title: An in-vivo investigation of the therapeutic effect of pulsed focused ultrasound on tumor growth.
abstract: OBJECTIVE
  High-intensity focused ultrasound (HIFU) has been investigated for ablative therapy and drug enhancement for gene therapy and chemotherapy. The aim of this work is to explore the feasibility of pulsed focused ultrasound (pFUS) for cancer therapy using an in vivo animal model.
  
  
  METHODS
  A clinical HIFU system (InSightec ExAblate 2000) integrated with a 1.5 T GE MR scanner was used in this study. Suitable ultrasound parameters were investigated to perform nonthermal sonications, keeping the temperature elevation below 4 °C as measured in real time by MR thermometry. LNCaP cells (10(6)) were injected into the prostates of male mice (n = 20). When tumors reached a diameter of about 5 mm in 3D as measured on magnetic resonance imaging (MRI), the tumor-bearing mice (n = 8) were treated with pFUS (1 MHz frequency; 25 W acoustic power; 0.1 duty cycle; 60 s duration). A total of 4-6 sonications were used to cover the entire tumor volume under MR image guidance. The animals were allowed to survive for 4 weeks after the treatment. The tumor growth was monitored on high-resolution (0.2 mm) MRI weekly post treatment and was compared with that of the control group (n = 12).
  
  
  RESULTS
  Significant tumor growth delay was observed in the tumor-bearing mice treated with pFUS. The mean tumor volume for the pFUS treated mice remained the same 1 week after the treatment while the mean tumor volume of the control mice grew 42% over the same time. Two weeks after the pFUS treatment, the control group had a mean tumor volume 40% greater than that of the treated group. There was a greater variation in tumor volume at 4 weeks post treatment for both treated and control mice and a slightly faster tumor growth for the pFUS treated mice.
  
  
  CONCLUSIONS
  The authors' results demonstrated that pFUS may have a great potential for cancer therapy. Further experiments are warranted to understand the predominantly nonthermal cell killing mechanisms of pFUS and to derive optimal ultrasound parameters and fractionation schemes to maximize the therapeutic effect of pFUS.
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
authors.forename: C-M
authors.initials: CM
authors.lastname: Ma
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
authors.forename: Dusica
authors.initials: D
authors.lastname: Cvetkovic
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
authors.forename: Lili
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D055592:Biophysical Phenomena; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D053148:Caspase 3; D006657:Histones; C505409:Casp3 protein, mouse; C475961:gamma-H2AX protein, mouse