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 ∼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 μM. 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 λ 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.
Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland. jdabrows@chemia.uj.edu.pl
Janusz M
JM
Dąbrowski
Krystyna
K
Urbanska
Luis G
LG
Arnaut
Mariette M
MM
Pereira
Artur R
AR
Abreu
Sérgio
S
Simões
Grażyna
G
Stochel
D000818:Animals; D045744:Cell Line, Tumor; D054879:Halogenation; D007274:Injections, Intraperitoneal; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011166:Porphyrins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; C452433:bacteriochlorin