Optimizing [²¹²Pb]Pb-AB001 Radiopharmaceutical Therapy Schedules in PSMA-Positive Subcutaneous Prostate Cancer...

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Therapy
• Oncology

Background:

• Prostate-specific membrane antigen (PSMA)-targeted radioligands like [212Pb]Pb-AB001 show promise for metastatic prostate cancer.
• Optimizing administration schedules is crucial for maximizing therapeutic benefits and minimizing toxicity in radiopharmaceutical therapies.

Purpose of the Study:

• To evaluate the impact of different treatment schedules and cumulative activities of [212Pb]Pb-AB001 on therapeutic efficacy and toxicity in a preclinical prostate cancer model.
• To determine the optimal dosing regimen for [212Pb]Pb-AB001 therapy.

Main Methods:

• Male athymic nude mice with PC-3 PIP xenografts received [212Pb]Pb-AB001 at various cumulative activities (0.8-1.6 MBq) and schedules (single, Q7d, Q14d, Q3d).
• [18F]PSMA-1007 PET/CT imaging assessed radioligand uptake. Tumor growth, survival, toxicity, and histopathology were analyzed.

Main Results:

• All [212Pb]Pb-AB001 regimens delayed tumor growth and prolonged survival compared to controls.
• The Q7d regimen demonstrated superior tumor control over Q14d and Q3d schedules.
• Increasing cycles and per-cycle activity (e.g., 4x0.4 MBq Q7d) significantly improved median survival to 116 days with 33% complete responses.
• Repeated treatment led to tumor necrosis and reduced PSMA/VEGF staining without systemic toxicity.

Conclusions:

• Therapeutic efficacy of [212Pb]Pb-AB001 is dependent on cycle number, interval, and per-cycle activity.
• Multicycle administration enhances tumor control and survival without observed toxicity.
• These findings support the optimization of [212Pb]Pb-PSMA therapy schedules in clinical settings.