1996 年 11 巻 2 号 p. 105-110
One of the “dreams” of cancer treatment is missile therapy targeted specifically to cancer tissues. At first, monoclonal antibodies were expected to play primary roles in this therapy and were studied globally at a number of institutions. However, the practical use of monoclonal antibodies is hampered by their poor accumulation in tumor tissues and side effects such as the human antigen-murine antibody reaction (HAMA) phenomenon. Porphyrin derivatives are low-molecular-weight agents that accumulate in tumor tissues and have recently attracted much attention as possible substitutes for monoclonal antibodies We have synthesized about 750 porphyrin-related derivatives since 1980, when we first became interested in the tumor tissue accumulating property of porphyrins, and have studied them in many respects. The mechanisms of tumor tissue accumulation of porphyrins as we speculate at present are followings ; Important factors are the strong affinity of porphyrins to proteins because of their high π electron contents and the amphipathicity to water and oil due to the stacking phenomenon. As for the tumor tissue, active endocytosis associated with enhancement of LDL and transferrin receptor activities and the immaturity or lack of lymphatic tissues in tumor are important factors. The increased permeability of tumor vessels, which has been discussed for years, is also considered to be a factor in tumor tissue accumulation of porphyrins. In this issue, recent knowledge about the mechanism of accumulation of porphyrins in the tumor tissues and the prospects of their application to the diagnosis and treatment of cancer are discussed.