Preliminary Evaluation of Astatine-211-Labeled Bombesin Derivatives for Targeted Alpha Therapy

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Chemistry
• Oncology

Background:

• Bombesin (BBN) derivatives are used for prostate cancer diagnostics and therapeutics.
• Astatine-211 (211At)-labeled BBN derivatives have not been previously studied.
• Prostate cancer remains a significant health concern, necessitating novel therapeutic and diagnostic agents.

Purpose of the Study:

• To present a preliminary evaluation of a novel 211At-labeled BBN derivative for prostate cancer.
• To synthesize and characterize 211At-labeled BBN derivatives.
• To assess the in vitro and in vivo behavior of the developed radiotracer.

Main Methods:

• Synthesis of nonradioactive iodine-introduced BBN derivatives (IB-BBNs) with varying linkers.
• Radiolabeling of a selected BBN derivative with 211At to produce [211At]AB-3.
• Evaluation of radiochemical yield, purity, in vitro stability, and cell internalization/externalization.
• Biodistribution studies in PC-3 tumor-bearing mice with and without excess native BBN.

Main Results:

• IB-3 showed comparable binding affinity to native BBN.
• [211At]AB-3 was synthesized with a radiochemical yield of 28.2 ± 2.4% and purity >90%.
• The radiotracer was internalized by cells, but significant radioactivity efflux was observed over time.
• Despite poor plasma stability, [211At]AB-3 accumulated in PC-3 tumors (4.05 ± 0.73%ID/g), an effect inhibited by excess BBN.
• Organ accumulation was likely due to free 211At, suggesting deastatination.

Conclusions:

• [211At]AB-3 demonstrates potential for prostate cancer targeting, evidenced by tumor accumulation.
• Peptide degradation in plasma and radioactivity efflux from cells are key limitations.
• Future development necessitates BBN sequence modification and strategies to prevent deastatination for improved therapeutic efficacy.