Tissue uptake study and photodynamic therapy of melanoma-bearing mice with a nontoxic, effective chlorin.

Abstract

Chlorins have intense red absorptions and high tumor affinities that make them interesting candidates for photodynamic therapy (PDT) of cancer. This paper reports cytotoxicity, phototoxicity, in vitro cellular uptake, and in vivo biodistribution and PDT efficacy of a synthetic chlorin derivative (TCPCSO₃H) towards Cloudman melanoma cells (S91). No cytotoxic effects were observed in vitro at concentrations up to 20 μm, and no toxicity was observed in vivo in DBA mice with doses up to 2 mg kg⁻¹. Pharmacokinetics and biodistribution of TCPCSO₃H were evaluated in vivo in DBA mice bearing S91 tumors. TCPCSO₃H demonstrated preferential accumulation in S91 mouse melanoma, with tumor-to-normal tissue ratios of 5 and 11 for muscle and skin, respectively, 24 h after intravenous injection of 2 mg kg⁻¹. Photodynamic therapy performed under these conditions with 70 mW cm⁻² diode laser irradiation at 655 nm for 25 min (total light dose=105 J cm⁻²) resulted in scab formation, followed by temporary or permanent (>60 days) tumor remission. According to the Kaplan-Meier analysis, the median survival time of the control group was 9 days, whereas that of the treated group was 38 days.

• Authors: Janusz M Dąbrowski, Martyna Krzykawska, Luis G Arnaut, Mariette M Pereira, Carlos J P Monteiro, Sérgio Simões, Krystyna Urbańska, Grażyna Stochel
• Journal: ChemMedChem (ChemMedChem) Vol. 6 Issue 9 Pg. 1715-26 (Sep 05 2011) ISSN: 1860-7187 [Electronic] Germany
• PMID: 21732537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Photosensitizing Agents
• Porphyrins
• chlorin

Topics

• Animals
• Apoptosis (drug effects, radiation effects)
• Cell Line, Tumor
• Injections, Intravenous
• Lasers
• Melanoma, Experimental (drug therapy, metabolism, pathology)
• Mice
• Mice, Inbred DBA
• Photochemotherapy (methods)
• Photosensitizing Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Porphyrins (administration & dosage, pharmacokinetics, therapeutic use)
• Radiation Dosage
• Spectrometry, Fluorescence
• Time Factors
• Tissue Distribution