Bimodal Fluorescent Conjugate Based on Prostate-Specific Membrane Antigen Ligands with the Chelating Agent DOTA and SulfoCy5 Dye: Synthesis, Radiolabeling, and Biological Activity.

Prostate-specific membrane antigen (PSMA) is an essential zinc-dependent metalloprotease classified within the type II transmembrane protein family, often referred to as glutamate carboxypeptidase II (GCPII). PSMA is recognized as a particularly promising target for both the diagnosis and therapeutic intervention of prostate cancer. In this study, we designed and synthesized PSMA-targeted DOTA-loaded bimodal conjugate 11 with SulfoCy5 fluorescent dye, performed in vitro characterization, and analyzed biodistribution in vivo. At 40-100 nM concentrations, the resulting conjugate demonstrated reliable visualization of tumor cells, on par with the reference PSMA-SylfoCy5 compound. In vivo biodistribution analysis of [68Ga]Ga-11 in mice demonstrated a reduction in renal accumulation in comparison with dye-free conjugate [68Ga]Ga-10. The specificity of [68Ga]Ga-11 for PSMA was confirmed in a murine LNCaP xenograft model: its effective accumulation in tumors and kidneys, as well as relatively rapid elimination from non-target tissues, make it a promising agent for PET imaging but not radionuclide therapy.