Radiopharmaceutical Therapy

Our second patented product, Astatine-211-Parthanatine ([²¹¹At]PTT), is an alpha-emitting radiotherapeutic which uses our small molecule PARPi platform to deliver a cytotoxic radioactive charge directly to the PARP-1 tumor cell nucleus, killing the cancer cell by creating lethal, double stranded DNA breaks. The advantage of alpha particles compared to beta particles is that alpha particles are made of two protons and 2 neutrons, and emit radiation from 1 to 3 cell lengths, allowing for powerful and targeted tumor irradiation to the tumor cell nucleus.  Beta particles, which consist of one electron, can travel up for much larger distances, resulting in less targeted and less powerful radiation delivery, resulting in single stranded DNA breaks. Astatine-211 is a halide alpha emitter, ideal for small-molecule emitting radiopharmaceuticals that does not change the behavior of the underlying molecular platform.

Other alpha-emitting agents in current trials use elements such as actinium that significantly alter behavior resulting in poor molecular targeting.  [²¹¹At]PTT, a small molecule PARPi analog can be delivered quickly and effectively via the blood stream to cancer cancer cells, where it binds to the nucleus, optimizes the effectiveness of alpha emission for killing the cancer cell.  Unlike standard PARPi drugs, [²¹¹At]PTT requires only PARP-1 expression and binding, but not pharmacologic PARP inhibition, since alpha-radiation deposited by [²¹¹At]PTT is lethal when bound to a DNA-localized target like PARP-1. Therefore, [²¹¹At]PTT provides unparalleled potency for cancer therapy. [²¹¹At]PTT is in the pre-clinical stage with plans for Phase 1 trials in a number of different disease sites, including neuroblastoma and glioblastoma.