Comparison of the photobleaching effect of three photosensitizing agents: Meso-tetra(m-hydroxyphenyl)chlorin, meso-tetra(m-hydroxyphenyl)porphyrin and photofrin during photodynamic therapy

W., L.; Moan, Johan Emelian; Berg, Kristian

doi:10.1007/bf02590361

Cited by 49 publications

(37 citation statements)

References 16 publications

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“…It is also clear that there is a threshold (of both light and drug dose) for PDT effect (Bown et al, 1986;Van Gemert et al, 1985), and this threshold may be higher for normal tissue than for tumour. Photobleaching, which is known to be substantial for mTHPC (Ma et al, 1994), may play an important role in keeping drug levels below the threshold value and helping to selectively spare the normal tissue. These factors may all contribute to successful mTHPC-mediated PDT.…”

Section: Discussionmentioning

confidence: 99%

Does tumour uptake of Foscan determine PDT efficacy?

et al. 1997

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Section: Discussionmentioning

confidence: 99%

Does tumour uptake of Foscan determine PDT efficacy?

et al. 1997

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“…This is in agreement with studies in the mouse (Cramers et al, 2003). This m-THPC could give rise to prolonged skin sensitivity although it may be rapidly photobleached, due to the sharp absorption bands, avoiding the photosensitivity (Ma et al, 1994). Studies in the hamster (Blant et al, 2002) have shown that levels of m-THPC in striated muscle are very low, increasing slightly over 200 h. This was shown to be quite different from smooth muscle, which accumulated relatively higher levels and peaked at about 36 h. The data for striated muscle in the BDIX rat presented here are consistent with the data for the hamster model.…”

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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“…Photodegradation of mTHPC in solution, in vitro and in vivo, has been well documented (Ma et al, 1994b;Belitchenko et al, 1998;Rezzoug et al, 1998). Reducing agents can modulate photosensitizer photobleaching (Spikes, 1992).…”

Section: Discussionmentioning

confidence: 99%