PHOTOIMMUNOTHERAPY AND BIODISTRIBUTION WITH AN OC125-CHLORIN IMMUNOCONJUGATE IN AN IN-VIVO MURINE OVARIAN-CANCER MODEL

Photodynamic therapy (PDT) is an experimental approach to the treatmen t of neoplasms in which photosensitisers (PSs) accumulated in malignan t tissues are photoactivated with appropriate wavelengths of light. Th e target specificity of PSs may be improved by linking them with carri er macromolecules such as monoclonal antibodies (MAbs). OC125 is a mur ine MAb that recognises the antigen CA 125, which is expressed on 80% of non-mucinous ovarian tumours. A chlorin derivative conjugated to OC 125 was shown to be selectively phototoxic to ovarian cancer and other CA 125-positive cells in vitro and ex vivo. We now report in vivo stu dies using an ascitic Balb/c nude mouse ovarian cancer model. Ascites was induced by intraperitoneal injection of cells from the human ovari an cancer cell line NIH:OVCAR3. Six weeks after injection, when the an imals had developed ascites, biodistribution studies were carried out by injecting the immunoconjugate (IC) or free PS intraperitoneally and sacrificing the animals at 3, 6, 12, 24, 48, 72 and 168 h later. The PS was quantitated by extraction and fluorescence spectroscopy. For bo th the IC and free PS, peak tumour concentrations were reached at 24 h ; however, the absolute concentrations for the IC were always higher ( 2- to 3-fold) than the free PS. Tumour to non-tumour ratios at 24 h fo r the IC were 6.8 for blood, 6.5 for liver, 7.2 for kidney, 5.7 for sk in and 3.5 for intestine. Evaluation of Viable tumour cells in ascites following in vivo PDT with a single light exposure demonstrated a dos e-dependent relationship with fluence and IC concentration. However, t here was significant treatment-related toxicity at all fluences. With multiple low-dose treatments, the percentage of viable tumour cells wa s also significantly reduced and there were no treatment-related death s. These data suggest that, while photoimmunotherapy remains promising as a new treatment modality for ovarian cancers, careful quantitative dosimetry of both IC and light may need to be combined with multiple treatments (as with radiation therapy and chemotherapy) to control mal ignant disease yet maintain acceptable toxicity in vivo.