Tsutomu Abe1, Mitsuhide Naruse1, William F Young1, Nobuya Kobashi1, Yoshihiro Doi1, Akihiro Izawa1, Kei Akama1, Yuki Okumura1, Miho Ikenaga1, Hiroyuki Kimura1, Hideo Saji1, Kuniaki Mukai1, Hiroki Matsumoto1. 1. Research Center (T.A., N.K., Y.D., A.I., K.A., Y.O., M.I., H.M.), Nihon Medi-Physics Co. Ltd., Chiba, 299-0266 Japan; Department of Endocrinology, Metabolism and Hypertension (M.N.), National Hospital Organization Kyoto Medical Center, Kyoto, 612-8555 Japan; Division of Endocrinology, Diabetes, Metabolism and Nutrition (W.F.Y.), Department of Internal Medicine, Mayo Clinic, Rochester, MN 55902; Department of Patho-Functional Bioanalysis (H.K., H.S.), Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501 Japan; and Department of Biochemistry (K.M.) and Medical Education Center (K.M.), Keio University School of Medicine, Tokyo, 160-8582 Japan.
Abstract
CONTEXT: Although adrenal vein sampling is the standard method to distinguish unilateral from bilateral forms of primary aldosteronism, it is an invasive and technically difficult procedure. (11)C-metomidate (MTO)-positron emission tomography was reported as a potential replacement for adrenal vein sampling. However, MTO has low selectivity for CYP11B2 over CYP11B1. OBJECTIVE: This study aimed to determine the selectivity of (18)F-CDP2230, a new imaging agent, for CYP11B2 over CYP11B1 and determine whether the biodistribution profile of (18)F-CDP2230 is favorable for imaging CYP11B2. METHODS: The IC50 of CDP2230 for the enzymatic activities of CYP11B2 and CYP11B1 was determined using cells with stable expression of either enzyme. In vitro autoradiography of human adrenal sections with aldosterone-producing adenomas was performed to confirm the specific binding ability of (18)F-CDP2230 to CYP11B2-expressing regions. Furthermore, positron emission tomography and magnetic resonance imaging were performed to evaluate the biodistribution of (18)F-CDP2230 in rats. RESULTS: Although CDP2230 showed a significantly lower affinity for CYP11B2 and CYP11B1 than did MTO analogues, its selectivity for CYP11B2 over CYP11B1 was higher than that of MTO analogues. In vitro autoradiography revealed that the binding of (18)F-CDP2230 to CYP11B2-expressing regions in the adrenal gland was more specific than that of (123)I-IMTO. Moreover, the biodistribution study showed that (18)F-CDP2230 accumulated in adrenal glands with low background uptake. CONCLUSIONS: Our study showed a high selectivity of (18)F-CDP2230 for CYP11B2 over CYP11B1 with a favorable biodistribution for imaging CYP11B2. (18)F-CDP2230 is a promising imaging agent for detecting unilateral subtypes of primary aldosteronism.
CONTEXT: Although adrenal vein sampling is the standard method to distinguish unilateral from bilateral forms of primary aldosteronism, it is an invasive and technically difficult procedure. (11)C-metomidate (MTO)-positron emission tomography was reported as a potential replacement for adrenal vein sampling. However, MTO has low selectivity for CYP11B2 over CYP11B1. OBJECTIVE: This study aimed to determine the selectivity of (18)F-CDP2230, a new imaging agent, for CYP11B2 over CYP11B1 and determine whether the biodistribution profile of (18)F-CDP2230 is favorable for imaging CYP11B2. METHODS: The IC50 of CDP2230 for the enzymatic activities of CYP11B2 and CYP11B1 was determined using cells with stable expression of either enzyme. In vitro autoradiography of human adrenal sections with aldosterone-producing adenomas was performed to confirm the specific binding ability of (18)F-CDP2230 to CYP11B2-expressing regions. Furthermore, positron emission tomography and magnetic resonance imaging were performed to evaluate the biodistribution of (18)F-CDP2230 in rats. RESULTS: Although CDP2230 showed a significantly lower affinity for CYP11B2 and CYP11B1 than did MTO analogues, its selectivity for CYP11B2 over CYP11B1 was higher than that of MTO analogues. In vitro autoradiography revealed that the binding of (18)F-CDP2230 to CYP11B2-expressing regions in the adrenal gland was more specific than that of (123)I-IMTO. Moreover, the biodistribution study showed that (18)F-CDP2230 accumulated in adrenal glands with low background uptake. CONCLUSIONS: Our study showed a high selectivity of (18)F-CDP2230 for CYP11B2 over CYP11B1 with a favorable biodistribution for imaging CYP11B2. (18)F-CDP2230 is a promising imaging agent for detecting unilateral subtypes of primary aldosteronism.
Authors: Finn Holler; Daniel A Heinrich; Christian Adolf; Benjamin Lechner; Martin Bidlingmaier; Graeme Eisenhofer; Tracy Ann Williams; Martin Reincke Journal: Curr Hypertens Rep Date: 2019-09-03 Impact factor: 5.369
Authors: Lucie S Meyer; Xiao Wang; Eva Sušnik; Jacopo Burrello; Alessio Burrello; Isabella Castellano; Graeme Eisenhofer; Francesco Fallo; Gregory A Kline; Thomas Knösel; Tomaz Kocjan; Jacques W M Lenders; Paolo Mulatero; Mitsuhide Naruse; Tetsuo Nishikawa; Mirko Peitzsch; Lars C Rump; Felix Beuschlein; Stefanie Hahner; Celso E Gomez-Sanchez; Martin Reincke; Tracy Ann Williams Journal: Hypertension Date: 2018-09 Impact factor: 10.190
Authors: Iosif A Mendichovszky; Andrew S Powlson; Roido Manavaki; Franklin I Aigbirhio; Heok Cheow; John R Buscombe; Mark Gurnell; Fiona J Gilbert Journal: Diagnostics (Basel) Date: 2016-11-18
Authors: Yuhong Yang; Jacopo Burrello; Alessio Burrello; Graeme Eisenhofer; Mirko Peitzsch; Martina Tetti; Thomas Knösel; Felix Beuschlein; Jacques W M Lenders; Paolo Mulatero; Martin Reincke; Tracy Ann Williams Journal: J Steroid Biochem Mol Biol Date: 2019-01-14 Impact factor: 4.292
Authors: Kerstin Sander; Thibault Gendron; Klaudia A Cybulska; Fatih Sirindil; Junhua Zhou; Tammy L Kalber; Mark F Lythgoe; Tom R Kurzawinski; Morris J Brown; Bryan Williams; Erik Årstad Journal: J Med Chem Date: 2021-06-17 Impact factor: 7.446