title: Study of the mechanism of sonodynamic therapy in a rat glioma model.
abstract: OBJECTIVE
  The study reported here examined the effect of hematoporphyrin monomethyl ether (HMME)-mediated sonodynamic therapy (SDT) on C6 gliomas implanted in rat brains.
  
  
  METHODS
  Two weeks after inoculation, glioma development was evaluated by measuring tumor volume using a 1.5 T magnetic resonance imager. Rats that had a well-developed C6 glioma (usually when the tumor diameter reached 3-5 mm) were used to test SDT, ultrasound-alone, and HMME-alone treatments. Rats both administered and not administered intravenous HMME 10 μg/mL were insonated by a 1 MHz ultrasound at a dose of 0.5 W/cm(2).
  
  
  RESULTS
  SDT treatment could effectively inhibit the expansion of intracranial gliomas in vivo. The treatment with ultrasound alone could inhibit glioma growth within 1 week; however, 1 week later, the tumor started growing again. In contrast, the effect of SDT could last at least 2 weeks. Injection of HMME alone had no effects on inhibiting glioma growth, suggesting the sonosensitizer HMME has no antitumor effect. Both SDT and ultrasound-alone treatment could extend the survival of rats implanted with a C6 glioma. Pathological and electron microscopic examinations suggested SDT and ultrasound-alone treatment could induce glioma necrosis by way of triggering glioma-cell apoptosis, which was confirmed by immunohistological examination with cytochrome-c and caspase-3 antibodies. Most importantly, we found that the sonosensitizer HMME could enhance the ultrasound-induced antitumor effect by selectively assisting ultrasound targeting of glioma angiogenesis inhibition.
  
  
  CONCLUSIONS
  This study with a rat C6 glioma experimental model showed that SDT can potentially be useful in the treatment of deep-seated malignant gliomas.
authors.affiliation: Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai Fengxian District Central Hospital, Shanghai, People's Republic of China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Song
authors.affiliation: Department of Neurosurgery, The Fourth College Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Wu
authors.initials: W
authors.lastname: Yue
authors.affiliation: Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai Fengxian District Central Hospital, Shanghai, People's Republic of China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Fourth College Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai Fengxian District Central Hospital, Shanghai, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai Fengxian District Central Hospital, Shanghai, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
keywords: antitumor mechanism; hematoporphyrin monomethyl ether; ultrasound