Biodistribution and Photodynamic Efficacy of a Water-Soluble, Stable, Halogenated Bacteriochlorin against Melanoma

The in vitro phototoxicity of a photostable, synthetic, water-soluble, halogenated bacteriochlorin, 5,10,15,20-tetrakis(2-chloro-5-sulfophenyl) bacteriochlorin (TCPBSO3H), toward mouse melanoma (S91) cells is similar to 60-fold higher than that of the analogous porphyrin, and is associated with very weak toxicity in the dark; 90% of S91 cells were killed in response to a light dose of 0.26 J cm(-2) in the presence of [TCPBSO3H] = 5 mu m. In vivo toxicity toward DBA mice is very low, even at doses of 20 mg kg(-1). In vivo pharmacokinetics and biodistribution of TCPBSO3H were studied in DBA mice with S91 tumors; 24 h after intraperitoneal injection of 10 mg kg(-1), TCPBSO3H demonstrated preferential accumulation in S91 mouse melanoma, with tumor-to-normal tissue ratios of 3 and 5 for muscle and skin, respectively. Photodynamic therapy (PDT) performed under these conditions, with 90 mW cm(-2) diode laser irradiation at lambda 750 nm for 20 min (total light dose of 108 J cm(-2)), resulted in tumor regression. Tumor recurrence was observed only approximately two months after treatment, confirming the efficacy of this PDT against melanoma.