title: Focal gene induction in the liver of rats by a heat-inducible promoter using focused ultrasound hyperthermia: preliminary results.
abstract: OBJECTIVE
  We sought to examine high-intensity focused ultrasound (HIFU)-induced hyperthermia in the liver of a rat model to focally induce green-fluorescent protein (GFP).
  
  
  METHODS
  A total of 25 Copenhagen rats were included in this study. Rats were divided into groups treated with an adenovirus coding for green fluorescent protein (GFP) under the control of a hsp70B promoter and a CMV promoter. Ad-CMV-GFP-treated rats served as positive control. Untreated controls only subjected to MRI +/- HIFU-treatment served to find out optimal power of HIFU in the target area of the liver. Temperature was noninvasively monitored by temperature sensitive magnetic resonance imaging (MRI).
  
  
  RESULTS
  Rats treated with Ad-hsp70B-GFP demonstrated localized gene induction within the liver parenchyma, in good correlation with MRI and histology. Applying an acoustic power of 1.92 W a relatively uniform focal temperature up to 42 +/- 5 degrees C within the liver parenchyma could be documented. 3 x 10(9) plaque-forming units proved to account for a very homogeneous liver infection. Number of fluorescent cells in the region of hyperthermia was similar to the control group treated with Ad-CMV-GFP.
  
  
  CONCLUSIONS
  Using the introduced parameters spatially controlled gene induction within a parenchymal organ such as the liver in rats using HIFU under control of MRI is feasible.
authors.affiliation: Department of Radiology, German Cancer Research Center Heidelberg, Germany. c.palthow@dkfz.de
authors.forename: Christian
authors.initials: C
authors.lastname: Plathow
authors.forename: Frank
authors.initials: F
authors.lastname: Lohr
authors.forename: Gabriela
authors.initials: G
authors.lastname: Divkovic
authors.forename: Guido
authors.initials: G
authors.lastname: Rademaker
authors.forename: Nabeel
authors.initials: N
authors.lastname: Farhan
authors.forename: Peter
authors.initials: P
authors.lastname: Peschke
authors.forename: Ivan
authors.initials: I
authors.lastname: Zuna
authors.forename: Juergen
authors.initials: J
authors.lastname: Debus
authors.forename: Claus D
authors.initials: CD
authors.lastname: Claussen
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Kauczor
authors.forename: Chuan Yuan
authors.initials: CY
authors.lastname: Li
authors.forename: Juergen
authors.initials: J
authors.lastname: Jenne
authors.forename: Peter
authors.initials: P
authors.lastname: Huber
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D018869:Heat-Shock Response / Q000235:genetics*; D022781:Hepatocytes / Q000378:metabolism*; D006979:Hyperthermia, Induced / Q000379:methods*; D008099:Liver / Q000000981:diagnostic imaging*; D049408:Luminescent Agents; D008279:Magnetic Resonance Imaging; D008297:Male; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D011401:Promoter Regions, Genetic; D051381:Rats; D011919:Rats, Inbred Strains; D015533:Transcriptional Activation; D019076:Transgenes / Q000502:physiology; D014463:Ultrasonography
chemical_list: D018840:HSP70 Heat-Shock Proteins; D049408:Luminescent Agents; D049452:Green Fluorescent Proteins