Cyclooxygenase 2 (COX-2) as a target for therapy and noninvasive imaging.

Abstract Prostaglandins modulate a wide range of biologic functions, including wound healing, temperature regulation, reproduction, and many aspects of immune function. Exaggerated production of prostaglandins contributes to a large number pathophysiologies. The critical enzyme in prostaglandin biosynthesis is prostaglandin synthase, also known as cyclooxygenase (COX). The nonsteroidal anti-inflammatory drugs (NSAIDs), one of the largest classes of pharmaceutical agents, exert most of their biologic effects by inhibiting cyclooxygenase production of prostaglandins. The discovery of a second, inducible form of cyclooxygenase, now known as COX-2, responsible for the production of prostaglandins in most pathological states, revived a relatively moribund research area in biochemistry, physiology, and pharmacology, and led to the search for and discovery of a new class of pharmacologic agents. The coxibs have greater efficacy and substantially ameliorated side effects when compared to the classic NSAIDs. Because of the pervasive role of COX-2 in a wide range of human pathologies, the coxibs have been the most successful entry into the pharmaceutical market in history, responsible for $6–10 billion in sales annually. The ability to noninvasively monitor COX-2 expression with molecular imaging probes will provide a corresponding advance in diagnosing COX-2-based disease, monitoring progression of such diseases, and evaluating alternative therapies.