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

Our plain-English summary of Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts, by H.B. Ris, T. Krueger, A. Giger, et al (British Journal of Cancer, 1999).

The study

• Authors: H.B. Ris, T. Krueger, A. Giger, C.K. Lim, J.C. Stewart, U. Althaus, H.J. Altermatt
• Journal: British Journal of Cancer
• Published: 1999;79(7-8):1061-6
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This animal experiment compared photodynamic therapy drug mTHPC with a polyethylene glycol-bound version (pegylated mTHPC). It did not study asbestos. Human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma tumours were grown in nude mice; 90 were injected with one drug or the other. Laser light was shone on the tumour and a normal hind-leg area 1 to 4 days later (mesothelioma) or 4 days later (other tumours), in groups of 6. Some were used only for drug-level measurements. At 1 day, mTHPC caused skin and muscle necrosis in normal leg. Pegylated mTHPC caused no histologically recognizable changes at any interval, though a figure caption noted hair follicle depletion at 1 day. In mesothelioma, pegylated mTHPC produced significantly more necrosis than mTHPC at 3 and 4 days (86.3 versus 39.3 square millimetres at 4 days). At 4 days it also did so in squamous cell carcinoma, not adenocarcinoma. Tumour drug levels 4 days after injection did not differ significantly. The authors concluded that pegylated mTHPC had enhanced photosensitizing properties in this model and that tissue drug levels were of little predictive use.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment (nude mice bearing human tumour xenografts) comparing two photodynamic therapy sensitizers
• Who was studied: 90 BALB/c nude mice (45 per drug) bearing human malignant mesothelioma, squamous cell carcinoma of the oral cavity, or adenocarcinoma of the colon xenografts. Irradiated mice were in 12 groups of 6 animals: 8 groups for mesothelioma (4 intervals times 2 drugs), 2 for squamous cell carcinoma and 2 for adenocarcinoma. A further 3 non-irradiated animals per tumour type and drug were used for tissue concentration measurements. There were also 6 non-sensitized, non-irradiated control animals per xenograft type.
• Exposure: No asbestos exposure was studied. The treatment was mTHPC 0.1 mg/kg or an equimolar dose of pegylated mTHPC, injected intraperitoneally. This was followed by 652 nm laser light, 20 J/cm2 at 0.2 W/cm2, given to the tumour and to a hind-leg control site. The drug-light intervals were 1, 2, 3 or 4 days for mesothelioma xenografts and 4 days only for squamous cell carcinoma and adenocarcinoma xenografts.
• Main results:
  • Normal tissue, mTHPC: at a 1-day drug-light interval there was substantial necrosis of skin and underlying muscle (maximum depth of change 2.6 plus or minus 0.6 mm in Table 1). At 2 to 4 days there were only negligible changes (0.1 mm).
  • Normal tissue, pegylated mTHPC: the results text reported no histologically recognizable changes at any drug-light interval (0 in Table 1).
  • Normal tissue, pegylated mTHPC: the Figure 1 caption, for the 1-day interval, describes no obvious alterations except depletion of hair follicles.
  • Mesothelioma xenografts: pegylated mTHPC produced significantly more tumour necrosis than mTHPC at 3 days (53.4 plus or minus 9.6 versus 36.9 plus or minus 16.6 square mm) and at 4 days (86.3 plus or minus 25.1 versus 39.3 plus or minus 27.3 square mm).
  • Mesothelioma xenografts: there was no significant difference between the two drugs at 1 and 2 days.
  • At a 4-day interval, pegylated mTHPC produced significantly more necrosis than mTHPC in squamous cell carcinoma xenografts (58.4 plus or minus 23.3 versus 19.5 plus or minus 3.8 square mm). It did not do so in adenocarcinoma xenografts (81.5 plus or minus 23.4 versus 83.1 plus or minus 37.8 square mm).
  • Tumour drug concentrations did not differ significantly between the two drugs in any of the three xenograft types. These were measured 4 days after injection in non-irradiated animals, 3 per tumour type and drug.
  • At 4 days after injection, pegylated mTHPC concentrations were significantly higher than mTHPC concentrations in heart, lung, spleen and liver, and lower in kidney.
• The authors' conclusion: The authors concluded that pegylated mTHPC showed enhanced photosensitizing properties compared with mTHPC in this model. They also concluded that tissue concentrations measured by HPLC were of little use for predicting photosensitizing effects.
• Limitations the authors state:
  • Xenografts do not reflect how the tumours grow naturally or the environment where they arise in humans.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Squamous Cell Carcinoma, Adenocarcinoma, Necrosis, Histology.

Related studies

• Experimental assessment of photodynamic therapy with chlorins for malignant mesothelioma — H.B. Ris, A. Giger, et al. (1997)
• Photodynamic therapy with chlorins for diffuse malignant mesothelioma: initial clinical results — H.B. Ris, H.J. Altermatt, et al. (1991)
• Foscan uptake and tissue distribution in relation to photodynamic efficacy — P. Cramers, M. Ruevekamp, et al. (2003)
• Effects of photodynamic therapy on xenografts of human mesothelioma and rat mammary carcinoma in nude mice — S.L. Gibson, T.H. Foster, et al. (1994)
• Fluence plays a critical role on the subsequent distribution of chemotherapy and tumor growth delay in murine mesothelioma xenografts pre-treated by photodynamic therapy — Y. Wang, X. Wang, et al. (2015)
• Response of Photofrin-sensitised mesothelioma xenografts to photodynamic therapy with 514 nm light — T.H. Foster, S.L. Gibson, et al. (1996)

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