PRECLINICAL DEVELOPMENT OF ALPHA-PARTICLE THERAPEUTICS

Internal radiation therapy is an alternative method to external beam radiation therapy for the treatment of cancer. Alpha (α)-particle based internal radiation therapy methods are being explored to improve the efficacy and toxicity compared to using beta (β-)-emitting isotopes. Two α-particle delivery platforms were developed; Pb-212-GlaS-Fc, which utilizes a systemic targeted approach, and Bi-212-MAA, which is a short-lived locoregionally delivered embolic radiopharmaceutical. Both of these radiopharmaceuticals were shown to be efficacious in treatment of cancer cells and be potential clinic therapeutics. Further, Bi-212-MAA was used as a platform to understand cellular and molecular responses of cancer to α-particle radiation. It was found that cancer cells are unable to utilize certain canonical radiation resistant responses, such as cell cycle control, when treated with α-particles. Additionally, cytokine production was dysregulated in these cells after treatment. These findings indicate that these two new delivery strategies have potential for translation to the clinic and that Bi-212-MAA can be used as a tool to elucidate additional molecular effects of α-particles on cancer cells.