tetra(4-n-methylpyridyl)porphine and Fibrosarcoma

The meso-substituted cationic porphyrin, meso-tetra(4N-methyl-pyridyl)porphine (T4MPyP) appears to be a selective tumour localizer on the basis of pharmacokinetic studies. Irradiation (at 600-680 nm) of an intramuscularly implanted MS-2 fibrosarcoma in Balb/c mice at 24 h after injection of T4MPyP causes tumour necrosis: histological and ultrastructural analyses of tumour specimens taken at different times after phototherapy indicate slowly-appearing tissue damage which involves both malignant cells and the vascular endothelium. At the subcellular level, the membranous systems and nuclei are the main targets of the photoprocess. The tumour necrosis is particularly extensive upon injection of 4.1 mg kg-1 T4MPyP.

Topics: Animals; Endothelium, Vascular; Female; Fibrosarcoma; Mesoporphyrins; Mice; Mice, Inbred BALB C; Microscopy, Electron; Necrosis; Photochemotherapy; Porphyrins; Time Factors

The pharmacokinetic behaviour and the photodynamic properties of the cationic porphyrin meso-tetra(4N-methylpyridyl)porphine (T4MPyP 2.1 mg/kg) were examined in Balb/c mice bearing an MS-2 fibrosarcoma. The porphyrin shows good tumour localizing properties; 24 h after drug administration the tumour concentration of T4MPyP was approximately 1.2 ng/mg, while the concentrations in normal tissues were substantially lower, except for liver and spleen. In the serum, T4MPyP is preferentially transported by albumin and globulins (80.5%), while minor amounts are associated to lipoproteins (19.5%). The phototherapeutic efficiency of T4MPyP was tested by following the growth curves of fibrosarcoma irradiated by 600-680 nm (450 J/cm2) 24 h after the i.v. injection of T4MPyP (2.1 mg/kg). PDT-treated tumours showed a temporary delay in their growth compared with control tumours. The excellent selectivity of T4MPyP and its antitumour activity on photoexcitation encourage further studies for assessing the usefulness of this porphyrin in photodynamic therapy.

Topics: Animals; Female; Fibrosarcoma; Mesoporphyrins; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Photochemotherapy; Photosensitizing Agents; Porphyrins; Rabbits; Tissue Distribution