title: A Novel CYP11B2-Specific Imaging Agent for Detection of Unilateral Subtypes of Primary Aldosteronism.
abstract: BACKGROUND
  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.affiliation: 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.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Abe
authors.affiliation: 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.
authors.forename: Mitsuhide
authors.initials: M
authors.lastname: Naruse
authors.affiliation: 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.
authors.forename: William F
authors.initials: WF
authors.lastname: Young
authors.affiliation: 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.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Kobashi
authors.affiliation: 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.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Doi
authors.affiliation: 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.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Izawa
authors.affiliation: 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.
authors.forename: Kei
authors.initials: K
authors.lastname: Akama
authors.affiliation: 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.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Okumura
authors.affiliation: 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.
authors.forename: Miho
authors.initials: M
authors.lastname: Ikenaga
authors.affiliation: 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.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kimura
authors.affiliation: 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.
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
authors.affiliation: 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.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Mukai
authors.affiliation: 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.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Matsumoto
mesh_terms: D000236:Adenoma / Q000201:enzymology; D000310:Adrenal Gland Neoplasms / Q000201:enzymology; D000311:Adrenal Glands / Q000201:enzymology; D000450:Aldosterone / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001562:Benzimidazoles; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D019405:Cytochrome P-450 CYP11B2 / Q000032:analysis*; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D006929:Hyperaldosteronism / Q000145:classification* / Q000201:enzymology*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D011849:Radioactive Tracers; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D013252:Steroid 11-beta-Hydroxylase / Q000032:analysis
chemical_list: D001562:Benzimidazoles; C000609630:CDP2230; D005462:Fluorine Radioisotopes; D011849:Radioactive Tracers; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase