The Status of Pet Radiochemistry for Drug Development and Evaluation

Abstract

Positron emission tomography (PET), when coupled to appropriate organic radiotracers, is a powerful quantitative imaging technique for probing biochemical pathways, molecular interactions, pharmacokinetics, and pharmacodynamics in humans, including those of developmental drugs. The range of parameters that may be investigated is determined by the availability of effective radiotracers. Developmental drugs may be labeled with positron-emitters to obtain direct information on biodistribution, pharmacokinetics, or metabolism. Alternatively, reference radiotracers for blood flow, metabolism, and receptor or enzyme distribution may be used to assess drug pharmacodynamics and binding site interactions.

Each radiotracer must be labeled appropriately with a positron-emitter. Consequently, radiochemical science is a key area for expanding the power of PET for clinical, biochemical, and pharmacological investigations. The most useful positron-emitters, namely carbon-11 and fluorine-18, have short half-lives measured in minutes. Hence, the need to label organic molecules rapidly, efficiently, and regularly for human administration, often at a very high specific radioactivity, is a very special challenge. Here the status of PET radiochemistry is described with special emphasis on recent advances and the potential for application in drug development and evaluation.