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

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.