title: Pharmacokinetic study of a novel sonosensitizer chlorin-e6 and its sonodynamic anti-cancer activity in hepatoma-22 tumor-bearing mice.
abstract: OBJECTIVE
  The sonodynamically induced anti-tumor effect of chlorin-e6 (Ce6) was studied in mice bearing hepatoma-22 solid tumors.
  
  
  METHODS
  In order to determine the optimum timing of ultrasound exposure after administration of Ce6, the Ce6 concentrations in plasma, skin, muscle and tumor were estimated by measuring the fluorescence intensity of tissue extractions with a fluorescence photometer based on the standard curve. A three-dimensional optical imaging system (IVIS spectrum) was used further to characterize the distribution of Ce6 in H-22 tumor. The anti-tumor effects were estimated by measuring tumor size after sonodynamic therapy.
  
  
  RESULTS
  Similar pharmacokinetic trends of Ce6 in mice were observed either by fluorescence spectrophotometry or by bio-optical imaging. The results also demonstrated that Ce6 has a preferential localization in tumors, but low accumulation and rapid clearance in normal tissues. The results of anti-tumor effects revealed that at an ultrasound intensity of 4 W/cm(2) and a Ce6 dose of ≥10 mg/kg, a significant synergistic effect of ultrasound combined with Ce6 was observed, reducing the tumor volume significantly.
  
  
  CONCLUSIONS
  Chlorin-e6 is a potential sonosensitizer for fluorescence imaging as well as for sonodynamic therapy for cancer. The anti-tumor effect of ultrasound could be enhanced in the presence of Ce6, which might be involved in a sonochemical mechanism.
authors.affiliation: College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Shi
authors.forename: Quanhong
authors.initials: Q
authors.lastname: Liu
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Qin
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D045744:Cell Line, Tumor; D002735:Chlorophyllides; D004353:Drug Evaluation, Preclinical; D005260:Female; D005453:Fluorescence; D006801:Humans; D008113:Liver Neoplasms / Q000628:therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D011166:Porphyrins / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D016896:Treatment Outcome; D014464:Ultrasonic Therapy / Q000379:methods; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D002735:Chlorophyllides; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C062985:phytochlorin