Project Summary / Abstract Targeted alpha therapy is an emerging technique for treating cancer showing great promise to deliver a precise and potent cell-killing treatment to multiple cancer varieties. The design of these targeted radiopharmaceuticals combines a tumor- selective carrier molecule bound to an alpha-particle-emitting radionuclide. The carrier molecule selectively binds to the intended cancer cells, and the limited lethal spatial range of alpha particles emitted by the attached radionuclide yields a targeted therapeutic effect by destruction of the cancer cells. Researchers are designing a variety of carrier molecules and experimenting with radionuclide isotopes to get the best therapeutic effect. The novelty of the field means that tools are still lacking to help researchers and other medical innovators to (1) characterize the spatial distribution of the therapeutic resulting from carrier molecule design and (2) fully understand the fate of their chosen isotopes which chain-wise decay into progeny isotopes which may have different affinities, toxicities, and effects. Our goal in this grant is to develop an innovative, quantitative radiation imaging tool that allows researchers and radiopharmaceutical developers to not only see the spatial distribution of targeted alpha therapy molecules at a near-cellular level, but to also see the emitting molecules labeled by their emitting isotope, effecting a form of isotopic spectroscopy. This work builds upon our previous research in which we demonstrated a non-optimized but innovative algorithm for labeling parent and progeny isotopes. We now aim to refine this algorithm to achieve real-time isotopic spectroscopy, combine it with a highly optimized hardware design for isotopic imaging, and bring the combined result to market. This device will be an extremely useful tool for radiopharmaceutical experts, producing quantitative, quality-assured results to support their development of the next great cancer treatments. We believe this project brings together our expertise in image science, real-time algorithm design, and product development to produce an invaluable tool for researchers working in this most-promising area of cancer therapy research.

Project Narrative: Targeted alpha therapy is a promising approach to precise targeting and elimination of smaller cancers which has already found success in FDA-approved treatments for bone metastases from prostate cancer. This project develops a technology for imaging the distribution of alpha and beta emitters and then assigning labels to the various primary and decay isotopes of the emitter, resulting in a form of spectroscopy. The technology developed by this project will result in a powerful tool for radiopharmaceutical researchers to characterize the distribution and fate of various radioactive isotopes for their candidate targeted alpha therapy molecules at various stages of study as notably this ability is currently not available.