[en] 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.
Disciplines :
Chemistry Endocrinology, metabolism & nutrition Radiology, nuclear medicine & imaging
Author, co-author :
Sander, Kerstin ; Centre for Radiopharmaceutical Chemistry, University College London, 5 Gower Place, London WC1E 6BS, U.K
Gendron, Thibault ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique-nucléaire ; Centre for Radiopharmaceutical Chemistry, University College London, 5 Gower Place, London WC1E 6BS, U.K
Cybulska, Klaudia A; Centre for Radiopharmaceutical Chemistry, University College London, 5 Gower Place, London WC1E 6BS, U.K
Sirindil, Fatih; Centre for Radiopharmaceutical Chemistry, University College London, 5 Gower Place, London WC1E 6BS, U.K
Zhou, Junhua; William Harvey Research Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, U.K
Kalber, Tammy L; Centre for Advanced Biomedical Imaging, University College London, 72 Huntley Street, London WC1E 6DD, U.K
Lythgoe, Mark F; Centre for Advanced Biomedical Imaging, University College London, 72 Huntley Street, London WC1E 6DD, U.K
Kurzawinski, Tom R; NIHR University College London Hospitals Biomedical Research Centre, 149 Tottenham Court Road, London W1T 7DN, U.K
Brown, Morris J; William Harvey Research Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, U.K
Williams, Bryan; NIHR University College London Hospitals Biomedical Research Centre, 149 Tottenham Court Road, London W1T 7DN, U.K ; Institute of Cardiovascular Sciences, University College London, Gower Street, London WC1E 6BT, U.K
Årstad, Erik ; Centre for Radiopharmaceutical Chemistry, University College London, 5 Gower Place, London WC1E 6BS, U.K
Language :
English
Title :
Development of [18F]AldoView as the First Highly Selective Aldosterone Synthase PET Tracer for Imaging of Primary Hyperaldosteronism.
FP7 - 602102 - EPITARGET - Targets and biomarkers for antiepileptogenesis
Name of the research project :
Efficacy and Mechanism Evaluation Programme
Funders :
Barts Charity MRC - Medical Research Council University College London Hospitals NHS Foundation Trust UCL - University College London Wellcome Trust EC - European Commission
Funding text :
The research was funded by UCL Business (HF5E PoC-13-003; T.G.), the Wellcome Trust (102407/Z/13/Z; K.A.C.), the NIHR University College London Hospitals (UCLH) Biomedical Research Centre (BRC) (F.S.), the Medical Research Council (MR/T005769/1; F.S.), the NIHR BRC at Barts and The London School of Medicine and Dentistry, the NIHR EME Programme (14/145/09), Barts and the London Charity (MGU0360), and the European Union’s Seventh Framework Programme (FP7/2007–2013, grant 602102; T.G.). K.S. is funded by Mallinckrodt Pharmaceuticals. B.W. is funded by the NIHR UCLH BRC. The work was undertaken at the UCL Centre for Radiopharmaceutical Chemistry (CRC), which is funded in part by the NIHR UCLH BRC.The research was funded by UCL Business (HF5E PoC-13-003; T.G.), the Wellcome Trust (102407/Z/13/Z; K.A.C.), the NIHR University College London Hospitals (UCLH) Biomedical Research Centre (BRC) (F.S.) the Medical Research Council (MR/T005769/1; F.S.), the NIHR BRC at Barts and The London School of Medicine and Dentistry, the NIHR EME Programme (14/145/09), Barts and the London Charity (MGU0360), and the European Union's Seventh Framework Programme (FP7/2007-2013 grant 602102; T.G.). K.S. is funded by Mallinckrodt Pharmaceuticals. B.W. is funded by the NIHR UCLH BRC. The work was undertaken at the UCL Centre for Radiopharmaceutical Chemistry (CRC), which is funded in part by the NIHR UCLH BRC.
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