1. Academic Validation
  2. Synthesis, Preclinical Evaluation, and First-in-Human PET Study of Quinoline-Containing PSMA Tracers with Decreased Renal Excretion

Synthesis, Preclinical Evaluation, and First-in-Human PET Study of Quinoline-Containing PSMA Tracers with Decreased Renal Excretion

  • J Med Chem. 2021 Apr 8;64(7):4179-4195. doi: 10.1021/acs.jmedchem.1c00117.
Xiaojun Zhang 1 2 Yitian Wu 2 Qi Zeng 1 Tianxin Xie 1 Shulin Yao 2 Jinming Zhang 2 Mengchao Cui 1 3
Affiliations

Affiliations

  • 1 Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.
  • 2 Department of Nuclear Medicine, Chinese PLA General Hospital, Beijing 100853, China.
  • 3 Center for Advanced Materials Research, Advanced Institute of Natural Sciences, Beijing Normal University at Zhuhai, Zhuhai 519087, China.
Abstract

The prostate-specific membrane antigen (PSMA) is considered to be an excellent theranostic target of prostate Cancer (PCa). In this study, three 18F-labeled PSMA tracers with a more lipophilic quinoline functional spacer were designed, synthesized, and evaluated based on the Glu-Ureido-Lys binding motif. The effect of structure-related lipophilic difference on distribution and excretion of these tracers in vitro and in vivo (cells, rodent, primate, and human) was investigated by comparing with [18F]DCFPyL. There is no significant correlation between the renal elimination and the lipophilicity of the tracers in all species. However, the higher the lipophilicity of tracer, the higher the radioactivity accumulation in the liver of primate and human, and the less radioactivity is to excrete to the bladder with urine. The screened tracer [18F]8c, with a Ki value of 4.58 nM, displayed notable low bladder retention and demonstrated good imaging properties in patients with PCa.

Figures
Products