Design, Synthesis, and Evaluation of 18F-Labeling CYP1B1 PET Tracer Based on 2-Phenylquinazolin

Jiajing Cai; Lan Yi; Zhu Xia; Xinyue Huang; Meixian Yang; Zhenghuan Zhao; Chenyang Gao; Hengyi Yang; Jiayuan Zhang; Zhiping Peng; Dachuan Qiu

doi:10.1016/j.bmcl.2023.129533

Design, Synthesis, and Evaluation of ¹⁸F-Labeling CYP1B1 PET Tracer Based on 2-Phenylquinazolin

Bioorg Med Chem Lett. 2023 Nov 15:96:129533. doi: 10.1016/j.bmcl.2023.129533. Epub 2023 Oct 21.

Authors

Jiajing Cai¹, Lan Yi¹, Zhu Xia², Xinyue Huang³, Meixian Yang¹, Zhenghuan Zhao¹, Chenyang Gao⁴, Hengyi Yang⁴, Jiayuan Zhang⁴, Zhiping Peng⁵, Dachuan Qiu⁶

Affiliations

¹ Department of Radiation Medicine, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.
² Department of Nuclear Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
³ College of Chemistry and Chemical Engineering, Chongqing University of Technology, Chongqing 400054, China.
⁴ Chongqing Yucai Secondary School, Chongqing 400050, China.
⁵ Department of Radiation Medicine, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China. Electronic address: pengzhiping@cqmu.edu.cn.
⁶ Department of Radiation Medicine, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China. Electronic address: 102899@cqmu.edu.cn.

PMID: 37865282
DOI: 10.1016/j.bmcl.2023.129533

Abstract

Cytochrome P450 (CYP)1B1 has been identified to be specifically overexpressed in several solid tumors, thus it's a potential target for the detection of tumors. Based on the 2-Phenylquinazolin CYP1B1 inhibitors, we designed and synthesized several positron emission computed tomography (PET) imaging probes targeting CYP1B1. Through IC₅₀ determinations, most of these probes exhibited good affinity and selectivity to CYP1B1. Considering their affinity, solubility, and their ¹⁸F labeling methods, we chose compound 5c as the best candidate. The ¹⁸F radiolabeling of [¹⁸F] 5c was easy to handle with good radiolabeling yield and radiochemical purity. In vitro and in vivo stability study indicated that probe [¹⁸F]5c has good stability. In cell binding assay, [¹⁸F]5c could be specifically taken up by tumor cells, especially HCT-116 cells. Although the tumor-blood (T/B) and tumor-muscle (T/M) values and PET imaging results were unsatisfied, it is still possible to develop PET probes targeting CYP1B1 by structural modification on the basis of 5c in the future.

Keywords: 2-Phenylquinazolin; CYP1B1; Cancer detection; PET tracer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Fluorine Radioisotopes
Positron-Emission Tomography* / methods
Radiopharmaceuticals* / chemistry
Radiopharmaceuticals* / pharmacology

Substances

Radiopharmaceuticals
Fluorine Radioisotopes