Synthesis of New Hematoporphyrin Derivatives Providing a Tumor-Specificity

Research Project

Project/Area Number	59870053
Research Category	Grant-in-Aid for Developmental Scientific Research
Allocation Type	Single-year Grants
Research Field	Urology
Research Institution	Akita University School of Medicine
Principal Investigator	KATO Tetsuro Akita Univ. School Med., Associate Professor, 医学部, 助教授 (40004642)
Co-Investigator(Kenkyū-buntansha)	MORI Hisashi Akita Univ. School Med., Teaching Staff, 医学部, 助手 (10166366) 鈴木敏夫秋田大学, 医学部, 助教授 (20108559) UNNO Katsuo Akita Univ. School Med., Professor, 医学部, 教授 (40111322)
Project Period (FY)	1984 – 1986
Project Status	Completed (Fiscal Year 1986)
Budget Amount *help	¥6,700,000 (Direct Cost: ¥6,700,000) Fiscal Year 1986: ¥1,000,000 (Direct Cost: ¥1,000,000) Fiscal Year 1985: ¥1,900,000 (Direct Cost: ¥1,900,000) Fiscal Year 1984: ¥3,800,000 (Direct Cost: ¥3,800,000)
Keywords	Hematoporphyrin deribatives / Hematoporfhyrin diacetate / Hematoporphyrin disilate / Synthesis / Tumor affinity / 体内分布
Research Abstract	Hematoporphyrin derivative (Hp-D)is known to accumulate in tumor tissues and exert a photodynamic action. But this is an unstable complex mixture, so that it is still undetermined which component has these biological activities. Hematoporphyrin diacetate (Hp-Ac, <C_(38)H_(42)O_8N_4> , NW 682) a main component of Hp-D before alkali-treatment, and hematoporphyrin disilate (Hp-Si, <C_(46)H_(66)O_6N_4Si_2> , MW 826). a new compound, were synthesized as a single chemical agent and their properties were verified. Hp-Ac and Hp-Si, as like Hp-D, are well incorporated into human bladder cancer cells in vitro as well as into rat ascite tumor cells by intravenous administration. Hp-Ac, Hp-Si and Hp-D, after intravenous injection into tumor-bearing rats (is-iv), show in general a trend of tissue distrubution in the following order: liver, Spleen>tumor, Kidney, lung>testis, muscle. Hp-Ac and Hp-D levels in these tissues gradually decrease, while Hp-Si retains for a longer period of time up to 96 hours after injection. The tumor/surrounding muscle ratio of porphyrin concentraion (T/M ratio) ranges from 2.7 to 7.5 for Hp-D and from 3.7 to 6.6 for Hp-Si, indicating a high intratumorous accumlation of these two substances. On the other hand, T/M value of Hp-Ac remains at a low level ranging 1.0 to1.7. The present investigation indicates the possible usefulness of Hp-Si as a porphyrin derivative which has a high tumor affinity. Since Hp-Si is a single chemical compound, this substance may be used as a photosensitizer in photoradiation therapy but also as a drug carrier in tragenting cancer chemotherapy.