Does tumour uptake of Foscan determine PDT efficacy?

Veenhuizen, Ruth B.; Oppelaar, Hugo; Ruevekamp, Marjan; Schellens, Jan H.M.; Dalesio, Otilia; Stewart, Fiona

doi:10.1002/(sici)1097-0215(19971009)73:2<236::aid-ijc13>3.0.co;2-d

Cited by 38 publications

(44 citation statements)

References 14 publications

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“…There was a much closer correspondence between plasma drug levels and tumour or skin response, except for illumination during the first 20 min after drug delivery. These results are in agreement with our earlier studies on Foscan-mediated response in a rapidly growing murine tumour RIF1 (Veenhuizen et al, 1997a). The previous study also demonstrated a very poor correlation between tumour drug levels and PDT efficacy, with a much better correlation for plasma drug levels.…”

Section: Discussionsupporting

confidence: 92%

“…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%

“…The plasma drug concentrations therefore remain at levels of at least 500 ng ml À1 for up to 96 h after a standard dose of 0.15 mg kg À1 Foscan. This contrasts with the pharmacokinetic profiles in rodents, which demonstrate peak plasma levels within a few minutes of drug administration and a rapid initial clearance, with T 1/2 values of 1 -3 h (Whelpton et al, 1995;Veenhuizen et al, 1997a). In the present study, plasma drug levels were only 1% of the injected dose at 48 h after administration of a 0.3 mg kg À1 Foscan dose.…”

Section: Discussioncontrasting

confidence: 87%

“…Distribution studies in experimental animals have demonstrated that Foscan levels increase in tumours from 1 to 3 days after injection, whereas drug levels in many normal tissues remain constant or decrease over the same period (Alian et al, 1994;Peng et al, 1995;Whelpton et al, 1995Whelpton et al, , 1996Veenhuizen et al, 1997a). This leads to differential drug levels in tumour vs normal tissue at 2 -4 days after injection.…”

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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: 92%

Section: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 87%

mentioning

confidence: 99%

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Foscan® uptake and tissue distribution in relation to photodynamic efficacy

et al. 2003

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“…However, recent animal studies [8,9] and clinical data [10] have shown that the concentration of sensitizer in the tumor at the time of illumination does not necessarily predict response to PDT. Plasma concentration at the time of illumination is a better indicator for PDT outcome [11][12][13][14]. This suggests that tumor cells may not always be direct targets of PDT, but they may be indirectly killed as a result of damage to other cell types, for example, vascular endothelial cells.…”

Section: Working Mechanism Of Pdt In Vivomentioning

confidence: 99%

Photodynamic Therapy in Oncology

Triesscheijn¹,

et al. 2006

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Photodynamic therapy (PDT) is increasingly being recognized as an attractive, alternative treatment modality for superficial cancer. Treatment consists of two relatively simple procedures: the administration of a photosensitive drug and illumination of the tumor to activate the drug. Efficacy is high for small superficial tumors and, except for temporary skin photosensitization, there are no long-term side effects if appropriate protocols are followed. Healing occurs with little or no scarring and the procedure can be repeated without cumulative toxicity. Considering the efficacy and lack of long-term toxicity of PDT, and the fact that the first treatment of cancer with PDT was done more than 100 years ago, one might expect that this treatment had already become an established therapy. However, PDT is currently offered in only a few selected centers, although it is slowly gaining acceptance as an alternative to conventional cancer therapies. Here, we show the developmental steps PDT underwent and summarize the current clinical applications. The data show that, when properly used, PDT is an effective alternative treatment option in oncology. The

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Photodynamic Therapy in the Pleural Space

Baas¹

2006

Thoracic Endoscopy: Advances in Interventional Pulmonology

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Does tumour uptake of Foscan determine PDT efficacy?

Cited by 38 publications

References 14 publications

Foscan® uptake and tissue distribution in relation to photodynamic efficacy

Foscan® uptake and tissue distribution in relation to photodynamic efficacy

Photodynamic Therapy in Oncology

Photodynamic Therapy in the Pleural Space

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