Novel 11C-Methylation Strategies and Their Application in CNS Receptor Imaging

Student thesis: Doctoral ThesisDoctor of Philosophy


Positron emission tomography (PET) is a non-invasive molecular imaging technique that provides quantitative and qualitative data on the biodistribution of radiolabelled molecules in vivo. Among the positron (β+) emitting radionuclides used in PET radiopharmaceutical production, carbon-11 (11C, radioactive half-life = 20.4 min) is a valuable choice due to the ubiquity of carbon atoms into biologically-active organic molecules and the preservation of biological characteristics upon isotopic substitution of carbon-12. Cyclotron products of 11C is usually obtained as [11C]CO2, which presents limited reactivity and often requires conversion into more reactive labelling agents (e.g. [11C]CH3I) via time-consuming processes that contrast with the short half-life of 11C. The development of novel strategies to enhance the reactivity of [11C]CO2 would avoid the need of synthon conversion steps and would shorten the total processing time for radiopharmaceutical production.

This thesis discusses the development of a novel methodology for 11C-formylation from [11C]CO2. In spite of the wide chemical reactivity and presence in biologically-active molecules, the 11C-labelling on the formyl group has not yet been developed, limiting the access to this important class of compounds.

The thesis will also discuss the development of a novel methodology for 11C-methoxylation from [11C]CO2. This methodology utilises organosilyl reagents and compared to current O-11C-methylation procedures with [11C]CH3I does not require time-consuming synthon conversion steps or synthon-dedicated synthesis units.

The application of these methodologies will expand the pool of molecules available for radiolabelling and the number of applications in PET imaging.
Date of Award1 Jun 2022
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorTony Gee (Supervisor), Salvatore Bongarzone (Supervisor) & Philip Blower (Supervisor)

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