[Basic study for cancer therapy with porphyrin derivatives and pheophorbide derivatives]

The properties of Porphyrin and Pheophorbide derivatives with cyclic tetrapyrrole structure have a specific character to accumulate selectively in tumor tissues and destruct tumor cells by photodynamic action. Recently, Photoradiation therapy of cancer with Porphyrin derivatives has put into practice, but its indication is very limited. We examined fundamentally on tumor tissue affinity of various Porphyrin and Pheophorbide derivatives, aiming at expanding therapeutic indication and application. As materials we used 73 derivatives in total, including 14 Porphyrin derivatives, 32 Pheophorbide derivatives, 17 Porphyrin metal complex and 10 Pheophorbide metal complex, and examined about the relation between their side branches and their tumor tissue affinity by N2-pulsed Laser spectrofluorometry, using tumor-bearing Golden Hamster. Furthermore, we investigated substances connected with Hematoporphyrin derivatives (HPD) in tumor cells. As a result, we had the following conclusions. N2-pulsed Laser spectrofluorometry is useful for analysis of Porphyrin and Pheophorbide derivatives in vivo. In Porphyrin derivatives, those with dimer structure and acetyl radical have higher tumor tissue affinity than those without such structures. Existence of OH radical and dimer structure is dispensable for tumor tissue affinity of Pheophorbide derivatives. OH radical in Porphyrin metal complex and acetyl radical in Pheophorbide metal complex are important factors for tumor tissue affinity of them. It is suggested that Hematoporphyrin derivatives (HPD) in vivo combine with protein in tumor cells.