serval:BIB_0203F1751D9E
Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts.
10.1038/sj.bjc.6690170
000078699500010
10098737
Ris
H.B.
author
Krueger
T.
author
Giger
A.
author
Lim
C.K.
author
Stewart
J.C.
author
Althaus
U.
author
Altermatt
H.J.
author
article
1999
British Journal of Cancer
0007-0920
0007-0920
journal
79
7-8
1061-1066
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.
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
eng
60_published
true
peer-reviewed
Publication types: Comparative Study ; Journal Article
Publication Status: ppublish
University of Lausanne
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