A novel CYP11B2-specific imaging agent for detection of unilateral subtypes of primary aldosteronism

Tsutomu Abe, Mitsuhide Naruse, William F. Young, Nobuya Kobashi, Yoshihiro Doi, Akihiro Izawa, Kei Akama, Yuki Okumura, Miho Ikenaga, Hiroyuki Kimura, Hideo Saji, Kuniaki Mukai, Hiroki Matsumoto

Research output: Contribution to journalArticle

22 Citations (Scopus)

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. 11Cmetomidate (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 18F-CDP2230, a new imaging agent, for CYP11B2 over CYP11B1 and determine whether the biodistribution profile of 18F-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 18F-CDP2230 to CYP11B2-expressing regions. Furthermore, positron emission tomography and magnetic resonance imaging were performed to evaluate the biodistribution of 18F-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 18F-CDP2230 to CYP11B2-expressing regions in the adrenal gland was more specific than that of 123I-IMTO. Moreover, the biodistribution study showed that 18F-CDP2230 accumulated in adrenal glands with low background uptake. Conclusions: Our study showed a high selectivity of 18F-CDP2230 for CYP11B2 over CYP11B1 with a favorable biodistribution for imaging CYP11B2. 18F-CDP2230 is a promising imaging agent for detecting unilateral subtypes of primary aldosteronism.

Original languageEnglish
Pages (from-to)1008-1015
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume101
Issue number4
DOIs
Publication statusPublished - 2016 Mar 1

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Cytochrome P-450 CYP11B2
Hyperaldosteronism
Steroid 11-beta-Hydroxylase
Imaging techniques
Positron emission tomography
Adrenal Glands
Autoradiography
Positron-Emission Tomography
Veins
CDP2230
Sampling
Magnetic resonance
Aldosterone
Adenoma
Inhibitory Concentration 50
Rats

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

A novel CYP11B2-specific imaging agent for detection of unilateral subtypes of primary aldosteronism. / Abe, Tsutomu; Naruse, Mitsuhide; Young, William F.; Kobashi, Nobuya; Doi, Yoshihiro; Izawa, Akihiro; Akama, Kei; Okumura, Yuki; Ikenaga, Miho; Kimura, Hiroyuki; Saji, Hideo; Mukai, Kuniaki; Matsumoto, Hiroki.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 101, No. 4, 01.03.2016, p. 1008-1015.

Research output: Contribution to journalArticle

Abe, T, Naruse, M, Young, WF, Kobashi, N, Doi, Y, Izawa, A, Akama, K, Okumura, Y, Ikenaga, M, Kimura, H, Saji, H, Mukai, K & Matsumoto, H 2016, 'A novel CYP11B2-specific imaging agent for detection of unilateral subtypes of primary aldosteronism', Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 4, pp. 1008-1015. https://doi.org/10.1210/jc.2015-3431
Abe, Tsutomu ; Naruse, Mitsuhide ; Young, William F. ; Kobashi, Nobuya ; Doi, Yoshihiro ; Izawa, Akihiro ; Akama, Kei ; Okumura, Yuki ; Ikenaga, Miho ; Kimura, Hiroyuki ; Saji, Hideo ; Mukai, Kuniaki ; Matsumoto, Hiroki. / A novel CYP11B2-specific imaging agent for detection of unilateral subtypes of primary aldosteronism. In: Journal of Clinical Endocrinology and Metabolism. 2016 ; Vol. 101, No. 4. pp. 1008-1015.
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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. 11Cmetomidate (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 18F-CDP2230, a new imaging agent, for CYP11B2 over CYP11B1 and determine whether the biodistribution profile of 18F-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 18F-CDP2230 to CYP11B2-expressing regions. Furthermore, positron emission tomography and magnetic resonance imaging were performed to evaluate the biodistribution of 18F-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 18F-CDP2230 to CYP11B2-expressing regions in the adrenal gland was more specific than that of 123I-IMTO. Moreover, the biodistribution study showed that 18F-CDP2230 accumulated in adrenal glands with low background uptake. Conclusions: Our study showed a high selectivity of 18F-CDP2230 for CYP11B2 over CYP11B1 with a favorable biodistribution for imaging CYP11B2. 18F-CDP2230 is a promising imaging agent for detecting unilateral subtypes of primary aldosteronism.",
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T1 - A novel CYP11B2-specific imaging agent for detection of unilateral subtypes of primary aldosteronism

AU - Abe, Tsutomu

AU - Naruse, Mitsuhide

AU - Young, William F.

AU - Kobashi, Nobuya

AU - Doi, Yoshihiro

AU - Izawa, Akihiro

AU - Akama, Kei

AU - Okumura, Yuki

AU - Ikenaga, Miho

AU - Kimura, Hiroyuki

AU - Saji, Hideo

AU - Mukai, Kuniaki

AU - Matsumoto, Hiroki

PY - 2016/3/1

Y1 - 2016/3/1

N2 - 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. 11Cmetomidate (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 18F-CDP2230, a new imaging agent, for CYP11B2 over CYP11B1 and determine whether the biodistribution profile of 18F-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 18F-CDP2230 to CYP11B2-expressing regions. Furthermore, positron emission tomography and magnetic resonance imaging were performed to evaluate the biodistribution of 18F-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 18F-CDP2230 to CYP11B2-expressing regions in the adrenal gland was more specific than that of 123I-IMTO. Moreover, the biodistribution study showed that 18F-CDP2230 accumulated in adrenal glands with low background uptake. Conclusions: Our study showed a high selectivity of 18F-CDP2230 for CYP11B2 over CYP11B1 with a favorable biodistribution for imaging CYP11B2. 18F-CDP2230 is a promising imaging agent for detecting unilateral subtypes of primary aldosteronism.

AB - 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. 11Cmetomidate (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 18F-CDP2230, a new imaging agent, for CYP11B2 over CYP11B1 and determine whether the biodistribution profile of 18F-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 18F-CDP2230 to CYP11B2-expressing regions. Furthermore, positron emission tomography and magnetic resonance imaging were performed to evaluate the biodistribution of 18F-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 18F-CDP2230 to CYP11B2-expressing regions in the adrenal gland was more specific than that of 123I-IMTO. Moreover, the biodistribution study showed that 18F-CDP2230 accumulated in adrenal glands with low background uptake. Conclusions: Our study showed a high selectivity of 18F-CDP2230 for CYP11B2 over CYP11B1 with a favorable biodistribution for imaging CYP11B2. 18F-CDP2230 is a promising imaging agent for detecting unilateral subtypes of primary aldosteronism.

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