Application of 18F-FDG PET for monitoring the therapeutic effect of antiinflammatory drugs on stabilization of vulnerable atherosclerotic plaques.
The rupture of atherosclerotic vulnerable plaques and subsequent formation of thrombi are the main factors responsible for myocardial and cerebral infarctions. Because macrophage infiltration plays an essential role in plaque rupturing, pharmacologic therapy that reduces macrophage infiltration is required to stabilize the vulnerable plaques. The monitoring of therapeutic effect is important in assessing the therapeutic effects of drugs for individual patients. We previously reported that (18)F-FDG accumulates in macrophage-rich plaques. The present study was undertaken to investigate the usefulness of (18)F-FDG PET for monitoring therapies that target vascular inflammation.


METHODS
Myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits were used in this study. The antioxidant probucol was included in the diet fed to 4 rabbits starting at 10 mo of age (probucol group). In a control study, 4 rabbits received standard rabbit chow (control group). (18)F-FDG PET experiments were performed on both groups before the study and at 1, 3, and 6 mo after treatment. After the last imaging session, the rabbits were sacrificed at 3 h after injection of (18)F-FDG, and the aortas were removed. The accumulated radioactivity was then measured, and the number of macrophages was determined by examination of stained sections.


RESULTS
At the age of 10 mo, before the treatment, the aorta could be imaged by (18)F-FDG PET in all rabbits. The aorta could not be imaged after 6 mo of probucol treatment, whereas intense radioactivity was observed in the control rabbits throughout the investigation. The standardized uptake values (SUVs) of the aorta were decreased significantly in the probucol group after 3 mo of intervention as compared with the pretreatment period. The SUVs of the control group were increased gradually at 6 mo. Radioactivity in the aorta was significantly lower in the probucol group than that in the control group. Macrophages were already present at the beginning of the study, and probucol treatment for 6 mo resulted in a significant reduction of macrophage infiltration.


CONCLUSIONS
(18)F-FDG PET was able to image the reduction of inflammation by probucol. (18)F-FDG PET should be useful for evaluating the therapeutic effect of drugs clinically and for the development of new drugs that can stabilize vulnerable plaques. (18)F-FDG PET should be useful for evaluating the therapeutic effect of drugs clinically and for the development of new drugs that can reduce inflammation of vulnerable plaques.
Ogawa
Mikako
M
Laboratory of Genome Bio-Photonics Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Magata
Yasuhiro
Y
Kato
Takashi
T
Hatano
Kentaro
K
Ishino
Seigo
S
Mukai
Takahiro
T
Shiomi
Masashi
M
Ito
Kengo
K
Saji
Hideo
H
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000473:pathology*; D001835:Body Weight; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D011817:Rabbits; D014057:Tomography, X-Ray Computed / Q000379:methods
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D019788:Fluorodeoxyglucose F18