Theranostic Targeting of Cyclooxygenase-2: The Why, How and When?

Dear Colleagues,

COX-2, the inducible isoform of cyclooxygenases or prostaglandin-endoperoxide synthases (EC 1.14.99.1), is a key player in inflammatory, regenerative, and tumor-associated processes. The fact that this enzyme is only basally expressed and synthesized in a few organs and tissues in the healthy state, but is induced and highly activated in a tissue inflammatory response, makes it a highly attractive target for diagnostic and therapeutic approaches.

From the diagnostic side, non-invasive imaging and quantification of the functional expression of this enzyme as an indicator of an acute or chronic inflammatory response is highly desirable. However, COX-2 is a very challenging molecular target due to its localization within the cell and its lipophilic substrate and inhibitor-binding pocket. After all, a tracer, whether radionuclide- or dye-labeled, must penetrate two membranes in suitable quantities and with a suitable time window in order to reach the enzyme. This requires both sufficient lipophilicity as well as selectivity regarding the concomitant inhibition of COX-1 in addition to the maintenance of specificity. Despite extensive efforts, no suitable tracer approach has yet found its way into the clinic.

This Special Issue therefore invites all groups committed to the development of COX-2-targeting tracer and imaging approaches in order to present novel research involved in visualizing this enzyme, either in vitro or in vivo, as well as pharmacokinetic studies providing leads for radionuclide-based imaging rather than classical therapeutic interventions. In addition, we hope to stimulate an open, critical, and sound debate about the chances but also woes and sorrows, or even the pros and cons, of COX-2 as an imaging target.

There is no doubt that knowledge of the functional expression of this enzyme during the course of a disease, during therapy, and in the healing process will allow important differential diagnostic and therapeutic conclusions to be drawn. Experience in recent years with anti-inflammatory treatment selectively directed against COX-2 by selective COX-2 inhibitors, also named coxibs, has shown that mere inhibition of the enzyme is not always indicated. It is often important to modulate the activity of COX-2 to the right extent and in the right time window. The short-term use of selective COX-2 inhibitors can certainly be considered a success story with respect to less gastric irritation and decreased risk of peptic ulceration compared to non-selective inhibitors. Increasingly, combined/adjuvant approaches are also discussed, for example, to support tissue regeneration, radiosensitize tumors, or in the radioprotection of normal tissue. Long-term treatment, on the other hand, can disturb the balance in prostanoid metabolism and, thus, is often accompanied by serious side effects, particularly, affecting the vascular system.

This Special Issue therefore also aims to provide a forum for contributions that present or critically examine current developments and possibilities for application of selective COX-2 inhibitors, and then enter into an inspiring discussion on new therapeutic approaches, such as novel lead structures, dual inhibitors, adjuvant and combined therapeutic approaches, drug release aspects, and more.

This Special Issue is roughly divided into four chapters. The content of the individual submitted papers is assigned on the basis of the selected keywords, which can be found in the following list. 

Prof. Dr. Jens Pietzsch
Dr. Markus Laube
Guest Editors

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