Effect of drug‐light interval on photodynamic therapy with meta‐tetrahydroxyphenylchlorin in malignant mesothelioma

Ris, Hans‐Beat; Altermatt, Hans Jörg; Nachbur, B; Stewart, J. C. M.; Wang, Qiang; Lim, Chang Kee; Bonnett, Raymond; Althaus, U

doi:10.1002/ijc.2910530126

Cited by 98 publications

(81 citation statements)

References 12 publications

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“…The results from this study demonstrated that Foscan PDT was relatively ineffective at controlling the regrowth of H-MESO1 xenografts when illumination was given at intervals of 424 h. This is in agreement with several other studies in rodent tumours and human xenografts grown in nude mice (Ris et al, 1993;Morlet et al, 1995;Van Geel et al, 1995;Veenhuizen et al, 1997a) , but it differs from clinical experience. Standard clinical protocols for Foscan PDT involve illumination with 20 -30 J cm À2 at 4 days after a drug dose of 0.15 mg kg À1 .…”

Section: Discussionsupporting

confidence: 91%

“…Once again, there was an initial distribution time of about 20 min, before illumination effected a PDT response. Other investigators have also reported a general lack of correlation between Foscan uptake in tissue and PDT effect, although most of these studies did not directly compare pharmacokinetics and PDT response (Ris et al, 1993;Morlet et al, 1995;Veenhuizen et al, 1997b).…”

Section: Discussionmentioning

confidence: 99%

“…Several experimental studies have identified a discrepancy between times of maximal tumour drug uptake and optimum illumination intervals for the best tumour effect, both for Foscan and for other photosensitisers (Ris et al, 1993;Morlet et al, 1995;Veenhuizen et al, 1997a, b) . Optimum illumination intervals are usually considerably shorter than times for maximal loading of the tumour with sensitiser.…”

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confidence: 99%

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Foscan® uptake and tissue distribution in relation to photodynamic efficacy

et al. 2003

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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, vascularmediated 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 s (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.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Foscan® uptake and tissue distribution in relation to photodynamic efficacy

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“…At drug-light intervals longer than 4 days after injection, mTHPC disappears almost completely from the vasculature and consequently vascular damage progressively decreases. The results of this study are in agreement with those reported for other types of tumours (Ris et al, 1993a;Lofgren et al, 1994;Peng et al, 1995).…”

Section: Discussionsupporting

confidence: 93%

Photodynamic therapy of early squamous cell carcinoma with tetra(m-hydroxyphenyl)chlorin: optimal drug-light interval

Andrejevic‐Blant

Hadjur²,

Ballini³

et al. 1997

Br J Cancer

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Summary The optimal drug-light interval for effective photodynamic therapy (PDT) of early squamous cell carcinomas was evaluated with tetra(m-hydroxyphenyl)chlorin (mTHPC) by means of two complementary modalities: irradiation tests and ex vivo fluorescence microscopy. A Syrian hamster cheek pouch tumour model was used in these experiments. Photodynamic therapy on both tumour-bearing and contralateral healthy cheek pouch mucosae was performed at 650 nm and 514 nm. Light doses of 12 J cm-2 were delivered at a light dose rate of 150 mW cm-2 and light doses of 80 J cm-2 were delivered at a light dose rate of 100 mW cm-2 respectively, at these two wavelengths, between 6 h and 12 days after the injection of 0.5 mg kg-' body weight mTHPC. Two histologically different types of tissue damage were observed: first, a non-selective and non-specific ischaemic vascular necrosis for the cases in which PDT took place during the first 48 h after the injection of the dye and, second, tissue-specific PDT damage, as a coagulation necrosis, when PDT took place more than 72 h after injection of the dye. The time-dependent biodistribution of mTHPC investigated by fluorescence microscopy shows a weak and non-significant difference in relative fluorescence intensities between early SCC and healthy mucosae. Up to 2 days after the injection, the drug is mainly localized in the endothelial cells of the blood vessels. After this period, the dye accumulates in the squamous epithelia with a concentration peaking at 4 days. At all time points, a weak fluorescence intensity is observed in the underlying lamina propria and striated muscle. The information obtained from these studies could well be relevant to clinical trials as it suggests that time delays between 4 and 8 days after i.v. injection should be optimal for PDT of early malignancies in hollow organs.

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“…These range from the choice of photosensitiser and administration dose, to the time interval before treatment, as well as considering any one of the light dose parameters. Preclinical results indicate that the efficacy of m-THPC is related to both the drug dose and the interval between administration and illumination (Ris et al, 1993a, b). However, the efficacy is also complicated by many in vivo interactions, such as aggregation and protein binding (Glanzmann et al, 1998;Hopkinson et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Photodynamic therapy effect of m-THPC (Foscan®) in vivo: correlation with pharmacokinetics

2003

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m-Tetra(hydroxyphenyl)chlorin (m-THPC, Foscan, Temoporfin) has an unusually high photodynamic efficacy which cannot be explained by its photochemical properties alone. In vivo interactions are therefore of critical importance in determining this high potency. The pharmacokinetics of m-THPC in a rat tumour model was determined using 14 C m-THPC in an LSBD 1 fibrosarcoma implanted into BDIX rats. The photodynamic therapy (PDT) efficacy was determined at different drug administrations to light intervals and correlated with the tumour and plasma pharmacokinetic data. The plasma pharmacokinetics of m-THPC can be interpreted by compartmental analysis as having three half-lives of 0.46, 6.91 and 82.5 h, with a small initial volume of distribution, suggesting retention in the vascular compartment. Tissues of the reticuloendothelial system showed high accumulation of m-THPC, particularly the liver. PDT efficacy of m-THPC over the same time course seemed to exhibit two peaks of activity (2 and 24 h), in terms of tumour growth delay with the peak at 24 h postinjection correlating to the maximum tumour concentration. Investigation on tumour cells isolated from m-THPC-treated tumours suggested that the peak PDT activity at 2 h represents an effect on the vasculature while the peak at 24 h shows a more direct response. These results indicate that the in vivo PDT effect of m-THPC occurs via several mechanisms. British Journal of Cancer (2003) Photodynamic therapy (PDT) is becoming accepted as an alternative to conventional cancer treatments for certain indications and other nononcological conditions. It is based on a tumour accumulation of a photosensitiser, which, when activated by light, results in tumour destruction via reactive oxygen species (Ochsner, 1997). The selectivity of PDT relies upon the targeting of the light delivery in combination with the accumulation/retention of the photosensitiser in malignant tissue. The time interval between photosensitiser administration and light delivery is crucial for the optimal clinical efficacy of PDT. The distribution of the photosensitiser both in the tumour as a whole and throughout the tumour compartments is dependent on this interval as well as in vivo interactions that affect photosensitiser aggregation, delivery and uptake (Boyle and Dolphin, 1996). m-Tetra (hydroxyphenyl)chlorin (m-THPC), a second-generation photosensitiser, has already been shown to be more potent than Photofrin (PII). It has been suggested that it is up to 200 times more powerful (Van Geel et al, 1995;Ball et al, 1999). This figure takes into account the drug dose required (0.15 mg kg À1 compared to 10 mg kg À1 for PII) and the lower light doses necessary (30 J cm À1 rather than 150 J cm À1 ) to produce similar PDT results. However, the reason for this effectiveness remains unresolved even considering the advantageous photoproperties of increased molar absorption coefficient and a favourable shift in the wavelength maximum (652 nm rather than 630 nm) (Bonnett et al, 1989).Preclinical studies have alread...

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Effect of drug‐light interval on photodynamic therapy with meta‐tetrahydroxyphenylchlorin in malignant mesothelioma

Cited by 98 publications

References 12 publications

Foscan® uptake and tissue distribution in relation to photodynamic efficacy

Foscan® uptake and tissue distribution in relation to photodynamic efficacy

Photodynamic therapy of early squamous cell carcinoma with tetra(m-hydroxyphenyl)chlorin: optimal drug-light interval

Photodynamic therapy effect of m-THPC (Foscan®) in vivo: correlation with pharmacokinetics

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