In vitro phototoxicity of a new phthalocyanine-immunoconjugate for use in photodynamic therapy

摘要

Abstract: Non specific localization of photosensitizers after application in vivo limits progress in PDT. Relatively selective distribution of photosensitizers in malignant tissues is crucial for a successful treatment. The target specificity of photosensitizers may be improved by linking photosensitizers with monoclonal antibodies. In this approach, a high specific monoclonal antibody, BM-2 which is directed against epitopes of the mucine glycoprotein TAG-12 was used. This antibody shows reactivity with 96% of all primary breast carcinomas. BM-2 was conjugated with a second generation phthalocyanine photosensitizer which is only weakly phototoxic to human T-47D tumor cells without conjugation in vitro. With respect to future clinical application, illumination times from 25 to 100 minutes and a powerful diode laser with an emission of 690 nm was chosen, which provides deeper tissue penetration in vivo. We observed phototoxicity towards T-47D human breast carcinoma cells at concentrations ranging from 0.25 to 6 micromol/L and light doses from 6 to 24 J/cm$+2$/. The immunoconjugates discriminated mucine-positive and mucine-negative tumor cells and showed high photocytotoxic selectivity towards mucine-positive T-47D cells in vitro. The conjugate showed no dark toxicity. In vivo experiments will follow. !11