99mTc-interleukin-2 scintigraphy for the in vivo imaging of vulnerable atherosclerotic plaques | springermedicine.com

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European Journal of Nuclear Medicine and Molecular Imaging

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01-02-2006 | Original Article

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

Authors: Alessio Annovazzi, Elena Bonanno, Marcello Arca, Calogero D’Alessandria, Antonella Marcoccia, Luigi G. Spagnoli, Francesco Violi, Francesco Scopinaro, Giorgio De Toma, Alberto Signore

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 2/2006

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Abstract

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 ^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).

Conclusion

^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.

1.

Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med 1999;340:115–26CrossRefPubMed

2.

Schumacher H, Kaiser E, Schnabel PA, Sykora J, Eckstein HH, Allenberg JR. Immunophenotypic characterisation of carotid plaque: increased amount of inflammatory cells as an independent predictor for ischaemic symptoms. Eur J Vasc Endovasc Surg 2001;1:494–501CrossRef

3.

Spagnoli LG, Mauriello A, Sangiorgi G, Fratoni S, Bonanno E, Schwartz RS, et al. Extracranial thrombotically active carotid plaque as a risk factor for ischemic stroke. JAMA 2004;92:1845–52CrossRef

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;13:1315–22

5.

Carr SC, Farb A, Pearce WH, Virmani R, Yao JS. Activated inflammatory cells are associated with plaque rupture in carotid artery stenosis. Surgery 1997;122:757–63CrossRefPubMed

6.

Spagnoli LG, Bonanno E, Mauriello A, Palmieri G, Partenzi A, Sangiorgi G, et al. Multicentric inflammation in epicardial coronary arteries of patients dying of acute myocardial infarction. J Am Coll Cardiol 2002;40:1579–88CrossRefPubMed

7.

Schönbeck U, Mach F, Sukhova GK, Murphy C, Bonnefoy JY, Fabunmi RP, et al. Regulation of matrix metalloproteinase expression in human vascular smooth muscle cells by T lymphocytes: a role for CD40 signaling in plaque rupture? Circ Res 1997;81:448–54PubMed

8.

Yuan C, Tsuruda JS, Beach KN, Hayes CE, Ferguson MS, Alpers CE, et al. Techniques for high resolution MR imaging of atherosclerotic plaque. J Magn Reson Imaging 1994;4:43–9PubMed

9.

Virgolini I, Rauscha F, Lupattelli G, Angelberger P, Ventura A, O’Grady J, et al. Autologous low-density lipoprotein labelling allows characterization of human atherosclerotic lesions in vivo as to presence of foam cells and endothelial coverage. Eur J Nucl Med 1991;18:948–51PubMed

10.

Iuliano L, Signore A, Vallabhajosula S, Colavita AR, Camastra C, Ronga G, et al. Preparation and biodistribution of 99m technetium-labelled oxidized LDL in man. Atherosclerosis 1996;126:131–41CrossRefPubMed

11.

Leitha T, Staudenherz A, Gmeiner B, Hermann M, Huttinger M, Dudczak R. Technetium-99m labelled LDL as a tracer for quantitative LDL scintigraphy. II. In vivo validation, LDL receptor-dependent and unspecific hepatic uptake and scintigraphic results. Eur J Nucl Med 1993;20:674–9PubMed

12.

Iuliano L, Signore A, Violi F. Uptake of oxidized LDL by human atherosclerotic plaque. Circulation 1997;96:2093–4

13.

Ogawa M, Ishino S, Mukai T, Asano D, Teramoto N, Watabe H, et al. ¹⁸F-FDG accumulation in atherosclerotic plaques: immunohistochemical and PET imaging study. J Nucl Med 2004;45:1245–50PubMed

14.

Hanif MZ, Ghesani M, Shah AA, Kasai T. F-18 fluorodeoxyglucose uptake in atherosclerotic plaque in the mediastinum mimicking malignancy: another potential for error. Clin Nucl Med 2004;29:93–5CrossRefPubMed

15.

Tatsumi M, Cohade C, Nakamoto Y, Wahl RL. Fluorodeoxyglucose uptake in the aortic wall at PET/CT: possible finding for active atherosclerosis. Radiology 2003;229:831–7PubMed

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 more¹⁸FDG than asymptomatic lesions). Circulation 2002;105:2708–11CrossRefPubMed

17.

Yun M, Jang S, Cucchiara A, Newberg AB, Alavi A. ¹⁸F FDG uptake in the large arteries: a correlation study with the atherogenic risk factors (cc age/chol and FDG). Semin Nucl Med 2002;32:70–6PubMed

18.

Lederman RJ, Raylman RR, Fisher SJ, Kison PV, San H, Nabel EG, et al. Detection of atherosclerosis using a novel positron-sensitive probe and 18-fluorodeoxyglucose (FDG) (cc SMC/Mac and FDG). Nucl Med Commun 2001;22:747–53CrossRefPubMed

19.

Kolodgie FD, Petrov A, Virmani R, Narula N, Verjans JW, Weber DK, et al. Targeting of apoptotic macrophages and experimental atheroma with radiolabeled annexin V: a technique with potential for noninvasive imaging of vulnerable plaque. Circulation 2003;108:3134–9CrossRefPubMed

20.

Prat L, Torres G, Carrió I, Roca M, Riambau V, Berna L, et al. Polyclonal¹¹¹In-IgG,¹²⁵I-LDL and¹²⁵I-endothelin-1 accumulation in experimental arterial wall injury. Eur J Nucl Med 1993;20:1141–5PubMed

21.

Qin G, Zhang Y, Cao W, An R, Gao Z, Li G, et al. Molecular imaging of atherosclerotic plaques with technetium-99m-labelled antisense oligonucleotides. Eur J Nucl Med Mol Imaging 2005;32:6–14CrossRefPubMed

22.

Knight LC. Non-oncologic applications of radiolabeled peptides in nuclear medicine. Q J Nucl Med 2003;47:279–91PubMed

23.

Robb RJ, Greene WC, Rusk CM. Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen. J Exp Med 1984;160:1126–46CrossRefPubMed

24.

Signore A, Chianelli M, Annovazzi A, Rossi M, Maiuri L, Greco M, et al. Imaging of active lymphocytic infiltration in coeliac disease with ¹²³I-Interleukin-2 and its response to diet. Eur J Nucl Med 2000;27:18–24PubMed

25.

Annovazzi A, Biancone L, Caviglia R, Chianelli M, Capriotti G, Mather SJ, et al. ^99mTc-Interleukin-2 and ^99mTc-HMPAO granulocyte scintigraphy in patients with inactive Crohn’s disease. Eur J Nucl Med Mol Imaging 2003;30:374–82PubMed

26.

Consensus sur la morphologie et le risque des plaques carotidiennes. A paraître dans Cerebro Vascular Disease. Basel: Karger;1997:N° 3

27.

Chianelli M, Signore A, Fritzberg A, Mather SJ. ^99mTc-interleukin-2: the development of technetium-99m labelled Interleukin 2: a new radiopharmaceutical for in vivo detection of mononuclear cell infiltrates in immune mediate diseases. Nucl Med Biol 1997;24:579–86CrossRefPubMed

28.

Bonanno E, Mauriello A, Partenzi A, Anemona L, Spagnoli LG. Flow cytometry analysis of atherosclerotic plaque cells from human carotids: a validation study. Cytometry 2000;39:158–65CrossRefPubMed

29.

Chou ET, Minutello RM, Parikh M, Bergman G, Chiu Wong S, Hong MK. Can we identify vulnerable patients at risk for ST-segment elevation myocardial infarction based on their clinical characteristics? Coron Artery Dis 2004;15:467–69CrossRefPubMed

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;325:445–53

31.

European Carotid Surgery Trialists’ Collaborative Group. Endarterectomy for moderate symptomatic carotid stenosis: interim results from the MRC European Carotid Surgery Trial. Lancet 1996;347:1591–3

32.

Hakonarson H, Kim C, Whelan R, Campbell D, Grunstein MM. Bi-directional activation between human airway smooth muscle cells and T lymphocytes: role in induction of altered airway responsiveness. J Immunol 2001;166:293–303PubMed

33.

Miller DD, Karim MA, Edwards WD, Schwartz RS. Relationship of vascular thrombosis and inflammatory leukocyte infiltration to neointimal growth following porcine coronary artery stent placement. Atherosclerosis 1996;124:145–55CrossRefPubMed

34.

Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J, et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: part I. Circulation 2003;108:1664–72CrossRefPubMed

35.

Sukhova GK, Williams JK, Libby P. Statins reduce inflammation in atheroma of nonhuman primates independent of effects on serum cholesterol. Arterioscler Thromb Vasc Biol 2002;22:1452–8CrossRefPubMed

Title: 99mTc-interleukin-2 scintigraphy for the in vivo imaging of vulnerable atherosclerotic plaques
Authors: Alessio Annovazzi
Elena Bonanno
Marcello Arca
Calogero D’Alessandria
Antonella Marcoccia
Luigi G. Spagnoli
Francesco Violi
Francesco Scopinaro
Giorgio De Toma
Alberto Signore
Publication date: 01-02-2006
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 2/2006
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-005-1899-4

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