Experimental assessment of photodynamic therapy with chlorins for malignant mesothelioma

Our plain-English summary of Experimental assessment of photodynamic therapy with chlorins for malignant mesothelioma, by H.B. Ris, A. Giger, V.I. Hof, et al (European Journal of Cardio-thoracic Surgery, 1997).

The study

• Authors: H.B. Ris, A. Giger, V.I. Hof, D. Mettler, J.C. Stewart, U. Althaus, H.J. Altermatt
• Journal: European Journal of Cardio-thoracic Surgery
• Published: 1997;12(4):542-8
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: Photodynamic therapy (PDT) with two chlorin sensitisers was assessed on nude mice bearing human mesothelioma xenografts, and on intrathoracic tissues of minipigs with the same drug-light conditions to optimise the antitumour activity of PDT while preventing photosensitising injury to normal tissues.

Methods: Laser light (20 J/cm2) at 652 nm was delivered to the xenografts 1-4 days after i.p. administration of 0.1 mg/kg m-tetrahydroxyphenyl-chlorin (mTHPC) or an equimolar dose of polyethylene glycol-derived mTHPC (pegylated mTHPC), respectively. The extent of tumour necrosis was assessed by histomorphometry. Intraoperative PDT was then performed to the thoracic cavity of minipigs through a sternotomy with the same drug-light conditions at drug-light intervals ranging from 12 h to 6 days after i.v. administration of mTHPC and pegylated mTHPC, respectively.

Results: Both, mTHPC and pegylated mTHPC, resulted in photosensitised necrosis of mesothelioma xenografts at drug-light intervals from 1 to 4 days but the extent of necrosis was significantly larger by use of pegylated mTHPC instead of mTHPC at a drug-light interval of 3 and 4 days. The optimal tumourcidal effect was achieved with pegylated mTHPC at a drug-light interval of 4 days. The photosensitising effect of mTHPC on intrathoracic tissues of minipigs revealed severe damage of virtually all tissues except nerves at short drug-light intervals. Tissue damage gradually became less at longer drug-light intervals and was absent at intervals of 3 days and longer. In contrast, pegylated mTHPC resulted in no obvious change to any structure at any drug-light interval assessed.

Conclusions: PDT with pegylated mTHPC reveals the potential of selective tumour destruction in this experimental setting and deserves further evaluation for intraoperative application in patients with malignant mesothelioma.

In plain English

This Swiss animal experiment tested photodynamic therapy (a light-sensitive drug followed by laser light) for malignant mesothelioma. The study did not examine asbestos exposure. Forty-eight nude mice with human mesothelioma tumours under the skin received 0.1 mg/kg mTHPC or a modified form, pegylated mTHPC, dosed to supply the same amount of active mTHPC, then laser light 1 to 4 days later. Both caused areas of tumour tissue death (necrosis). Pegylated mTHPC caused significantly more necrosis at 3 days (P=0.03) and 4 days (P=0.005), with its largest effect at 4 days. The same drug and light doses were then used in the chests of 14 tumour-free minipigs, given the drugs into a vein, with light 12 hours to 6 days later. With mTHPC, short intervals severely damaged virtually all chest tissues except nerves; from 3 days on, only minor changes such as inflammatory changes remained. Pegylated mTHPC caused only minor changes. The authors concluded that pegylated mTHPC showed potential for selective tumour destruction in this setting. They noted the mouse tumours did not invade nearby tissue as mesothelioma does in patients.

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 mesothelioma xenografts, and tumour-free minipigs)
• Who was studied: 48 BALB/c nude mice with subcutaneous human malignant mesothelioma xenografts (24 per drug, 6 per drug-light interval) and 14 tumour-free minipigs (7 per drug, one pig per drug and per drug-light interval), University of Bern, Switzerland
• Exposure: No asbestos exposure was studied. The animals received photodynamic therapy with 0.1 mg/kg m-tetrahydroxyphenyl-chlorin (mTHPC) or an equimolar dose of pegylated mTHPC, which supplied the same amount of active mTHPC. They then received 652 nm laser light at 20 J/cm2. Mice were injected intraperitoneally and given light 1 to 4 days after the drug. Minipigs were given the drug intravenously and light 12 h to 6 days after the drug.
• Main results:
  • In mice, mTHPC produced substantial tumour necrosis at drug-light intervals of 1 to 4 days, with no significant differences between these time points.
  • In mice, pegylated mTHPC produced significantly more tumour necrosis than mTHPC at drug-light intervals of 3 days (P=0.03) and 4 days (P=0.005).
  • In mice given pegylated mTHPC, tumour necrosis was significantly larger at a 4-day interval than at 1 day (P=0.02), 2 days (P=0.04) and 3 days (P=0.01).
  • In minipigs given mTHPC, short drug-light intervals caused severe damage to virtually all chest tissues except nerves. Nerves did show edema and thrombosed perineural vessels at 12 and 24 h. The severe damage lessened at longer intervals. Some minor changes remained at longer intervals, including discrete perivascular leucocytic infiltrations in skin at 3 days and longer and pericarditis without myocardial necrosis at 24 h and longer.
  • In minipigs given pegylated mTHPC, tissue changes were minor. At the 12 h interval these included minor lung edema, slight alveolitis and small scattered foci of pericardial fat necrosis. Discrete perivascular leucocytic infiltrations were seen in skin at intervals of 12 h to 3 days.
  • In minipigs given mTHPC with drug-light intervals of 12 h to 3 days, food intake was reduced and behaviour was disturbed after surgery.
• The authors' conclusion: The authors concluded that photodynamic therapy with pegylated mTHPC showed the potential for selective tumour destruction in this experimental setting and deserved further evaluation for use during surgery in patients with malignant mesothelioma.
• Limitations the authors state:
  • The subcutaneous mouse xenografts do not reflect how malignant mesothelioma grows in patients, because they do not invade locally.
  • The effect on locally invasive mesothelioma, or on tumour remnants left after surgery, is not yet known.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Mesothelioma, Intrathoracic, Necrosis.

Related studies

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• Photodynamic therapy as adjuvant therapy in surgically treated pleural malignancies — P. Baas, L. Murrer, et al. (1997)
• 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)
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• Modeling Epidermal Growth Factor Inhibitor-mediated Enhancement of Photodynamic Therapy Efficacy Using 3D Mesothelioma Cell Culture — G. Cramer, M. Shin, et al. (2019)

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