Treating Alzheimer's Disease with Targeted Alpha Therapy

Targeted alpha therapy has gained recognition for the treatment of cancers. The therapeutic efficacy of alpha particles lies in the short range and high linear energy transfer of these ionizing particles. Alpha particles emitted in decay have energies ranging from 4-9 MeV, yet travel micrometer distances through tissues breaking chemical bonds as a result of energy lost to the surrounding tissue. We propose that a similar strategy can be used for the treatment of Alzheimer’s disease.
Using an analog of [F-18]-flutemetamol , an FDA approved drug for Positron Emission Tomography (PET) imaging of Alzheimer’s patients, we propose the attachment of At-211, in lieu of F-18. At-211, a radiohalogen, exhibits a 7-hour half-life and decays via the emission of an alpha particle. We have chemically synthesized sufficient quantities (>50 mg) of a boronic acid precursor and are prepared to generate the astatinated compound.
This project combines the expertise of faculty from the Colleges of Engineering, Science, and the School of Medicine to address the societal problem of Alzheimer’s disease. These distinct backgrounds are needed to help address this problem and will encourage partnerships throughout the university. This project will cultivate new collaborations that would result in the innovation, education and multidisciplinary training of young researchers. If funded, follow-on funding would likely be obtained through the NIH, aiding the long-term viability of the collaboration.

Current Status

2021-09-14
Abstract:
Targeted alpha therapy has gained recognition for the treatment of cancers. The therapeutic efficacy of alpha particles lies in the short range and high linear energy transfer of these ionizing particles. Alpha particles, emitted during decay, deposit several MeV of energy in micrometer distances through tissues; breaking chemical bonds due to energy lost to the surrounding tissue. We proposed that a similar strategy can be used for the treatment of Alzheimer’s disease (AD) using the alpha particles energy to breakup AD plaques and reduce disease burden.We synthesized anAt-211analog of [F-18]-flutemetamol, an FDA approved drug for Positron Emission Tomography (PET) imaging of Alzheimer’s patients,developinga therapeutic agentfor use in targeted alpha therapy of AD. At-211exhibits a 7-hour half-life and decays via the emission of an alpha particle. We successfully radiolabeled our compound with At-211 with the help of our collaborators at the University of Washington. Furthermore, we enhanced our laboratories capabilities to includeELISA and staining of mouse tissues affected with ADtoquantify the plaque load before and after treatment. This work will result in one publication and has been used as preliminary data in NIH and DOE grant applications.