Hybrid Tracers Based on Cyanine Backbones Targeting Prostate-Specific Membrane Antigen: Tuning Pharmacokinetic Properties and Exploring Dye-Protein Interaction.

Prostate cancer surgery is currently being revolutionized by the use of prostate-specific membrane antigen (PSMA)-targeted radiotracers, for example, Tc-labeled PSMA tracer analogs for radioguided surgery. The purpose of this study was to develop a second-generation Tc-labeled PSMA-targeted tracer incorporating a fluorescent dye. Several PSMA-targeted hybrid tracers were synthesized: glutamic acid-urea-lysine (EuK)-Cy5-mas, EuK-(SO)Cy5-mas, EuK-Cy5(SO)-mas, EuK-(Ar)Cy5-mas, and EuK-Cy5(Ar)-mas; the Cy5 dye acts as a functional backbone between the EuK targeting vector and the 2-mercaptoacetyl-seryl-seryl-seryl (mas) chelate to study the dye's interaction with PSMA's amphipathic entrance funnel.

Click Chemistry in the Design and Production of Hybrid Tracers.

Hybrid tracers containing both fluorescent and radioactive imaging labels have demonstrated clinical potential during sentinel lymph node procedures. To combine these two labels on a single targeting vector that allows tumor-targeted imaging, end-labeling strategies are often applied. For αβ-integrin-targeting hybrid tracers, providing an excellent model for evaluating tracer development strategies, end-labeling-based synthesis provides a rather cumbersome synthesis strategy.