Tumors of diverse histology are sensitive to rhodamine 123 laser phototherapy in vitro

Abstract

Rhodamine 123 has been shown to be an efficient photosensitizer for the argon laser treatment of a human squamous carcinoma and a melanoma cell line in vitro. Rhodamine 123 laser phototherapy also eradicates these human squamous cell carcinomas when grown as subcutaneous tumor transplants in athymic mice. This study extends these observations by testing a panel of 19 human tumor cell lines of various histologic origins for in vitro sensitivity to rhodamine 123 and the argon laser. Rhodamine 123 with an absorption maxima of 502 nm in water was found to undergo a redshift to 516 nm after uptake by the mitochondria of human tumor cells. Rhodamine 123-sensitized brain tumor cells were inhibited by over 80% after 15 seconds and by 98% after 60 seconds of laser exposure (514.5 nm, 4 W, T max = 39°C), as measured by reduced [ 3H]thymidine incorporation into cellular DNA. Laser or rhodamine 123 alone did not significantly inhibit (>20%) tumor cell [ 3H]thymidine uptake. Sensitization with 20 μg rhodamine 123 for 1 hour before 45 seconds of laser illumination decreased cell [ 3H]thymidine uptake by 40% to 99% in four melanoma lines, five carcinomas, five leukemias, and four of five other human tumor lines. Two melanomas, two leukemias, and a lymphoma cell line also exhibited a 70% to 80% reduction in [ 3H]thymidine uptake after sensitization in vitro with 1 μg/mL rhodamine 123 and laser illumination. Rhodamine 123-sensitized tumor cells were inhibited even more strongly by fractional dose laser irradiation at nonthermal temperatures. These results provide evidence that rhodamine 123 is an effective tumor targetting reagent in the laser photodynamic treatment of many types of malignant human cells in vitro, and suggest that cationic rhodamine laser dyes may be a useful new class of photosensitizers in the treatment of cancer.