Application of [¹⁸F]FDG-PET for monitoring the therapeutic effect of anti-inflammatory drug on stabilization of vulnerable atherosclerotic plaques

Abstract

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Objectives: The rupture of atherosclerotic vulnerable plaques and the subsequent formation of thrombi are the main factors responsible for myocardial and cerebral infarctions. Since macrophage infiltration plays an essential role in plaque rupturing, pharmacological therapy that reduces macrophage infiltration is required to stabilize the vulnerable plaque. To monitor the therapeutic effect is important for selecting proper drug for the individual patients. We previously reported that [¹⁸F]FDG accumulates to the macrophage rich plaque^[1]. The present study was undertaken to investigate the usefulness of [¹⁸F]FDG-PET for monitoring the therapies.

Methods: Myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits (WHHLMI rabbits) were used in this study. The anti-inflammatory drug, probucol included diet was fed to four rabbits since 10 months old (probucol group). For control study, four rabbits were received standard rabbit chow (control group). [¹⁸F]FDG-PET experiments were performed before the study, and 1, 3 and 6 months after the treatments in both groups. After the last imaging, the rabbits were sacrificed at 3 hour post-injection of [¹⁸F]FDG, and the aortas were removed. Then the accumulated radioactivity was measured, and the numbers of macrophages were investigated by examination of stained sections.

Results: At the age of 10 months, before the treatment, the aorta could be imaged by [¹⁸F]FDG-PET in all rabbits. The aorta could not be imaged after the 6 months of probucol treatment, while intense radioactivity was observed in the control rabbits throughout the investigation. The SUVs of the aorta were significantly decreased in the probucol group after 3 months of intervention compared to the pre treatment period. The SUVs of the control group were gradually increased in 6 months. The radioactivity in the removed aorta was significantly lower in the probucol group than that in the control group. Probucol treatment for 6 months resulted in a significant diminution of macrophage infiltration.

Conclusions: [¹⁸F]FDG-PET could image the passage of plaque stabilizing by probucol, that is, decrease of macrophage infiltration. [¹⁸F]FDG-PET should be useful to evaluate the therapeutic effect of drugs clinically and be available for developing new drugs that can stabilize the vulnerable plaque. [1] Ogawa M, et al. JNM 45:1245-1250 (2004).