A PSMA-targeted theranostic agent for photodynamic therapy

Area of Science:

• Oncology
• Medical Imaging
• Photodynamic Therapy

Background:

• Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and tumor neovasculature.
• PSMA is a validated target for cancer diagnostics and therapeutics.
• Developing targeted agents for imaging and therapy remains a critical need.

Purpose of the Study:

• To develop and evaluate a novel low-molecular-weight theranostic photosensitizer, YC-9, for PSMA-targeted optical imaging and photodynamic therapy (PDT).
• To assess the efficacy and safety of YC-9 in preclinical models of PSMA-expressing tumors.

Main Methods:

• YC-9 was synthesized by conjugating IRDye700DX to a PSMA-targeting moiety.
• In vivo optical imaging was used to evaluate tumor uptake and biodistribution.
• In vitro and in vivo photodynamic therapy (PDT) experiments were conducted in PSMA-positive and negative cancer models.

Main Results:

• YC-9 demonstrated specific uptake in PSMA-expressing tumors with rapid clearance from non-target tissues.
• In vitro studies confirmed YC-9-mediated, PSMA-specific cancer cell killing via PDT.
• In vivo PDT with YC-9 significantly delayed tumor growth and increased median survival in mice bearing PSMA+ tumors, with no observed toxicity.

Conclusions:

• YC-9 is a potent theranostic agent for PSMA-targeted photodynamic therapy (PDT).
• This agent shows potential for treating prostate tumors and other PSMA-expressing solid tumors.
• YC-9 offers a promising new strategy for targeted cancer therapy and imaging.