3 & Erik Arstad 1
1Centre for Radiopharmaceutical Chemistry, University College London, London, United Kingdom; 2Centre for Endocrine Surgery, University College London NHS Trust, London, United Kingdom; 3William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
Background: Inappropriately high aldosterone in patients with primary hyperaldosteronism (PHA) is due to increased aldosterone synthase (CYP11B2) activity. Selective in vivo imaging of overexpressed CYP11B2 in adrenals with positron emission tomography (PET) has not yet been achieved due to close homology of enzymes involved in aldosterone and cortisol (CYP11B1) synthesis.
Aim: Synthesize a fluorine-18 labelled highly selective CYP11B2 inhibitor, [18F]AldoView, and assess its potential for the detection of aldosterone producing adenomas (APAs) and aldosterone producing cell clusters (APCCs) with PET in patients with PHA.
Methods: [18F]AldoView was synthesised in high radiochemical yields using a proprietary radiochemistry platform.1 Dynamic PET/CT imaging, biodistribution studies and metabolite analysis was performed in wild type female BALB/c mice. [18F]AldoView binding to CYP11B2 was characterised by quantitative phosphorimaging in tissue sections prepared from adrenalectomy specimens of patients with PHA, Cushing, phaeochromocytoma and incidentaloma. CYP11B2 specific immunohistochemistry (IHC) was performed in directly adjacent sections.
Results: In mice, [18F]AldoView showed a favourable pharmacokinetic profile, including rapid distribution and clearance. In tissue sections, [18F]AldoView binding was visually consistent with CYP11B2 IHC staining. Specific tracer binding to CYP11B2 positive areas ranged from 8.6 to 19.1 kBq/cm2 and was evenly distributed across tissue identified as APA, in contrast to cortex, which had diffuse patterns with hot spots in keeping with APCCs. There was no evidence of elevated tracer uptake in CYP11B2 negative areas in patients with or without PHA (3.2±1.1 kBq/cm2 and 2.6±1.8 kBq/cm2, respectively).2
Conclusion: Our results strongly suggest that [18F]AldoView can image CYP11B2 expression in human adrenals and could become first highly selective radioactive tracer to be used to stratify patients with PHA for adrenalectomy.
References: 1. Gendron et al. J Am Chem Soc 2018,140,35,11125–11132.
2. Sander et al. J Med Chem 2021, epub ahead of print: doi.org/10.1021/acs.jmedchem.1c00539.
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