Synthesis and Evaluation of 99m Tc-Labeled l-Aspartic Acid as a EuK Polymer Linker for Targeting PSMA to a Novel SPECT Tumor Tracer.

Autor: Li Z; Key Laboratory of Radiopharmaceuticals of the Ministry of Education, College of Chemistry, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Beijing Normal University, Beijing 100875, P. R. China., Duan X; Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, P. R. China., Han P; Key Laboratory of Radiopharmaceuticals of the Ministry of Education, College of Chemistry, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Beijing Normal University, Beijing 100875, P. R. China., Yin G; Key Laboratory of Radiopharmaceuticals of the Ministry of Education, College of Chemistry, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Beijing Normal University, Beijing 100875, P. R. China., Jiang Y; Key Laboratory of Radiopharmaceuticals of the Ministry of Education, College of Chemistry, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Beijing Normal University, Beijing 100875, P. R. China.; Key Laboratory of Beam Technology of the Ministry of Education, College of Physics and Astronomy, Beijing Normal University, Beijing 100875, P. R. China., Ruan Q; Key Laboratory of Radiopharmaceuticals of the Ministry of Education, College of Chemistry, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Beijing Normal University, Beijing 100875, P. R. China.; Key Laboratory of Beam Technology of the Ministry of Education, College of Physics and Astronomy, Beijing Normal University, Beijing 100875, P. R. China., Zhang J; Key Laboratory of Radiopharmaceuticals of the Ministry of Education, College of Chemistry, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Beijing Normal University, Beijing 100875, P. R. China.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2024 Dec 12; Vol. 67 (23), pp. 21617-21628. Date of Electronic Publication: 2024 Dec 03.
DOI: 10.1021/acs.jmedchem.4c02656
Abstrakt: The development of novel tracers targeting prostate-specific membrane antigen (PSMA) has great potential for improving the diagnosis and treatment of prostate cancer (PCa). This study aimed to improve the absolute tumor uptake and tumor-to-background ratios (TBRs) of this novel PSMA tracer by increasing the number of pharmacophores, Glu-urea-Lys (EuK), that specifically bind to PSMA. We successfully synthesized four radioligands and prepared a total of 12 stable radiotracers by coordinating 99m Tc with various coligands. [ 99m Tc]Tc-EUKD-EDDA showed the best pharmacokinetic properties both in vitro and in vivo . It effectively increased the absolute uptake in tumors and resulted in good tumor retention. Rapid clearance in nontarget organs resulted in high TBRs. High-contrast SPECT/CT images were obtained within 2-6 h after injection, suggesting that [ 99m Tc]Tc-EUKD-EDDA has great application potential in time-lapse imaging of PCa, which is important for improving the diagnostic accuracy of PCa in clinical practice.
Databáze: MEDLINE
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