Distribution of temoporfin, a new photosensitizer for the photodynamic therapy of cancer, in a murine tumor model.
The biodistribution of temoporfin (tetra[m-hydroxyphenyl]chlorin, m-THPC), a recently developed photosensitizer, was investigated in BALB/c mice. The drug was administered intravenously (0.35-0.75 mumol/kg) to tumor-free mice or to mice implanted with the Colo 26 colorectal carcinoma. Blood and tissue samples were collected for up to 96 h post-dose. Drug concentrations were determined by HPLC coupled to photometric detection at 423 nm. Concentrations in blood and liver fell relatively rapidly such that blood concentrations at later time points were below the limit of detection. Tumor concentrations rose at first and then remained constant from 24 h. Temoporfin concentrations in some tissues, notably heart and skeletal muscle, declined only slowly when compared to blood. The tumor: tissue ratios for those organs that showed a more rapid decline in temoporfin concentrations were higher at later times, whereas in tissues such as muscle the ratio remained relatively constant. The organs with the highest tumor:tissue ratios were small intestine (8.6), liver (6.9) and skeletal muscle (5.0).
Whelpton
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R
Department of Pharmacology, Queen Mary and Westfield College, University of London, UK.
Michael-Titus
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AT
Basra
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SS
Grahn
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M
D000818:Animals; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D008652:Mesoporphyrins / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin