Focal Gene Induction in the Liver of Rats by a Heat-Inducible Promoter Using Focused Ultrasound Hyperthermia

Authors:
  • GDGabriela Divkovic
    Gabriela Divkovic
  • GRGuido Rademaker
    Guido Rademaker
  • NFNabeel Farhan
    Nabeel Farhan
  • PPPeter Peschke
    Peter Peschke
  • IZIvan Zuna
    Ivan Zuna
  • JDJuergen Debus
    Juergen Debus
  • CCClaus D. Claussen
    Claus D. Claussen
  • HKHans-Ulrich Kauczor
    Hans-Ulrich Kauczor
  • CLChuan Yuan Li
    Chuan Yuan Li
  • JJJuergen Jenne
    Juergen Jenne
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Abstract
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). 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). 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°C within the liver parenchyma could be documented. 3 × 109 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. 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.

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