Fluorescent PSMA-Targeted Radiotheranostic Compounds for Multiscale Imaging.

Area of Science:

• Biomedical imaging
• Radiopharmaceutical therapy
• Molecular imaging

Background:

• Prostate-specific membrane antigen (PSMA) is a key target for prostate cancer theranostics.
• Understanding the cellular distribution of PSMA-targeting agents is crucial for optimizing theranostic probe development.
• Current PSMA ligands lack detailed single-cell pharmacokinetic data.

Purpose of the Study:

• To synthesize and characterize fluorescent analogs of PSMA-targeting ligands.
• To enable detailed single-cell pharmacokinetic studies of PSMA-targeting agents.
• To guide the development of next-generation theranostic probes for prostate cancer.

Main Methods:

• Solid-phase synthesis of fluorescent PSMA analogs based on PSMA-617.
• Optimization of the urea pharmacophore synthesis.
• In vitro and in vivo evaluation of synthesized fluorescent ligands, including binding affinity and optical imaging properties.
• Tissue and cellular biodistribution analysis using fluorescence imaging.

Main Results:

• Two fluorescent PSMA ligands, PSMA-Lys-DOTA-Cy680 (3) and PSMA-Lys-DOTA-AF647 (4), were successfully synthesized.
• These compounds exhibit PSMA binding affinities comparable to the parent compound.
• The synthesized ligands demonstrate robust optical imaging properties and provide detailed biodistribution data.

Conclusions:

• Fluorescent PSMA ligands can provide valuable insights into cellular pharmacokinetics.
• This research facilitates microdosimetric and systemic modeling for improved radiopharmaceutical therapy design.
• The developed fluorescent probes represent a significant advancement in PSMA-targeted theranostics.