Compartmental targeting for mTHPC-based photodynamic treatment in vivo: Correlation of efficiency, pharmacokinetics, and regional distribution of apoptosis.

International Journal of Radiation Oncology, Biology, Physics
Julie GarrierLina Bezdetnaya

Abstract

The present study investigates the efficacy of compartmental targeting in xenografted tumors treated by meta-tetra(hydroxyphenyl)chlorin (mTHPC)-mediated photodynamic therapy (PDT). The therapeutic efficacy was, furthermore, related to a regional photoinduced distribution of apoptosis and an mTHPC biodistribution profile. Mice bearing EMT6 tumors were subjected to a single irradiation (10 J/cm(2)) of red laser light (652 nm) at different intervals after a single- (0.3 mg/kg or 0.15 mg/kg) or double-intravenous (2 × 0.15 mg/kg) injection(s) of mTHPC. Efficiency of the treatment was evaluated by monitoring tumor regrowth. mTHPC pharmacokinetics were assessed by high-performance liquid chromatography analysis of excised organs. The regional distribution of apoptosis in tumor sections was investigated with a newly developed colabelling immunohistochemistry technique. A fractionated double-injection protocol of mTHPC with 24-h and 3-h drug-light intervals (DLI) yielded 100% tumor cure, with tumors presenting a massive apoptosis of neoplastic cells along with a distortion of vessels. The best efficiency for a single injection (0.3 mg/kg) was about 54% tumor cure and corresponded to a DLI of 3 h. At this DLI, tumors showed apoptosis o...Continue Reading

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Citations

Feb 5, 2013·Lasers in Medical Science·Jian-dong WangZhi-wei Quan
Aug 19, 2011·Photochemistry and Photobiology·Mathias O Senge, Johan C Brandt
Jan 29, 2013·The Journal of Urology·Aurélie FrançoisMarie Ange D'Hallewin
Nov 22, 2011·The Journal of Urology·Stephanie G C KroezeJudith J M Jans
Jan 8, 2015·Lasers in Medical Science·Sophie MarchalLina Bezdetnaya
Oct 11, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Melissa J BovisAlexander J Macrobert
Jul 26, 2016·Biomedical Optics Express·Katja HaedickeIngrid Hilger

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