Long circulating half-life and high tumor selectivity of the photosensitizer meta-tetrahydroxyphenylchlorin conjugated to polyethylene glycol in nude mice grafted with a human colon carcinoma
| Autor: | Daniel Braichotte, P. Westermann, Georges Wagnières, M. Forrer, Jean-Pierre Mach, Snezana Andrejevic, Hubert van den Bergh, Philippe Monnier, S. Folli, Thomas Glanzmann |
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| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Biodistribution BPR (Biological process) medicine.medical_treatment Photodynamic therapy BIOL (Biological study) Polyethylene glycol except adverse) unclassified) chemistry.chemical_compound In vivo PEG ratio medicine Fluorescence microscope Photosensitizer 122341-38-2D Role: BAC (Biological activity or effector BSU (Biological study business.industry mTHPC PEG conjugate photosensitizer tumor uptake Molecular biology Oncology chemistry PROC (Process) THU (Therapeutic use) USES (Uses) (circulating half-life and tumor select business Conjugate |
| Popis: | In a mode of nude mice bearing a human colon carcinoma xenograft, the biodistribution and tumor localization of metatetrahydroxyphenylchlorin (m-THPC) coupled to polyethylene glycol (PEG) were compared with those of the free form of this photosensitizer used in photodynamic therapy (PDT). At different times after i.v. injection of both forms of 125I-labeled photosensitizer, m-THPC-PEG gave on average a 2-fold higher tumor uptake than free m-THPC. In addition, at early times after injection, m-THPC-PEG showed a 2-fold longer blood circulating half-life and a 4-fold lower liver uptake than free m-THPC. The tumor to normal tissue ratios of radioactivity concentrations were always higher for m-THPC-PEG than for free m-THPC at any time point studied from 2 to 96 hr post-injection. Significant coefficients of correlation between direct fluorescence measurements and radioactivity counting were obtained within each organ tested. Fluorescence microscopy studies showed that m-THPC-PEG was preferentially localized near the tumor vessels, whereas m-THPC was more diffusely distributed inside the tumor tissue. To verify whether m-THPC-PEG conjugate remained phototoxic in vivo, PDT experiments were performed 72 hr after injection and showed that m-THPC-PEG was as potent as free m-THPC in the induction of tumor regression provided that the irradiation does for m-THPC-PEG conjugate was adapted to a well-tolerated 2-fold higher level. The overall results demonstrate first the possibility of improving the in vivo tumor localization of a hydrophobic dye used for PDT by coupling it to PEG and second that a photosensitizer conjugated to a macromolecule can remain phototoxic in vivo. |
| Databáze: | OpenAIRE |
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