{"title":"一种新的PSMA/ fap特异性放射性示踪剂99mtc - hpfsma用于PSMA阴性前列腺癌的诊断：从临床前验证到临床转化","authors":"Yuchen Wang, Xinru Li, Chenzhen Li, Huiyuan Xing, Rui Gao and Bing Jia*, ","doi":"10.1021/acs.jmedchem.5c01294","DOIUrl":null,"url":null,"abstract":"<p >In this study, we reported a bispecific radiotracer [<sup>99m</sup>Tc]Tc-HFaPSMA to improve the diagnostic sensitivity of prostate cancer (PCa). [<sup>99m</sup>Tc]Tc-HFaPSMA was prepared by <sup>99m</sup>Tc radiolabeling of a HYNIC-conjugated bispecific biomolecule HFaPSMA, which combines a PSMA-targeting motif (PhPSMA), a FAP-targeting ligand (GFAPI), a symmetric PEG<sub>4</sub>-N-bis(PEG<sub>4</sub>-acid) linker, and a chelator (HYNIC). Preclinical studies showed faster clearance and higher tumor uptake than that of its corresponding single-target radiotracers ([<sup>99m</sup>Tc]Tc-HPSMA and [<sup>99m</sup>Tc]Tc-HGFAPI). Clinical SPECT/CT matched the resolution of [<sup>18</sup>F]FDG and [<sup>18</sup>F]F-PSMA-1007 PET/CT for primary and metastatic lesions. [<sup>99m</sup>Tc]Tc-HFaPSMA showed excellent targeting specificity for both PSMA and FAP. It has the potential to overcome diagnostic limitations due to PSMA heterogeneity and is expected to advance its application in radioligand therapy.</p>","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"68 16","pages":"17598–17610"},"PeriodicalIF":6.8000,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Novel PSMA/FAP-Specific Radiotracer 99mTc-HFaPSMA for Diagnosis of PSMA-Negative Prostate Cancer: From Preclinical Validation to Clinical Translation\",\"authors\":\"Yuchen Wang, Xinru Li, Chenzhen Li, Huiyuan Xing, Rui Gao and Bing Jia*, \",\"doi\":\"10.1021/acs.jmedchem.5c01294\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >In this study, we reported a bispecific radiotracer [<sup>99m</sup>Tc]Tc-HFaPSMA to improve the diagnostic sensitivity of prostate cancer (PCa). [<sup>99m</sup>Tc]Tc-HFaPSMA was prepared by <sup>99m</sup>Tc radiolabeling of a HYNIC-conjugated bispecific biomolecule HFaPSMA, which combines a PSMA-targeting motif (PhPSMA), a FAP-targeting ligand (GFAPI), a symmetric PEG<sub>4</sub>-N-bis(PEG<sub>4</sub>-acid) linker, and a chelator (HYNIC). Preclinical studies showed faster clearance and higher tumor uptake than that of its corresponding single-target radiotracers ([<sup>99m</sup>Tc]Tc-HPSMA and [<sup>99m</sup>Tc]Tc-HGFAPI). Clinical SPECT/CT matched the resolution of [<sup>18</sup>F]FDG and [<sup>18</sup>F]F-PSMA-1007 PET/CT for primary and metastatic lesions. [<sup>99m</sup>Tc]Tc-HFaPSMA showed excellent targeting specificity for both PSMA and FAP. It has the potential to overcome diagnostic limitations due to PSMA heterogeneity and is expected to advance its application in radioligand therapy.</p>\",\"PeriodicalId\":46,\"journal\":{\"name\":\"Journal of Medicinal Chemistry\",\"volume\":\"68 16\",\"pages\":\"17598–17610\"},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2025-08-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Medicinal Chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.jmedchem.5c01294\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.jmedchem.5c01294","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
A Novel PSMA/FAP-Specific Radiotracer 99mTc-HFaPSMA for Diagnosis of PSMA-Negative Prostate Cancer: From Preclinical Validation to Clinical Translation
In this study, we reported a bispecific radiotracer [99mTc]Tc-HFaPSMA to improve the diagnostic sensitivity of prostate cancer (PCa). [99mTc]Tc-HFaPSMA was prepared by 99mTc radiolabeling of a HYNIC-conjugated bispecific biomolecule HFaPSMA, which combines a PSMA-targeting motif (PhPSMA), a FAP-targeting ligand (GFAPI), a symmetric PEG4-N-bis(PEG4-acid) linker, and a chelator (HYNIC). Preclinical studies showed faster clearance and higher tumor uptake than that of its corresponding single-target radiotracers ([99mTc]Tc-HPSMA and [99mTc]Tc-HGFAPI). Clinical SPECT/CT matched the resolution of [18F]FDG and [18F]F-PSMA-1007 PET/CT for primary and metastatic lesions. [99mTc]Tc-HFaPSMA showed excellent targeting specificity for both PSMA and FAP. It has the potential to overcome diagnostic limitations due to PSMA heterogeneity and is expected to advance its application in radioligand therapy.
期刊介绍：
The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents.
The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.
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