1996 Hoffman–LaRoche Award Lecture Photochemistry and photobiology of perylenequinones

Photodynamic therapy relies on the selective accumulation of photosensitizers within neoplastic tissue, followed by light activation to generate cytotoxic singlet oxygen. At present, PhotofrinTM, a preparation of hematoporphyrin derivatives (HPD) with the bulk of the porphyrin monomers removed, is the only clinically approved photosensitizer. Intravesical administration of Photofrin or HPD has failed to photosensitize bladder tumors. Bladder cancer is the second most common genitourinary malignancy. In 1994 there were an estimated 51 200 cases of bladder cancer with 10 600 deaths in the United States. The predominant histopathology is transitional cell carcinoma, occurring in 90–95% of these cases. Most patients (85%) have superficial disease at the time of initial diagnosis. Superficial bladder cancer is defined as disease involving the mucosa with carcinoma in situ or papillary lesions and invasion limited to submucosa. To address these limitations we have been conducting preclinical studies with perylenequinones (PQs). The majority of our effort has focused on developing and characterizing derivatives of PQs. Following site-directed modifications, we have identified certain congeners that warrant further preclinical development. These compounds are monomeric and do not effect cutaneous photosensitization beyond 24 h. With clinically relevant drug and light doses we have cured >90% of experimental subcutaneous murine tumors. Keywords: photodynamic therapy, perylenequinones, photobiology, photochemistry.