Photofrin as a specific radiosensitizing agent for tumors: studies in comparison to other porphyrins, in an experimental in vivo model

• Published in: Journal of photochemistry and photobiology. B, Biology Vol. 66; no. 3; pp. 157 - 164
• Main Authors: Schaffer, M., Schaffer, P.M., Corti, L., Gardiman, M., Sotti, G., Hofstetter, A., Jori, G., Dühmke, E.
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 01.04.2002
• Subjects: Animals; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Dihematoporphyrin Ether - pharmacokinetics; Dihematoporphyrin Ether - therapeutic use; Female; Humans; Ionizing irradiation; Mice; Mice, Nude; Photofrin II; Photosensitizer; Porphyrins; Porphyrins - therapeutic use; Radiation-Sensitizing Agents - therapeutic use; Radiosensitizer; Radiotherapy Dosage; Tissue Distribution; Transplantation, Heterologous; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - pathology; Radiosensitizer; Ionizing irradiation; Photofrin II; Photosensitizer; Porphyrins
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/S1011-1344(02)00237-3

The use of ionizing radiation for tumor treatment represents a well established therapeutic modality. The efficiency and selectivity of radiotherapeutic protocols can be often enhanced by the addition of specific chemical compounds that optimise the response of the tumor to the incident radiation as compared with peritumoral tissue districts. The results of this study showed that Photofrin, a porphyrin derivative which is presently used as a tumor-photosensitizing agent in photodynamic therapy (PDT), can also act as an efficient tumor radiosensitizer. To test this possibility, we used nude mice subcutaneously implanted with human bladder cancer RT4. The mice were injected with different porphyrin-type photosensitizing agents, including Photofrin, 5-aminolevulinic acid, chlorin e 6, haematoporphyrin, protoporphyrin, Zn-tetrasulphophtalocyanine, and irradiated with 5 and 15 Gy using a Siemens X-ray device. Even though all the porphyrins accumulated in significant amounts in the neoplastic lesion, only Photofrin significantly improved the response of the tumor to irradiation by increasing the doubling time of the tumor volume from 6.2 days in the untreated control group to 10.9 days in the 5 and 15 Gy-irradiated groups. The tumor response was maximal with injected Photofrin doses of 7.5 mg/kg, and was not further enhanced by injection of higher doses. Our hypothesis is, that the radiosensitizing effect of Photofrin seems to be due to some oligomeric constituents which could specifically react with radiogenerated-radicals thereby amplifying the effect of the X-ray radiation.