99mTc-interleukin-2 scintigraphy for the in vivo imaging of vulnerable atherosclerotic plaques

Purpose: 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 Tc-99m-labelled interleukin-2 (Tc-99m-IL2) to bind to IL2R-positive (IL2R+) cells in carotid plaques and (1b) to correlate the plaque uptake of Tc-99m-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 Tc-99m-IL2 uptake in plaques, before and after treatment with a statin or a hypocholesterolaemic diet ( longitudinal study, LS). Methods: Ultrasound scan was performed for plaque characterisation and localisation. Fourteen patients ( 16 plaques) eligible for endoarterectomy were recruited for the TS and underwent Tc-99m-IL2 scintigraphy before surgery. Nine patients ( 13 plaques) were recruited for the LS; these patients received atorvastatin or a standard hypocholesterolaemic diet and Tc-99m-IL2 scintigraphy was performed before and after 3 months of treatment. Results: The degree of Tc-99m-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 Tc-99m-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). Conclusion: Tc-99m-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.