Novel [⁶⁸Ga/¹⁷⁷Lu]Ga/Lu-AZ-093 as PSMA-Targeting Agent for Diagnosis and Radiotherapy

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Chemistry
• Oncology

Background:

• Prostate-specific membrane antigen (PSMA) is a key target for prostate cancer diagnosis and therapy.
• Existing PSMA-targeting agents like [⁶⁸Ga]Ga-P16-093 and [¹⁷⁷Lu]Lu-PSMA-617 have shown clinical utility.
• Development of novel chelators like AAZTA offers opportunities for improved theranostic agents.

Purpose of the Study:

• To evaluate AAZTA-Gly-O-(methylcarboxy)-Tyr-Phe-Lys-NH-CO-NH-Glu (AZ-093) as a PSMA-targeting agent.
• To establish a gallium-68/lutetium-177 theranostic pair ([⁶⁸Ga]Ga-AZ-093/[¹⁷⁷Lu]Lu-AZ-093) for prostate cancer.
• To assess the diagnostic and therapeutic potential of the developed theranostic pair.

Main Methods:

• Synthesis and characterization of the precursor AZ-093.
• Radiolabeling of AZ-093 with Gallium-68 ([⁶⁸Ga]) and Lutetium-177 ([¹⁷⁷Lu]).
• In vitro studies: binding affinity, cell uptake, and retention in PSMA-positive cells (22Rv1-FOLH1-oe).
• In vivo studies: tumor targeting, uptake, and retention in a mouse model with PSMA-positive tumors.

Main Results:

• AZ-093 was successfully synthesized and radiolabeled with [⁶⁸Ga]Ga and [¹⁷⁷Lu]Lu with high yields and purity.
• In vitro studies showed comparable PSMA-targeting properties to existing agents, with specific, time-dependent cellular uptake and internalization.
• In vivo studies demonstrated excellent tumor uptake and retention of both [⁶⁸Ga]Ga-AZ-093 and [¹⁷⁷Lu]Lu-AZ-093 in PSMA-positive tumors.

Conclusions:

• The [⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu-AZ-093 theranostic pair exhibits potent PSMA-targeting capabilities.
• AZ-093 is a promising candidate for developing novel PSMA-targeting agents for prostate cancer diagnosis and therapy.
• This theranostic pair holds potential for improved management of prostate cancer patients.