Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts.

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Serval ID
serval:BIB_0203F1751D9E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts.
Journal
British Journal of Cancer
Author(s)
Ris H.B., Krueger T., Giger A., Lim C.K., Stewart J.C., Althaus U., Altermatt H.J.
ISSN
0007-0920 (Print)
ISSN-L
0007-0920
Publication state
Published
Issued date
1999
Peer-reviewed
Oui
Volume
79
Number
7-8
Pages
1061-1066
Language
english
Notes
Publication types: Comparative Study ; Journal Article
Publication Status: ppublish
Abstract
The photosensitizing properties of m-tetrahydroxyphenylchlorin (mTHPC) and polyethylene glycol-derivatized mTHPC (pegylated mTHPC) were compared in nude mice bearing human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts. Laser light (20 J/cm2) at 652 nm was delivered to the tumour (surface irradiance) and to an equal-sized area of the hind leg of the animals after i.p. administration of 0.1 mg/kg body weight mTHPC and an equimolar dose of pegylated mTHPC, respectively. The extent of tumour necrosis and normal tissue injury was assessed by histology. Both mTHPC and pegylated mTHPC catalyse photosensitized necrosis in mesothelioma xenografts at drug-light intervals of 1-4 days. The onset of action of pegylated mTHPC seemed slower but significantly exceeds that of mTHPC by days 3 and 4 with the greatest difference being noted at day 4. Pegylated mTHPC also induced significantly larger photonecrosis than mTHPC in squamous cell xenografts but not in adenocarcinoma at day 4, where mTHPC showed greatest activity. The degree of necrosis induced by pegylated mTHPC was the same for all three xenografts. mTHPC led to necrosis of skin and underlying muscle at a drug-light interval of 1 day but minor histological changes only at drug-light intervals from 2-4 days. In contrast, pegylated mTHPC did not result in histologically detectable changes in normal tissues under the same treatment conditions at any drug-light interval assessed. In this study, pegylated mTHPC had advantages as a photosensitizer compared to mTHPC. Tissue concentrations of mTHPC and pegylated mTHPC were measured by high-performance liquid chromatography in non-irradiated animals 4 days after administration. There was no significant difference in tumour uptake between the two sensitizers in mesothelioma, adenocarcinoma and squamous cell carcinoma xenografts. Tissue concentration measurements were of limited use for predicting photosensitization in this model.
Keywords
Adenocarcinoma/drug therapy, Adenocarcinoma/metabolism, Animals, Antineoplastic Agents/chemistry, Antineoplastic Agents/pharmacokinetics, Carcinoma, Squamous Cell/drug therapy, Carcinoma, Squamous Cell/metabolism, Dermatitis, Phototoxic/etiology, Dermatitis, Phototoxic/pathology, Humans, Mesoporphyrins/chemistry, Mesoporphyrins/pharmacokinetics, Mesothelioma/drug therapy, Mesothelioma/metabolism, Mice, Mice, Inbred BALB C, Mice, Nude, Neoplasms/drug therapy, Neoplasms/metabolism, Photochemotherapy/methods, Polyethylene Glycols/chemistry, Polyethylene Glycols/pharmacokinetics, Radiation-Sensitizing Agents/chemistry, Radiation-Sensitizing Agents/pharmacokinetics, Transplantation, Heterologous
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2008 13:59
Last modification date
20/08/2019 13:24
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