1. Academic Validation
  2. Synthesis, Preclinical Evaluation, and First-in-Human PET Study of [68Ga]-Labeled Biphenyl-Containing PSMA Tracers

Synthesis, Preclinical Evaluation, and First-in-Human PET Study of [68Ga]-Labeled Biphenyl-Containing PSMA Tracers

  • J Med Chem. 2023 Sep 28;66(18):13332-13345. doi: 10.1021/acs.jmedchem.3c01475.
Yimin Chen 1 Xiaojun Zhang 2 Ming Ni 3 Xi Gao 1 Xinlin Wang 1 Qiang Xie 3 Jinming Zhang 2 Mengchao Cui 1 4
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 Department of Nuclear Medicine, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei 230001, China.
  • 4 Center for Advanced Materials Research, Beijing Normal University at Zhuhai, Zhuhai 519087, China.
Abstract

Radioisotope-labeled prostate-specific membrane antigen (PSMA) PET tracers have gained popularity in diagnosing prostate Cancer (PCa). This study aimed to improve the affinity and tumor-targeting capabilities of new PSMA tracers by increasing the number of pharmacophores that specifically bind to PSMA. Using biphenyl as a core scaffold, we investigated the relationship among spacer segments, affinity, and pharmacokinetic properties. In preclinical PET studies on mice with 22Rv1 tumors, compared with [68Ga]Ga-PSMA-11 (SUVmax = 3.37), [68Ga]Ga-PSMA-D5 (Ki = 0.15) showed higher tumor uptake (SUVmax = 3.51) and lower renal uptake (T/K = 1.84). In the first-in-human study, [68Ga]Ga-PSMA-D5 effectively detected small PCa-associated lesions and distant metastases. The advantages of [68Ga]Ga-PSMA-D5 include high tumor uptake, straightforward synthesis, and labeling, making it a promising PSMA PET tracer. Furthermore, [68Ga]Ga-PSMA-D5 contains a DOTA chelator, allowing convenient labeling with therapeutic radionuclides such as 177Lu and 225Ac, providing the potential for targeted radioligand therapy in PCa.

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