2. Academic Validation
  3. Design, Synthesis, and Preclinical Evaluation of a Novel [18F]AlF-Labeling Positron Emission Tomography Tracer Targeting Prostate-Specific Membrane Antigen

Design, Synthesis, and Preclinical Evaluation of a Novel [18F]AlF-Labeling Positron Emission Tomography Tracer Targeting Prostate-Specific Membrane Antigen

  • J Med Chem. 2026 Feb 26;69(4):4888-4899. doi: 10.1021/acs.jmedchem.5c03590.
Yongqiang Zhang 1 2,  Jiawen Huang 3 4,  Yuqian Deng 3 4,  Zongtai Zheng 2,  Keyin Chen 3 4,  Gaoyuan Li 2,  Zhongxiang Zhao 2,  Xiaojun Zhang 3 4,  Ganghua Tang 3 4,  Xiaofu Qiu 1 2
Affiliations

Affiliations

  • 1 Department of Urology, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province 510317, China.
  • 2 Department of Urology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong Province 510317, China.
  • 3 Key Laboratory Project of Guangdong Provincial Department of Education for Ordinary Universities and GDMPA Key Laboratory for Quality Control and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province 510515, China.
  • 4 School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong Province 510515, China.
PMID: 41678292 DOI: 10.1021/acs.jmedchem.5c03590
Abstract

Prostate-specific membrane antigen (PSMA) is a promising target for the detection and treatment of prostate Cancer (PCa). However, current PSMA-targeting probes still exhibit suboptimal tumor uptake and retention, which limits their performance in positron emission tomography (PET) imaging of PCa. In this study, we developed a series of novel PSMA-targeting probes, among which NOTA-SP2A-PSMAL was selected. We then radiolabeled NOTA-SP2A-PSMAL with 18F and evaluated the in vitro and in vivo characteristics of [18F]AlF-SP2A-PSMAL. Subsequently, micro-PET/CT imaging and biodistribution studies were conducted in 22Rv1 and PC3 tumor-bearing mice to compare the in vivo distribution, tumor uptake, and retention of [18F]AlF-SP2A-PSMAL with [18F]AlF-PSMA-BCH. [18F]AlF-SP2A-PSMAL demonstrated favorable in vivo and in vitro properties. Micro-PET/CT imaging and biodistribution studies demonstrated that [18F]AlF-SP2A-PSMAL had satisfying pharmacokinetic characteristics and excellent targeting specificity for PSMA. Compared with [18F]AlF-PSMA-BCH, [18F]AlF-SP2A-PSMAL showed higher tumor uptake and better tumor retention. These results indicate that [18F]AlF-SP2A-PSMAL is a promising PET/CT tracer for diagnosing PCa.

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