Focal gene induction in the liver of rats by a heat-inducible promoter using focused ultrasound hyperthermia: preliminary results

Invest Radiol. 2005 Nov;40(11):729-35. doi: 10.1097/01.rli.0000184763.62578.06.

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).

Materials and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Gene Expression Regulation*
  • Genetic Therapy
  • Genetic Vectors
  • Green Fluorescent Proteins
  • HSP70 Heat-Shock Proteins / genetics*
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat-Shock Response / genetics*
  • Hepatocytes / metabolism*
  • Hyperthermia, Induced / methods*
  • Liver / diagnostic imaging*
  • Luminescent Agents
  • Magnetic Resonance Imaging
  • Male
  • Microscopy, Fluorescence
  • Models, Animal
  • Promoter Regions, Genetic
  • Rats
  • Rats, Inbred Strains
  • Transcriptional Activation
  • Transgenes / physiology
  • Ultrasonography

Substances

  • HSP70 Heat-Shock Proteins
  • Luminescent Agents
  • Green Fluorescent Proteins