Home » Organometallics: A platform for molecular imaging probes. by Christopher Cain Caires
Organometallics: A platform for molecular imaging probes. Christopher Cain Caires

Organometallics: A platform for molecular imaging probes.

Christopher Cain Caires

Published
ISBN : 9781109076608
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354 pages
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 About the Book 

Molecular imaging is a powerful technique that is driving the future of diagnostic medicine. The ability to be able to measure molecular concentrations and events, including the presence of specific cellular proteins and gene expression in livingMoreMolecular imaging is a powerful technique that is driving the future of diagnostic medicine. The ability to be able to measure molecular concentrations and events, including the presence of specific cellular proteins and gene expression in living subjects, is a powerful tool that can be used to understand, diagnose, and treat a diverse array of pathology. Positron Emission Tomography, or PET imaging, is a critical component of molecular imaging since its pM sensitivity and unlimited depth of penetration gives us the best way of imaging molecules in humans.-The design and synthesis of new PET imaging probes is a significant bottleneck driven largely by a dearth of trained radiochemists. The consequence is that innovation and discovery are stifled since the limited personnel resources cannot nearly accommodate the requests from the research community to assist in investigating new PET imaging probes.-My work is focused on unclogging this bottleneck and developing radiochemical methods that obviate the need for trained radiochemists. The strategy employed is a wash-in approach where [18F-] is covalently attached to a molecular probe directly from the aqueous solution obtained from the cyclotron target. This method avoids the costly steps and technical expertise that is typically required to convert [18F -] into a useable molecular probe.-We investigated a wash-in approach using organobismuth and antimony conjugates that would form the inorganic E -- 18F bond in water. We found that we could form E -- 18F bonds in water and that the bond was stable in the presence of low quantities of other competing anions. However, the stability required for in vivo applications is rigorous and our complexes did not perform as required. A redesign of the complexes introduced multiple sites of coordination using boron, silicon, and hydrogen bonds, but did not perform as expected and instead fragmented to benzyne products.-Our final strategy involved using silver to promote C -- 18F bond formation in water and here we found success. A simple model showed we could achieve 47% radiochemical yield in 45 min. at 25 °C.-We envision that with proper optimization our aqueous labeling method will open up PET imaging probe development to a wider research community and foster innovation and growth in this increasingly important tool for studying disease.