Imaging hastens drug discovery and development
In drug discovery and development, single-photon-emission CT and PET can be used for monitoring the drug, the drug target or the physiological processes. MRI and CT can provide an anatomical backdrop for the area that is radiolabeled for these imaging modalities, and all of these techniques notably can be transferred from animal to human studies.
In a review, Richard J. Hargreaves, vice president of imaging at Merck Research Laboratories in West Point, Pa., asserts that PET has proved to be the most useful of these molecular imaging modalities so far, especially for oncology and neuroscience drug investigations. For example, the widely used tracer metabolized by glycolysis, [18F]fluorodeoxyglucose, is used routinely to follow tumor growth and metastasis. Other tracers that report on tumor physiology based on the 18F heavy isotope are being investigated for cell proliferation, angiogenesis and apoptosis.
Hargreaves provides several examples of the effective use of PET in the neurosciences. Using the technique, his team discovered early that a proposed obesity drug did not cause clinically significant weight loss despite full target engagement in the brain, and the group also successfully used the method to characterize cannibinoid-1 receptor distribution in the brain. It has been using microarray analysis to identify new targets for molecular tracers to characterize atherosclerotic plaque.
The challenges of molecular imaging, Hargreaves notes, are that validating new tracers can be time-consuming and often lacks rigorous standardization across all treatment centers in multicenter clinical trials. The costs of qualifying an imaging marker as a surrogate for an outcome in a clinical trial can be equivalent to developing a drug. However, this burden can be reduced greatly by working in consortia with academic, government and advocacy groups.
Hargreaves concludes that molecular imaging methods can identify promising drug candidates or ineffective compounds early, saving time and money. Therefore, molecular imaging has become increasingly important for drug discovery and development. (Clinical Pharmacology & Therapeutics, February 2008, pp. 349-353.)
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