Texaphyrins: New drugs with diverse clinical applications in radiation and photodynamic therapy

Abstract

The texaphyrins are quintessential metal-coordinating expanded porphyrins. They constitute a new series of synthetic porphyrin analogues that show promise as drugs for use in a range of medical therapies. Currently, two different water-solubilized lanthanide(III) texaphyrin complexes, namely the gadolinium(III) and lutetium(III) derivatives 1 and 2 (Gd-Tex and Lu-Tex, respectively), are being tested clinically. The first of these, XCYTRIN™, is in a pivotal Phase III clinical trial as a potential enhancer of radiation therapy for patients with metastatic cancers to the brain receiving whole brain radiation therapy. The second, in various formulations, is being tested as a photosensitizer for use in: (i) the photodynamic treatment of recurrent breast cancer (LUTRIN™; Phase II clinical trials complete), (ii) photoangioplastic reduction of atherosclerosis involving peripheral arteries (ANTRIN™; now in Phase II testing), and (iii) light-based treatment of age-related macular degeneration (OPTRIN™; currently in Phase I clinical trials), a vision-threatening disease of the retina. Taken in concert, these two metallotexaphyrins provide a powerful new class of experimental drugs whose diverse potential utility is abetted by a combination of well-optimized physical features, favorable tissue biolocalization characteristics, and novel mechanisms of action. Interestingly, these mechanisms may alter conventional wisdom regarding mechanisms of radiation therapy and the pathophysiology of atherosclerosis.