title: Optimal treatment opportunity for mTHPC-mediated photodynamic therapy of liver cancer.
abstract: Photodynamic therapy (PDT) has been clinically used for liver cancer. The pharmacokinetics of a photosensitizer needs to be monitored so that PDT can be performed at the most favorable time and with the proper dose to increase the cure rate. As mTHPC is a fluorescent compound, we investigate its pharmacokinetics, distribution, and elimination in the rat orthotropic liver cancer model in order to confirm an optimal treatment opportunity of liver cancer PDT. After intravenous administration at a single dose of 300 μg/kg, mTHPC was extracted from tissue homogenates or plasma. Then, mTHPC concentrations were assessed by fluorescence spectroscopy and the data were processed with PK-GRAPH pharmacokinetic procedure. The plasma concentration-time profile of mTHPC showed a short distribution half-life (T½α = 0.082 h) and a relatively longer elimination half-life (T½β = 28.23 h), which quite fitted with a two-compartment model. The results of mTHPC tissue distributions showed that the highest drug accumulation was in tumor tissue, and successively decreased in liver, heart, spleen, muscle, and skin tissues. The drug distribution ratio of tumor to normal tissue reached the peak at 24 h after mTHPC administration. mTHPC was eliminated at a suitable rate in rat orthotropic liver cancer model, and there was no long-term accumulation of mTHPC in rat tissues. For PDT of orthotropic liver cancer, 24 h after mTHPC intravenous injection may be the optimal treatment time point, which might provide higher clinical efficacy and reduce side effects.
authors: Department of General Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, No. 1665, Kongjiang Road, Shanghai, 200092, China.
authors: Jian-dong
authors: JD
authors: Wang
authors: Jun
authors: J
authors: Shen
authors: Xue-ping
authors: XP
authors: Zhou
authors: Wei-bin
authors: WB
authors: Shi
authors: Jiang-hua
authors: JH
authors: Yan
authors: Fang-hong
authors: FH
authors: Luo
authors: Zhi-wei
authors: ZW
authors: Quan
mesh_terms: D000818:Animals; D002279:Carcinoma 256, Walker / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D006207:Half-Life; D007275:Injections, Intravenous; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008652:Mesoporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence; D014018:Tissue Distribution
chemical_list: D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin
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