PSMA and Integrin αvβ3 Dual-Targeted Radioligands for Prostate Cancer Targeted Radionuclide Therapy

Area of Science:

• Nuclear medicine
• Oncology
• Radiopharmaceutical chemistry

Background:

• Metastatic castration-resistant prostate cancer (mCRPC) poses significant treatment challenges due to tumor heterogeneity.
• Single-target radiopharmaceuticals have limitations, including variable antigen expression, necessitating novel therapeutic strategies.

Purpose of the Study:

• To develop and evaluate a novel dual-targeting radioligand for prostate cancer.
• To assess the efficacy and safety of the dual-targeting radioligand in preclinical models.

Main Methods:

• Solid-phase synthesis and click chemistry were used to create the dual-targeting radioligand ¹⁷⁷Lu-PSMA-3-RGD.
• The ligand was designed to bind both prostate-specific membrane antigen (PSMA) and integrin α_vβ₃.
• In vitro and in vivo studies were conducted using PSMA-positive cells and xenograft models.

Main Results:

• The radioligand demonstrated high radiochemical purity and stability, with selective uptake in PSMA-positive cells.
• In vivo studies showed rapid tumor accumulation, prolonged retention, and specificity.
• Therapeutic administration led to significant tumor growth delay compared to single-targeted agents without systemic toxicity.

Conclusions:

• The dual-targeting radioligand ¹⁷⁷Lu-PSMA-3-RGD is a highly effective theranostic candidate for prostate cancer.
• This approach overcomes limitations of single-target therapies.
• Further preclinical and clinical investigations are warranted.