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.