MULTIPLE MODALITY TREATMENT OF CARCINOMA-CELLS WITH PT(RH-123)2 PLUS X-RAY PLUS LIGHT

A complex of platinum tetrachloride with two molecules of rhodamine-123 (Rh-123), Pt(Rh-123)2, has been reported to act as hypoxic cell radiosensitizer of carcinoma cells in vitro and in vivo. In the present paper we report that Pt(Rh-123)2 photosensitizes human mammary carcinoma (MCF-7) cells and cis-platinum resistant human mammary carcinoma (MCF-7/CP) cells to 400-800 nm light in vitro. The efficiency of photosensitization by Pt(Rh-123)2 was 10 times greater than for Rh-123. Combination therapy using Pt(Rh-123)2 plus x-ray plus light was also much more effective compared to the combination therapy using Rh-123 plus x-ray plus light. After 15-mu-M of Rh-123 plus x-ray (0-8 Gy) plus light (5 J/cm2) treatment, cell survival curve was parallel to the x-ray cell survival curve with an initial decrease in the surviving fraction corresponding to the drug plus light mediated killing. Cell killing caused by Rh-123 (15-mu-M) plus x-ray (0-8 Gy) plus light (5 J/cm2) was additive as determined by the product of the surviving fraction after Rh-123 plus light and x-ray. In contrast, for 15-mu-M of Pt(Rh-123)2 plus x-ray (8 Gy) plus light (5 J/cm2) treatment, whereas additive killing predicts a survival fraction of approximately 0.024, in reality, the combination therapy caused the survival fraction to decrease to 0.0012, implying that the cell killing was enhanced by a factor of 20. Using Pt(Rh-123)2 plus x-ray plus light, supraadditive cell killing was also observed under hypoxic conditions, although compared to normally oxygenated conditions the degree of cytotoxicity was significantly reduced. These results indicate that the platinum-Rh-123 complex acts as a photo- and radiosensitizer and should be a highly effective drug for use with combined photo and x-irradiation.