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CLINICAL RESEARCH: CARDIAC IMAGING

In Vivo ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography Imaging Provides a Noninvasive Measure of Carotid Plaque Inflammation in Patients

Ahmed Tawakol, MD^_*,_*, Raymond Q. Migrino, MD, Gregory G. Bashian, MD^_*, Shahinaz Bedri, MBBS, David Vermylen, BA^_*, Ricardo C. Cury, MD, Denise Yates, PhD, Glenn M. LaMuraglia, MD^||, Karen Furie, MD, Stuart Houser, MD, Henry Gewirtz, MD^_*, James E. Muller, MD^_*, Thomas J. Brady, MD and Alan J. Fischman, MD, PhD

^_* Departments of Medicine (Cardiac Unit)
Radiology and Nuclear Medicine
Pathology
Neurology
^|| Division of Vascular and Endovascular Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

Manuscript received July 27, 2005; revised manuscript received April 27, 2006, accepted May 2, 2006.

^_* Reprint requests and correspondence: Dr. Ahmed Tawakol, Cardiac Unit/YAW 5904, Massachusetts General Hospital, Boston, Massachusetts 02114. (Email: atawakol{at}partners.org).

OBJECTIVES: Given the importance of inflammation in atherosclerosis, we sought to determine if atherosclerotic plaque inflammation could be measured noninvasively in humans using positron emission tomography (PET).

BACKGROUND: Earlier PET studies using fluorodeoxyglucose (FDG) demonstrated increased FDG uptake in atherosclerotic plaques. Here we tested the ability of FDG-PET to measure carotid plaque inflammation in patients who subsequently underwent carotid endarterectomy (CEA).

METHODS: Seventeen patients with severe carotid stenoses underwent FDG-PET imaging 3 h after FDG administration (13 to 25 mCi), after which carotid plaque FDG uptake was determined as the ratio of plaque to blood activity (target to background ratio, TBR). Less than 1 month after imaging, subjects underwent CEA, after which carotid specimens were processed to identify macrophages (staining with anti-CD68 antibodies).

RESULTS: There was a significant correlation between the PET signal from the carotid plaques and the macrophage staining from the corresponding histologic sections (r = 0.70; p < 0.0001). When mean FDG uptake (mean TBR) was compared with mean inflammation (mean percentage CD68 staining) for each of the 17 patients, the correlation was even stronger (r = 0.85; p < 0.0001). Fluorodeoxyglucose uptake did not correlate with plaque area, plaque thickness, or area of smooth muscle cell staining.

CONCLUSIONS: We established that FDG-PET imaging can be used to assess the severity of inflammation in carotid plaques in patients. If subsequent natural history studies link increased FDG-PET activity in carotid arteries with clinical events, this noninvasive measure could be used to identify a subset of patients with carotid atherosclerosis in need of intensified medical therapy or carotid artery intervention to prevent stroke.

Abbreviations and Acronyms   CEA = carotid endarterectomy   FDG = 18F-fluorodeoxyglucose   hsCRP = high-sensitivity C-reactive protein   PET = positron emission tomography   SUV = standardized uptake value   TBR = target-to-background ratio

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