A Novel PSMA/FAP-Specific Radiotracer <sup>99m</sup>Tc-HFaPSMA for Diagnosis of PSMA-Negative Prostate Cancer: From Preclinical Validation to Clinical Translation
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.
Authors
- Hucheng Xing (ORCID: https://orcid.org/0000-0002-7738-3252)
- Chenzhen Li
- Bing Jia (ORCID: https://orcid.org/0000-0001-9346-1217)
- Xinru Li (ORCID: https://orcid.org/0000-0003-4846-9193)
- Rui Gao (ORCID: https://orcid.org/0000-0001-9835-1826)
- Yuchen Wang (ORCID: https://orcid.org/0000-0002-4006-7256)
Institutions
- Peking University (CN)
- First Affiliated Hospital of Xi'an Jiaotong University (CN)
- Office of Basic Energy Sciences (US)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2025-08-09
- DOI
- https://doi.org/10.1021/acs.jmedchem.5c01294
- Primary Topic
- Peptidase Inhibition and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China