Author:

Keywords:

Animals, Antineoplastic Agents, Carcinoma, Transitional Cell, Female, Injections, Intraperitoneal, Neoplasm Recurrence, Local, Neoplasms, Experimental, Perylene, Photochemotherapy, Radiation-Sensitizing Agents, Rats, Rats, Inbred F344, Tissue Distribution, Treatment Outcome, Tumor Cells, Cultured, Urinary Bladder Neoplasms, Science & Technology, Life Sciences & Biomedicine, Oncology, hypericin, transitional cell carcinoma, photodynamic therapy, RAT BLADDER, THERAPY, LIGHT, PHOTOSENSITIZATION, DESTRUCTION, LEAKAGE, OXYGEN, SITU, Anthracenes, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, 3101 Biochemistry and cell biology, 3211 Oncology and carcinogenesis

Abstract:

In a recent clinical study, we showed that hypericin accumulates selectively in urothelial lesions of the bladder following intravesical administration of the compound in patients. This observation infers that hypericin, a potent photosensitizer, could be used as a selective photodynamic therapy (PDT) tool against superficial bladder cancer. In the present study we investigated the in vivo PDT activity of hypericin in transition cell carcinoma (TCC) tumors of the bladder. Both the distribution and tumor PDT response were carried out using subcutaneous heterotopic AY-27 TCC tumors in syngeneic rats. For both PDT and distribution studies, hypericin (1 or 5 mg/kg) was injected intravenously 0.5, 6 or 24 h before PDT or distribution evaluation. The data show that hypericin is a potent photosensitizer in the treatment of TCC tumors in vivo and that the interval between drug administration and photo-irradiation has a dramatic effect on the PDT outcome. Using a 0.5 h interval between drug administration and photo-irradiation the tumor regrowth study indicated that no tumor mass could me measured 9-10 days after PDT. On the contrary, lengthening the time interval between drug administration and photo-irradiation resulted in a gradual loss of PDT efficiency in these tumors. For instance, while the 6 h drug interval protocol produced a moderate PDT activity in which the tumor sizes decreased to about 50% of their original sizes 11-16 days after photo-irradiation, the 24 h interval protocol was even less effective. The distribution data indicate that the PDT efficiency of hypericin in TCC tumors corresponded to the plasma concentrations rather than to the over all concentrations in the tumor. It is therefore conceivable that the mechanism of PDT efficacy of hypericin in TCC tumors is through indirect (vascular effects) rather than through direct effects (cellular destruction) of hypericin in these tumors. In conclusion, our data indicate that hypericin is a potent photosensitizer against AY-27 TCC tumors and that the PDT efficacy of hypericin is largely determined by photosensitizer distribution in the tumor at the time of photo-irradiation.