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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Annovazzi
Alessio
A
Nuclear Medicine, 2nd Faculty of Medicine, University La Sapienza, Rome, Italy.
Bonanno
Elena
E
Arca
Marcello
M
D'Alessandria
Calogero
C
Marcoccia
Antonella
A
Spagnoli
Luigi G
LG
Violi
Francesco
F
Scopinaro
Francesco
F
De Toma
Giorgio
G
Signore
Alberto
A
D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000175:diagnosis* / Q000178:diet therapy / Q000188:drug therapy / Q000378:metabolism*; D000069059:Atorvastatin; D002339:Carotid Arteries / Q000473:pathology; D004036:Diet, Atherogenic; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007249:Inflammation / Q000175:diagnosis / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology; D011877:Radionuclide Imaging / Q000295:instrumentation / Q000379:methods*; D013667:Technetium
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007376:Interleukin-2; D011758:Pyrroles; D013667:Technetium; D000069059:Atorvastatin