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 ($TCPBSO_{3}H$), toward mouse melanoma (S91) cells is ∼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 [$TCPBSO_{3}H$]=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 $TCPBSO_{3}H$ were studied in DBA mice with S91 tumors; 24 h after intraperitoneal injection of 10 mg kg$^{-1}$, $TCPBSO_{3}H$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.