talaporfin and temoporfin

What is the current status of photodynamic therapy (PDT) with regard to treating malignant brain tumors? Despite several decades of effort, PDT has yet to achieve standard of care.. The questions we wish to answer are: where are we clinically with PDT, why is it not standard of care, and what is being done in clinical trials to get us there.. Rather than a meta-analysis or comprehensive review, our review focuses on who the major research groups are, what their approaches to the problem are, and how their results compare to standard of care. Secondary questions include what the effective depth of light penetration is, and how deep can we expect to kill tumor cells.. A measurable degree of necrosis is seen to a depth of about 5mm. Cavitary PDT with hematoporphyrin derivative (HpD) results are encouraging, but need an adequate Phase III trial. Talaporfin with cavitary light application appears promising, although only a small case series has been reported. Foscan for fluorescence guided resection (FGR) plus intraoperative cavitary PDT results were improved over controls, but are poor compared to other groups. 5-Aminolevulinic acid-FGR plus postop cavitary HpD PDT show improvement over controls, but the comparison to standard of care is still poor.. Continued research in PDT will determine whether the advances shown will mitigate morbidity and mortality, but certainly the potential for this modality to revolutionize the treatment of brain tumors remains. The various uses for PDT in clinical practice should be pursued.

Topics: Aminolevulinic Acid; Brain Neoplasms; Cell Death; Clinical Trials as Topic; Fluorescence; Hematoporphyrin Derivative; Humans; Infratentorial Neoplasms; Mesoporphyrins; Nitric Oxide; Photochemotherapy; Photosensitizing Agents; Porphyrins; Signal Transduction; Surgery, Computer-Assisted

Recent studies have demonstrated an effect of photodamage on the endocytic pathway involved in recycling of membrane components. Using a series of agents with known sub-cellular targets, we explored the determinants of photodynamic inhibition of endocytic processes in three cell lines: A murine leukemia, a murine hepatoma, and a non-malignant epithelial cell line of human origin.. The PI-3 kinase antagonist wortmannin blocks endosomal processing pathway dependent on this enzyme, providing an indication of the "flux" of endocytosis. Microscopic observations were used to assess the effect of photodamage on this pathway. Photosensitizing agents specific for mitochondrial, endoplasmic reticulum (ER), lysosomal, and endosomal photodamage were employed.. Sub-lethal photodamage directed against endosomes or lysosomes interrupted early steps in this endocytic process in the hepatoma cell line. A mechanism for these effects is proposed. Mitochondrial photodamage could interrupt endocytosis, but at levels that also induced apoptosis. ER photodamage did not affect endocytosis even at lethal levels. Somewhat similar results were obtained with other cell lines, but there were sufficient differences to indicate that the cell phenotype is, in part, a determinant of the endocytic response to PDT.. PDT is therefore seen to have an effect on endocytic processes. Further work will be needed to delineate the role of these endocytic effects in the array of responses to photodynamic therapy.

Topics: Androstadienes; Animals; Carcinoma, Hepatocellular; Cell Line; Cell Line, Tumor; Endocytosis; Epithelial Cells; Humans; Indoles; Leukemia; Liver Neoplasms; Mesoporphyrins; Mice; Models, Biological; Organelles; Organometallic Compounds; Phosphodiesterase Inhibitors; Photochemotherapy; Photosensitizing Agents; Porphyrins; Wortmannin

New photosensitizing drugs are becoming available which should improve on some of the disadvantages of haematoporphyrin derivates for photodynamic therapy (PDT). The main features are shorter duration of systemic photosensitisation, activation by longer and more penetrating light and better tumour to normal tissue drug uptake ratios. These drugs together with better understanding of in vivo light dosimetry promise to improve both results and clinical acceptability for PDT in future studies.

Topics: Aminolevulinic Acid; Forecasting; Humans; Indoles; Isoindoles; Mesoporphyrins; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Porphyrins; Zinc Compounds