PET Radiotracer development based on existing ATM-inhibitors
Awardee: Jacob Hooker
Institution: Massachusetts General Hospital
Grant Amount: $116,172.00
Funding Period: February 1, 2023 - January 31, 2024
Summary:
Ataxia-telangiectasia (A-T) is a rare autosomal recessive genetic disease that involves progressive neurodegeneration (cerebellar atrophy), immune deficiency, lung problems and a strikingly high increased risk of cancer. Children with A-T start life with almost normal motor function but then lose muscle control and balance so that speech, eye-tracking and swallowing become much more difficult, and they usually need to use wheelchairs by age nine. Multiple therapeutic strategies are being pursued clinically but there is no direct functional restoration measure of ATM, the PIKK (PI3K-like protein kinase) available for therapeutic monitoring in the brain. Our hypothesis is that functional ATM presents a binding site for a small-molecule-based ATM-inhibitor and thus binding of the inhibitor can be used as a proxy measure of the functional concentration of ATM. By labeling ATM-inhibitors with a positron emitting isotope, it thus may be possible to image the amount of functional ATM in the brain using positron emission tomography. We will synthesize and radiolabel a series of ATM-inhibitors for evaluation of this functional biomarker concept.