TY - JOUR
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
N1 - Publisher Copyright:
© 2016 by the Endocrine Society.
PY - 2016/3
Y1 - 2016/3
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.
UR - http://www.scopus.com/inward/record.url?scp=84960918732&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84960918732&partnerID=8YFLogxK
U2 - 10.1210/jc.2015-3431
DO - 10.1210/jc.2015-3431
M3 - Article
C2 - 26756116
AN - SCOPUS:84960918732
SN - 0021-972X
VL - 101
SP - 1008
EP - 1015
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 3
ER -