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BACKGROUND: This study aimed to determine if delayed (18)F-fluorodeoxyglucose ((18)FDG) PET/CT imaging improves quantitation of atherosclerotic plaque inflammation. Blood-pool activity can disturb the arterial (18)FDG signal. With time, blood-pool activity declines. Therefore, delayed imaging can potentially improve quantitation of vascular inflammation.METHODS AND RESULTS: 40 subjects were prospectively assessed by dual-time-point PET/CT imaging at approximately 90 and 180 minutes after (18)FDG administration. For both time-points, global uptake of (18)FDG was determined in the carotid arteries and thoracic aorta by calculating the blood-pool corrected maximum standardized uptake value (cSUVMAX). A target-to-background ratio (TBR) was calculated to determine the contrast resolution at 90 and 180 minutes. Furthermore, we assessed whether the acquisition time-point affected the relation between cSUVMAX and the estimated 10-year risk for fatal cardiovascular disease (SCORE %). A significant increase in carotid cSUVMAX (23%, P < .0001), carotid TBR (20%, P < .0001), aortic cSUVMAX (14%, P < .0001), and aortic TBR (20%, P < .0001) was observed with time. At 90 minutes, cSUVMAX did not relate to SCORE %, whereas at 180 minutes significant positive relations were observed between SCORE % and carotid (τ = 0.25, P = .045) and aortic (τ = 0.33, P = .008) cSUVMAX.CONCLUSIONS: Delayed (18)FDG PET/CT imaging at 180 minutes improves quantitation of atherosclerotic plaque inflammation over imaging at 90 minutes. Therefore, the optimal acquisition time-point to assess atherosclerotic plaque inflammation lies beyond the advocated time-point of 90 minutes after (18)FDG administration.