An ACE2 PET imaging agent derived from 18F/Cl exchange of MLN-4760 under phase transfer catalysis

Pan Zhou; Kai Ning; Shuai Xue; Qingqing Li; Danni Li; Haijun Yang; Zeying Liang; Rou Li; Jian Yang; Xiao Li; Lan Zhang

doi:10.1186/s41181-024-00316-5

An ACE2 PET imaging agent derived from ¹⁸F/Cl exchange of MLN-4760 under phase transfer catalysis

EJNMMI Radiopharm Chem. 2024 Dec 2;9(1):83. doi: 10.1186/s41181-024-00316-5.

Authors

Pan Zhou^#^{1

2}, Kai Ning^#³, Shuai Xue², Qingqing Li³, Danni Li¹, Haijun Yang⁴, Zeying Liang⁴, Rou Li¹, Jian Yang⁵, Xiao Li^{6

7

8}, Lan Zhang⁹

Affiliations

¹ Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, 200433, China.
² Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China.
³ Artery Pharmaceuticals, Shanghai, 201413, China.
⁴ School of Medicine, Shanghai University, Shanghai, 200444, China.
⁵ School of Medicine, Shanghai University, Shanghai, 200444, China. yj_scu@163.com.
⁶ Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, 200433, China. lixiao@sinap.ac.cn.
⁷ Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China. lixiao@sinap.ac.cn.
⁸ Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China. lixiao@sinap.ac.cn.
⁹ Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China. zhanglan@sinap.ac.cn.

^# Contributed equally.

Abstract

Background: Angiotensin-converting enzyme-2 (ACE2) acts as a key regulatory molecule and important therapeutic target in the pathological remodeling of numerous organs and diseases. In this study, a rapid, simple, and efficient synthetic route with a catalytic, ¹⁸F-for-Cl (¹⁸F/Cl) exchange scheme was designed for the preparation of ¹⁸F-labeled MLN-4760, and its targeting ability was investigated in a humanized ACE2 mouse model.

Results: A novel ¹⁸F-labeled MLN-4760 radioligand, abbreviated as ¹⁸F-MLN-4760, was successfully synthesized by the ¹⁸F/Cl exchange-labeling, and was purified by SepPak C18 columns with a radiochemical yield of 30% and a radiochemical purity of 29.89%. Target distribution of ¹⁸F-MLN-4760 in several organs with high ACE2 expression was observed by PET imaging with good stability over 120 min. The biodistribution data showed that the uptake of ¹⁸F-MLN-4760 in ACE2-overexpressing organs and tissues was highly specific, and immunohistochemistry confirmed the same results of ACE2 expression and biodistribution in the major organs (heart, liver, lungs, and kidneys). There was a good correlation between the uptake in the organs with high ACE2 expression and ACE2 expression levels (r = 0.935).

Conclusion: ¹⁸F-MLN-4760 was successfully synthesized via ¹⁸F/Cl exchange under phase transfer catalysis, and served as a potential probe for ACE2-targeted PET imaging.

Keywords: 18F/Cl exchange; ACE2; MLN−4760; PET imaging agent; Phase transfer catalysis.

Abstract

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