99mTc-interleukin-2 scintigraphy for the in vivo imaging of vulnerable atherosclerotic plaques
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Several histopathological studies have demonstrated that vulnerable plaques are enriched in inflammatory cells. The aims of this study were: (1a) to test the ability of 99mTc-labelled interleukin-2 (99mTc-IL2) to bind to IL2R-positive (IL2R+) cells in carotid plaques and (1b) to correlate the plaque uptake of 99mTc-IL2, measured in vivo, with the number of IL2R+ cells within the plaque, measured ex vivo by histology (transversal study, TS), and (2) to evaluate changes in 99mTc-IL2 uptake in plaques, before and after treatment with a statin or a hypocholesterolaemic diet (longitudinal study, LS).
Ultrasound scan was performed for plaque characterisation and localisation. Fourteen patients (16 plaques) eligible for endoarterectomy were recruited for the TS and underwent 99mTc-IL2 scintigraphy before surgery. Nine patients (13 plaques) were recruited for the LS; these patients received atorvastatin or a standard hypocholesterolaemic diet and 99mTc-IL2 scintigraphy was performed before and after 3 months of treatment.
The degree of 99mTc-IL2 uptake was expressed as the plaque/background (T/B) ratio. In patients from TS, T/B ratios correlated with the percentage of IL2R+ cells at histology (r=0.707; p=0.002) and the number of IL2R+ cells at flow cytometry (r=0.711; p=0.006). No correlations were observed between ultrasound scores and either scintigraphic or histological findings. In patients from the LS, the mean 99mTc-IL2 uptake decreased in statin-treated patients (1.75±0.50 vs 2.16±0.44; p=0.012), while it was unchanged in the patients on the hypocholesterolaemic diet (2.33±0.45 vs 2.34±0.5).
99mTc-IL2 accumulates in vulnerable carotid plaques; this accumulation is correlated with the amount of IL2R+ cells and is influenced by lipid-lowering treatment with a statin.
KeywordsCarotid arteries Inflammation Interleukin-2 Plaque
This study was partially supported by the Italian Ministry of Public Education, by the International Atomic Energy Agency (IAEA) and by GE-Amersham Healthcare. This paper was awarded with the 2004 Marie Curie award by the European Association of Nuclear Medicine (EANM).
- 4.Muller JE, Stone PH, Turi ZG, Rutherford JD, Czeisler CA, Parker C, et al. Circadian variation in the frequency of onset of acute myocardial infarction. N Engl J Med 1985;13:1315–22Google Scholar
- 12.Iuliano L, Signore A, Violi F. Uptake of oxidized LDL by human atherosclerotic plaque. Circulation 1997;96:2093–4Google Scholar
- 16.Rudd JH, Warburton EA, Fryer TD, Jones HA, Clark JC, Antoun N, et al. Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography (symptomatic, unstable plaques accumulate more 18FDG than asymptomatic lesions). Circulation 2002;105:2708–11CrossRefPubMedGoogle Scholar
- 26.Consensus sur la morphologie et le risque des plaques carotidiennes. A paraître dans Cerebro Vascular Disease. Basel: Karger;1997:N° 3Google Scholar
- 30.North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991;325:445–53Google Scholar
- 31.European Carotid Surgery Trialists’ Collaborative Group. Endarterectomy for moderate symptomatic carotid stenosis: interim results from the MRC European Carotid Surgery Trial. Lancet 1996;347:1591–3Google Scholar