Drug discovery and drug development are increasingly being accelerated by rapid synthesis of potential drugs and development of high-throughput in vitro tests. Imaging can play a major role in drug development because of its ability to quantify properties of the drug in vivo. Radionuclide imaging has been used in all phases of drug discovery and drug development, but pre-clinical studies could be the most effective application of imaging because the pre-clinical drug discovery process may be the slowest step. Piwnica-Worms and Marion have shown that knockout mice can be used to screen a number of potential candidates for clinical efficacy. The value of using these mice was also demonstrated for a series of potential muscarinic agonists using knockout mice with each of the five subtypes knocked out. These studies clearly showed that FP-TZTP was an M2 subtype-specific radioligand with appropriate pharmacokinetics in a minimal number of experiments. Further, the extrapolation from mice to humans was shown to be justified because the metabolic profile was similar, as shown by metabolism experiments with hepatocytes and in vivo studies in mice and rats. Thus knockout mice can be used to validate the radiolabelled drug in terms of specificity, saturability and pharmaco-kinetics, and liquid chromatography and mass spec-trometry can predict whether the metabolism data obtained in mice can be extrapolated to humans.

It is clear that PET imaging can be a major force in drug development.

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