Grant: Discovery Grants Program - Individual

Finding imaging agents to diagnose and study health and disease is as challenging as drug discovery and often needs synthesis of dozens of candidates and complex testing methods in cells and animals, all of which may fail. It is also limited by methods to precisely attach radioactive isotopes to molecules and typically needs a unique, activated precursor for each new candidate. Our research lab is a leader in discovering methods for making new molecules with carbon-11 carbon dioxide by linking stable precursors together while labeling. These innovations make a different strategy for tracer discovery attractive. We connect easy radiolabeling with fast experiments to find key properties for a given tracer application, speeding up the entire process. This Discovery Program will improve radiotracer development and build new chemical reactions with carbon dioxide. Radiotracer discovery: Imaging agents for a target often share a common structure with minor differences. For example, many tracers targeting prostate cancer have a common urea that leads to relatively low levels of entering cells. We will use our chemical methods to make many changes to the urea to find examples that enter cells more and do not lead to kidney damage, based on fast and simple cell assays and imaging. We are also going to find imaging agents for studying dopamine receptors in the brain by mixing and matching parts of new drugs that we believe will provide a cleaner picture. Dopamine imaging is needed to understand cognition, fear, depression, and psychiatric diseases. Carbon-11 chemistry: The chemical methods we discover using reactive atoms, catalysts, and light to make radioactive molecules from carbon dioxide give us the tools to make new imaging agents. We need to continue to build better tools for researchers and hospitals around the world. We will focus on better catalysts and ways to use light in synthesis. We will also study ways to keep more carbon dioxide in solution and make it more reactive so that the methods we already have work better. This is important so that tracer manufacturing can serve more people and make carbon-11, already one of the safest imaging isotopes, more practical to use. Lastly, we believe that these catalysts can help us work with forms of carbon-11 that have been difficult to study, including formaldehyde and methanol. These fundamental studies have real applications for imaging and could also teach us about chemistry that can be applied for other purposes. Carbon-11 is used in hospitals and is unique in its potential to label practically all drugs and biomolecules. With more sensitive imaging systems, carbon-11's short half-life (20.4 min) will not be a limitation for practical applications, but rather an advantage for its safety. We need to train chemists to work with this isotope and support growing commercial and healthcare demands for better technologies and experts in imaging chemistry.