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

基于 mTHPC 的光动力治疗在体内的区间靶向性:效率、药代动力学和细胞凋亡区域分布的相关性

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作者:Julie Garrier, Aude Bressenot, Susanna Gräfe, Sophie Marchal, Soumya Mitra, Thomas H Foster, François Guillemin, Lina Bezdetnaya

Conclusions

The present work suggests that clinical PDT protocols with mTHPC could be greatly improved by fractionation of the drug administration. Time points should be chosen based on the intratumoral spatiotemporal drug distribution.

Purpose

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.

Results

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 of endothelial cells in residual vessels. Concentrations of mTHPC observed in plasma and tumor for the fractionated injection were not statistically different and were less than the total drug dose in each compartment. Conclusions: The present work suggests that clinical PDT protocols with mTHPC could be greatly improved by fractionation of the drug administration. Time points should be chosen based on the intratumoral spatiotemporal drug distribution.

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