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| 2 Research Method Development 2.7 Radiometabolite analysis A radiotracer injected into a living subject will be exposed to the actions of metabolizing enzymes in the periphery and brain. The extent of radiotracer metabolism is usually very significant (> 50%) over the span of a PET experiment. Only very few radiotracers completely resist metabolism.50 With regard to deriving measures of target protein in brain (e.g. BP) from bio-mathematical models, it is important to know the degree to which radioactivity in brain tissues resides on parent radiotracer or its metabolites, and how this changes with time. The ideal is that only parent radiotracer is seen in brain. Confidence that radiometabolites do not contaminate the recorded PET signal is established by the characterization of in vivo metabolism in rodent and non-human primate by HPLC analysis of blood (plasma) and, also for rodent, brain tissue extracts. HPLC analysis of radiometabolites generated in human blood in vitro is also performed. LC-MS-MS is applied to obtain structural information on major radiometabolites. Specific examples51,52,53,54 of this approach are also mentioned in the Radiotracer Discovery & Development section. |
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