Development of a CYP11B2 imaging tracer for primary aldosteronism: basic evaluation of iodine- and fluorine-incorporated pyridinyldihydroquinolinone derivatives.

IF 4.4 Q1 CHEMISTRY, INORGANIC & NUCLEAR

EJNMMI Radiopharmacy and Chemistry Pub Date : 2025-07-06 DOI:10.1186/s41181-025-00361-8

Yusuke Yagi, Hiroyuki Kimura, Riko Fuseda, Takaaki Murakami, Marina Omokawa, Kaito Ohta, Satoko Kise, Masakatsu Sone, Hiroyuki Yasui, Nobuya Inagaki, Hideo Saji

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Abstract

Background: Current methods for diagnosing primary aldosteronism (PA) are limited by their invasiveness and diagnostic accuracy. This study aimed to develop nuclear medicine imaging tracers targeting CYP11B2, which is overexpressed in patients with PA.

Results: We successfully synthesized iodinated and fluoroethoxynated pyridinyldihydroquinolinone (PDHQ) derivatives, among which PDHQ-1 exhibited the highest selectivity for CYP11B2. Furthermore, [¹²⁵I]PDHQ-1 accumulated in the adrenal gland soon after administration, reaching its highest saturation compared to that in other organs 5 min after administration; however, its radioactivity decreased over time. Autoradiographic analysis revealed that [¹²⁵I]PDHQ-1 displayed a 4.4-fold higher accumulation in the CYP11B2 region of adrenal sections from human patients with aldosterone-producing adenomas than in the CYP11B1 region. In contrast, [¹²⁵I]IMTO, which is a highly specific radiotracer for imaging adrenocortical tissue, displayed similar accumulation in the CYP11B2 and CYP11B1 regions.

Conclusions: Collectively, our results suggest that [¹²⁵I]PDHQ-1, featuring a pyridinyldihydroquinolinone scaffold, shows potential as an imaging tracer for PA.

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原发性醛固酮增多症CYP11B2显像示踪剂的研制：碘和氟结合吡啶基二氢喹啉酮衍生物的基本评价。

背景：目前诊断原发性醛固酮增多症（PA）的方法受其侵入性和诊断准确性的限制。本研究旨在开发针对在PA患者中过表达的CYP11B2的核医学成像示踪剂。结果：成功合成了碘化和氟乙氧基化吡啶基二氢喹啉酮（PDHQ）衍生物，其中PDHQ-1对CYP11B2的选择性最高。此外，[125I]PDHQ-1在给药后很快在肾上腺中积累，在给药后5分钟内达到最高饱和度。然而，它的放射性随着时间的推移而减弱。放射自显像分析显示，[125I]PDHQ-1在醛固酮产生腺瘤患者肾上腺切片CYP11B2区域的积累量比CYP11B1区域高4.4倍。相比之下，[125I]IMTO是一种高度特异性的肾上腺皮质组织成像放射性示踪剂，在CYP11B2和CYP11B1区域显示类似的积累。结论：总的来说，我们的研究结果表明，具有吡啶基二氢喹啉酮支架的[125I]PDHQ-1具有作为PA成像示踪剂的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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