Rhodamine-123 as a new laser dye: in vivo study of dye effects on murine metabolism, histology and ultrastructure.
Rhodamine-123 (Rh-123) is a mitochondrial-specific dye that has recently proven to be an effective fluorochrome for photo-dynamic therapy of squamous carcinoma cells and melanomas with the Argon laser. Complete eradication of heterotransplanted human tumors in nude mice was possible if tumors were first "sensitized" to Rh-123 and then treated with the Argon laser. Prior to initiation of human testing of this technique, the toxicity and pathological changes in BALB/c mice were tested by an escalating dose schedule after systemic injection of Rh-123. Animals' body weight, blood chemistry, enzymes and organ evaluation for histology, and ultrastructural changes were analyzed for 3 weeks after injection with Rh-123. The results of this study demonstrate that Rh-123 has significant systemic toxicity in BALB/c mice injected at doses of 10 micrograms/g of body weight and above, manifested by chronic weight loss and elevation of muscle enzymes with death of the animals injected at doses higher than 50 micrograms/g of body weight. At doses of 1 micrograms/g of Rh-123, no local or systemic toxicity was observed even after a 3-week follow-up, suggesting that safe and effective tumor sensitization might be possible in humans at this concentration. The high effectiveness of this new technique of photodynamic therapy and the low toxicity of this dye in this preclinical model system suggests that Rh-123 and the Argon laser may represent a powerful new method for treatment of superficial malignancies.
Castro
D J
DJ
Division of Head and Neck Surgery Otolaryngology, UCLA School of Medicine 90024-1624.
Saxton
R E
RE
Rodgerson
D O
DO
Fu
Y S
YS
Bhuta
S M
SM
Fetterman
H R
HR
Castro
D J
DJ
Tartell
P B
PB
Ward
P H
PH
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy; D020112:Rhodamine 123; D012235:Rhodamines / Q000633:toxicity*; D015431:Weight Loss / Q000187:drug effects; D014966:Xanthenes / Q000633:toxicity*
D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D012235:Rhodamines; D014966:Xanthenes; D020112:Rhodamine 123