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Verena, Arsyangela; Merkens, Helen; Chen, Chao-Cheng; Chapple, Devon E.; Wang, Lei; Bendre, Shreya; Wong, Antonio A. W. L.; Bénard, François; Lin, Kuo-Shyan

Multidisciplinary Digital Publishing Institute

Some bispecific radiotracers have been developed to overcome the limitations of monospecific tracers and improve detection sensitivity for heterogeneous tumor lesions. Here, we aim to synthesize two bispecific tracers targeting prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP), which are key markers expressed in prostate cancer. A pyridine-based FAP-targeted ligand was synthesized through multi-step organic synthesis and then connected to the 2-Nal-containing PSMA-targeted motif. The K_i(PSMA) values of Ga-complexed bispecific ligands, Ga-AV01084 and Ga-AV01088, were 11.6 ± 3.25 and 28.7 ± 6.05 nM, respectively, and the IC₅₀(FAP) values of Ga-AV01084 and Ga-AV01088 were 10.9 ± 0.67 and 16.7 ± 1.53 nM, respectively. Both [⁶⁸Ga]Ga-AV01084 and [⁶⁸Ga]Ga-AV01088 enabled the visualization of PSMA-expressing LNCaP tumor xenografts and FAP-expressing HEK293T:hFAP tumor xenografts in PET images acquired at 1 h post-injection. However, the tumor uptake values from the bispecific tracers were still lower than those obtained from the monospecific tracers, PSMA-targeted [⁶⁸Ga]Ga-PSMA-617 and FAP-targeted [⁶⁸Ga]Ga-AV02070. Further investigations are needed to optimize the selection of linkers and targeted pharmacophores to improve the tumor uptake of bispecific PSMA/FAP tracers for prostate cancer imaging.

Article

eng

Vancouver : University of British Columbia Library

10.14288/1.0440670

Medicine, Faculty of; Radiology, Department of

10.3390/molecules29040800

Faculty; Researcher

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