Foscan uptake and tissue distribution in relation to photodynamic efficacy

Our plain-English summary of Foscan uptake and tissue distribution in relation to photodynamic efficacy, by P. Cramers, M. Ruevekamp, H. Oppelaar, et al (British Journal of Cancer, 2003).

The study

• Authors: P. Cramers, M. Ruevekamp, H. Oppelaar, O. Dalesio, P. Baas, F.A. Stewart
• Journal: British Journal of Cancer
• Published: 2003;88(2):283-90
• Cited by: 111 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Clinical photodynamic therapy (PDT) schedules are based on the assumption that optimum drug-light intervals are times at which there is a maximum differential between photosensitiser retention in the tumour and surrounding normal tissue. However, vascular-mediated effects contribute to tumour destruction by PDT; therefore, plasma sensitiser levels and endothelial cell drug exposure could also be important determinants of PDT response. The purpose of this study was to investigate the influence of tumour, tissue and plasma concentrations of the photosensitiser Foscan (meta-tetrahydroxyphenylchlorin, mTHPC) on PDT response. Groups of BalbC nude mice, bearing human mesothelioma xenografts (H-MESO1) were injected (i.v.) with a single dose of (14)C-labelled mTHPC, or with two doses, separated by 72 h. Drug levels in plasma, tumour and normal tissues were measured at 5 min to 120 h after drug administration. The PDT tumour and skin responses were evaluated by illuminating separate groups mice at intervals of 5 min to 120 h after injection of Foscan (nonlabelled). Drug levels in both tumour and skin increased during the first 24 h after a single injection, and remained almost constant for at least 120 h. The second injection produced a further, rapid increase in mTHPC levels in tumours and skin, with steady state being maintained from 20 min to 120 h. By contrast, PDT response of both tumours and skin were maximal for illumination at 1-3 h after drug, with very little response when illumination was given 48-120 h after drug. There was no significant correlation between tumour or skin drug level and PDT response. There was, however, a significant correlation between plasma drug levels and tumour or skin response, excluding an initial distribution time of 20 min. These studies demonstrate a pronounced disassociation between tumour drug levels and optimum drug-light intervals for PDT response with Foscan. We suggest that the PDT effect, in both tumours and normal tissues, is largely mediated via vascular damage and that the selectivity of PDT is not based on differential tumour drug uptake.

In plain English

This was an animal experiment on photodynamic therapy (PDT), in which a light-sensitive drug is given and the tumour is then lit with laser light. It did not study asbestos exposure. Female nude mice carried implanted human mesothelioma tumours (H-MESO1). The mice received the drug Foscan (mTHPC) into a vein, either once or twice 72 hours apart. Drug levels in blood plasma, tumour, skin and other organs were measured from 5 minutes to 120 hours later, and separate groups of mice were lit with red light at the same time points. After one dose, drug levels in tumour and skin rose over the first 24 hours and then stayed constant to 120 hours. Even so, treatment worked best when light was given 1, 3 or 6 hours after the drug. At these times, 70% of mice (one dose) or 60% (two doses) were cured with the highest light dose. Light given more than 24 hours after the drug was ineffective. Tumour response did not follow tumour drug levels. It did follow plasma levels once the first 20 minutes after injection were excluded. The authors suggested the treatment works mainly through damage to blood vessels.

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 (mice) comparing drug distribution over time with tumour and skin response to photodynamic therapy
• Who was studied: Female nude BalbC mice (21 to 30 g, aged 12 to 26 weeks) with implanted human mesothelioma xenografts (H-MESO1). Groups were six mice for drug-level measurements, eight per group for tumour treatment and six per group for skin treatment. The work was done at The Netherlands Cancer Institute, Amsterdam.
• Exposure: No asbestos exposure was studied. The mice received the photosensitiser Foscan (mTHPC), 0.3 mg per kg, injected into a vein once, or twice 72 hours apart (radiolabelled drug for the drug-level measurements). This was followed by 652 nm red laser light at light doses of 5, 10 or 30 J per square centimetre, given from 5 minutes to 120 hours after injection.
• Main results:
  • After a single injection, drug levels in tumour and skin rose over the first 24 hours and then stayed constant until 120 hours.
  • In these mice, the drug cleared from plasma in two phases, with half-lives of 1.3 hours and 20.9 hours.
  • Tumour illumination at 1, 3 or 6 hours after the drug was most effective. At these times, with 30 J per square centimetre, 70% of mice (single injection) or 60% (double injection) were cured of their tumours.
  • Illumination more than 24 hours after the drug was ineffective, with no cured tumours.
  • Giving two injections did not increase tumour response compared with one injection.
  • After a single dose, the overall correlation between tumour drug levels and tumour response was poor (P = 0.099).
  • The correlation between plasma drug levels and tumour response was not significant when all intervals were included (P = 0.078). It was highly significant (P less than 0.0001) when the first 20 minutes after injection were excluded.
  • Skin damage at 10 J per square centimetre was greatest for illumination 1 to 6 hours after the drug. Skin reactions did not correlate with skin drug levels (P = 0.570). The correlation with plasma drug levels was also not significant (P = 0.111 for intervals of 1 to 72 hours).
• The authors' conclusion: The authors suggested that the tumour-killing effect of Foscan PDT is largely mediated through damage to blood vessels. They also suggested that its selectivity rests on factors other than greater drug uptake by the tumour.
• Limitations the authors state:
  • The authors noted that Foscan behaves differently in rodents and humans: the early rapid clearance from blood seen in rodents does not occur in humans. They also noted that their findings differ from clinical experience.

Topics

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

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

Related studies

• Experimental assessment of photodynamic therapy with chlorins for malignant mesothelioma — H.B. Ris, A. Giger, et al. (1997)
• Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts — H.B. Ris, T. Krueger, et al. (1999)
• Real-time light dosimetry for intra-cavity photodynamic therapy: Application for pleural mesothelioma treatment — N. Betrouni, C. Munck, et al. (2017)
• Photodynamic therapy with chlorins for diffuse malignant mesothelioma: initial clinical results — H.B. Ris, H.J. Altermatt, et al. (1991)
• Photodynamic therapy as adjuvant therapy in surgically treated pleural malignancies — P. Baas, L. Murrer, et al. (1997)
• 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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