Focal gene induction in the liver of rats by a heat-inducible promoter using focused ultrasound hyperthermia: preliminary results.
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.
Plathow
Christian
C
Department of Radiology, German Cancer Research Center Heidelberg, Germany. c.palthow@dkfz.de
Lohr
Frank
F
Divkovic
Gabriela
G
Rademaker
Guido
G
Farhan
Nabeel
N
Peschke
Peter
P
Zuna
Ivan
I
Debus
Juergen
J
Claussen
Claus D
CD
Kauczor
Hans-Ulrich
HU
Li
Chuan Yuan
CY
Jenne
Juergen
J
Huber
Peter
P
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
D018840:HSP70 Heat-Shock Proteins; D049408:Luminescent Agents; D049452:Green Fluorescent Proteins