Effect of rolipram on relative 14C-deoxyglucose uptake in inflammatory lesions and skeletal muscle.
OBJECTIVE
18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has become a useful imaging tool for inflammatory diseases. In this study we investigated the effects of rolipram, a selective phosphodiesterase type 4 inhibitor, on 14C-deoxyglucose (DG) uptake in inflammatory lesions and other normal tissues, and attempted to improve the inflammation/muscle ratio.


METHODS
To induce inflammation, mice were inoculated with turpentine oil. Inflammation-bearing mice were pretreated with rolipram (3 mg/kg i.p. or i.v.), and the effect on 14C-DG uptake was measured using a tissue dissection method and autoradiography. The inflammatory tissue samples were stained with haematoxylin and eosin.


RESULTS
Rolipram (3 mg/kg i.p.) significantly decreased 14C-DG uptake in normal tissues like brain, heart and skeletal muscle (brain 31%, heart 60%, skeletal muscle 61%). On the other hand, 14C-DG uptake in inflammatory lesions was not significantly altered by pretreatment with rolipram. The inflammation/muscle ratio of 14C-DG uptake (30 min after tracer injection) was enhanced from 1.1 to 2.8 by rolipram. An autoradiographic study revealed heterogeneous distributions of 14C-DG in the inflammatory lesions and skeletal muscle of animals that were not treated with rolipram. Pretreatment with rolipram significantly attenuated the intramuscular distribution of 14C-DG, producing a relatively homogeneous distribution of radioactivity.


CONCLUSIONS
These results indicate that rolipram decreased 14C-DG uptake in skeletal muscle by activation of the adenosine 3',5'-cyclic monophosphate system, whereas 14C-DG uptake in inflammatory lesions was not significantly altered. Therefore, rolipram may be a valuable tool for improving the visualisation of inflammatory lesions in clinical PET studies employing FDG.
Shukuri
Miho
M
Department of Medical Physics, School of Allied Health Sciences, Faculty of Medicine, Osaka University, 1-7 Yamadaoka, Suita-shi, Osaka, 565-0871, Japan.
Terai
Masahiro
M
Hosoi
Rie
R
Nishimura
Tsunehiko
T
Gee
Antony
A
Inoue
Osamu
O
D000818:Animals; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D004338:Drug Combinations; D007089:Image Enhancement / Q000379:methods*; D007249:Inflammation / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D020889:Rolipram / Q000008:administration & dosage*; D014425:Turpentine
D004338:Drug Combinations; D010726:Phosphodiesterase Inhibitors; D019275:Radiopharmaceuticals; D003847:Deoxyglucose; D020889:Rolipram; D014425:Turpentine