The pharmacokinetic behavior of the photosensitizer meso-tetra-hydroxyphenyl-chlorin in mice and men.

Purpose: Meso-tetra-hydroxyphenyl-chlorin (mTHPC) is a hydrophobic photosensitizer that binds to plasma lipoproteins after intravenous injection. In vitro experiments with human plasma have shown that mTHPC initially binds to an unknown protein and subsequently redistributes to lipoprotein fractions. It has been suggested that this might explain the unusual pharmacokinetic profile of mTHPC humans.

Optimizing meso-tetra-hydroxyphenyl-chlorin-mediated photodynamic therapy for basal cell carcinoma.

Meso-tetra-hydroxyphenyl-chlorin (mTHPC)-mediated photodynamic therapy (PDT) has shown to be effective in the treatment of patients with multiple basal cell carcinoma (BCC). In the present study we further optimized the drug-light interval and examined the correlation between plasma drug levels and treatment efficacy. Thirteen patients with multiple BCC (a total of 366 lesions) were included in the study.

Doppler optical coherence tomography to monitor the effect of photodynamic therapy on tissue morphology and perfusion.

We investigated the feasibility of using optical coherence tomography (OCT) for noninvasive real-time visualization of the vascular effects of photodynamic therapy (PDT) in normal and tumor tissue in mice. Perfusion control measurements were initially performed after administrating vaso-active drugs or clamping of the subcutaneous tumors. Subsequent measurements were made on tumor-bearing mice before and after PDT using the photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC).

Outcome of mTHPC mediated photodynamic therapy is primarily determined by the vascular response.

We have previously shown that the efficacy of photodynamic therapy (PDT) using the photosensitizer meso-tetra-hydroxyphenyl-chlorin (mTHPC) correlated with plasma drug levels at the time of illumination rather than drug levels in human tumor xenografts or mouse skin. These results suggested that vascular-mediated effects could be important determinants of PDT response in vivo. In the present study we further investigated the relationship between PDT response, mTHPC pharmacokinetics and the localization and extent of vascular damage induced in human squamous cell carcinoma xenografts (HNXOE).

Comparative sensitivity of microvascular endothelial cells, fibroblasts and tumor cells after in vitro photodynamic therapy with meso-tetra-hydroxyphenyl-chlorin.

The phototoxic effect of meso-tetra-hydroxyphenyl-chlorin (mTHPC)-mediated photodynamic therapy (PDT) on human microvascular endothelial cells (hMVEC) was compared with that on human fibroblasts (BCT-27) and two human tumor cell lines (HMESO-1 and HNXOE). To examine the relationship between intrinsic phototoxicity and intracellular mTHPC content, we expressed cell survival as a function of cellular fluorescence. On the basis of total cell fluorescence, HNXOE tumor cells were the most sensitive and BCT-27 fibroblasts the most resistant, but these differences disappeared after correcting for cell volume.

Meta-tetra(hydroxyphenyl)chlorin photodynamic therapy in early-stage squamous cell carcinoma of the head and neck.

Objective: Photodynamic therapy (PDT) is a relatively new treatment modality for various types of cancer, including cancer of the head and neck. The advent of the second-generation photosensitizers such as meta-tetra(hydroxyphenyl)chlorin (mTHPC) (Foscan; Scotia Pharmaceuticals, Stirling, Scotland), which are more effective and less phototoxic to the skin than their forerunners, now makes this treatment a feasible alternative to surgery or radiotherapy in specific cases. To evaluate the long-term outcome of this therapy for squamous cell carcinomas of the head and neck, we treated patients with PDT using mTHPC.

Oxygen depletion during and after mTHPC-mediated photodynamic therapy in RIF1 and H-MESO1 tumors.

During photodynamic therapy (PDT), low oxygenation levels, induced both by oxygen consumption and by vascular occlusion, can lead to an inefficient photochemical reaction that may compromise the efficacy of PDT. In the present studies, tumor oxygenation was measured before, during and after meta-tetrahydroxyphenylchlorin (mTHPC)-mediated PDT of murine RIF1 tumors and human mesothelioma xenografts (H-MESO1). Tumor pO2 was measured in real time with Eppendorf polarography, and the extent of relative hypoxia at specific times was measured by immunohistochemical staining.