Imaging of cyclooxygenase-2 (COX-2) expression: potential use in diagnosis and drug evaluation.
Cyclooxygenase is an enzyme that catalyzes the first two steps in the biosynthesis of prostanoids. The constitutively expressed isoform COX-1 is regarded as a housekeeping enzyme that is responsible for the normal production of prostanoids. The inducible isoform COX-2, on the other hand, is transiently induced during inflammation by various stimuli. Increasing evidence has shown that COX-2 is not only implicated in inflammation but also in oncogenesis. Overexpression of COX-2 has been observed in a variety of tumors. Prostaglandins produced by COX-2 affect important processes in carcinogenesis, including angiogenesis, tissue invasion, metastasis and apoptosis. Several studies indicate that COX-2 is also involved in neurological disorders, like Alzheimer's disease, Parkinson's disease and ischemia, where COX-2 overexpression leads to neurotoxicity. Many aspects of the role of COX-2 in (patho)physiology, however, remain unclear. At present, COX-2 expression is determined by ex vivo laboratory analysis, but the results could be greatly affected by the instability of COX-2 mRNA and protein and by sampling errors. A noninvasive imaging method to monitor COX-2 expression, like positron emission tomography (PET) or single photon emission computed tomography (SPECT), could overcome this complication and may provide novel insights in the role of COX-2, especially in neurological disorders where repetitive sampling is not possible. Such a technique could also be applied to the in vivo evaluation of novel selective COX-2 inhibitors and in dose-escalation studies. This review will present an overview of the developments in the recently emerging field of COX-2 imaging.
de Vries
E F J
EF
Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. e.f.j.de.vries@pet.umcg.nl
D000818:Animals; D000829:Animals, Domestic; D051546:Cyclooxygenase 2 / Q000032:analysis* / Q000096:biosynthesis* / Q000502:physiology / Q000633:toxicity; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D015899:Tomography, Emission-Computed, Single-Photon
D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2