title: In vivo and in vitro evidence that ⁹⁹mTc-HYNIC-interleukin-2 is able to detect T lymphocytes in vulnerable atherosclerotic plaques of the carotid artery.
abstract: OBJECTIVE
  Recent advances in basic science have established that inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Inflammatory cells are thought to be responsible for the transformation of a stable plaque into a vulnerable one. Lymphocytes constitute at least 20 % of infiltrating cells in these vulnerable plaques. Therefore, the interleukin-2 (IL-2) receptor, being overexpressed on activated T lymphocytes, may represent an attractive biomarker for plaque vulnerability. The aim of this study was to evaluate the specificity of radiolabelled IL-2 [(99m)Tc-hydrazinonicotinamide (HYNIC)-IL-2] for imaging the lymphocytic infiltration in carotid plaques in vivo by planar and single photon emission computed tomography (SPECT)/CT imaging and ex vivo by microSPECT and autoradiography.
  
  
  METHODS
  For the in vivo study, ten symptomatic patients with advanced plaques at ultrasound who were scheduled for carotid endarterectomy underwent (99m)Tc-HYNIC-IL-2 scintigraphy. The images were analysed visually on planar and SPECT images and semi-quantitatively on SPECT images by calculating target to background (T/B) ratios. After endarterectomy, immunomorphological evaluation and immunophenotyping were performed on plaque slices. For the ex vivo studies, four additional patients were included and, after in vitro incubation of removed plaques with (99m)Tc-HYNIC-IL-2, autoradiography was performed and microSPECT images were acquired.
  
  
  RESULTS
  Visual analysis defined clear (99m)Tc-HYNIC-IL-2 uptake in seven of the ten symptomatic plaques. SPECT/CT allowed visualization in eight of ten. A significant correlation was found between the number of CD25+ lymphocytes and the total number of CD25+ cells in the plaque and the T/B ratio with adjacent carotid artery as background (Pearson's r = 0.89, p = 0.003 and r = 0.87, p = 0.005, respectively). MicroSPECT imaging showed clear (99m)Tc-HYNIC-IL-2 uptake within the plaque wall and not in the lipidic core. With autoradiography, only CD3+ lymphocytes were found to be labelled.
  
  
  CONCLUSIONS
  These in vivo and ex vivo studies confirm the specificity of (99m)Tc-HYNIC-IL-2 for imaging activated T lymphocytes in carotid plaques. (99m)Tc-HYNIC-IL-2 is a true marker for the inflamed plaque and therefore of plaque instability.
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands, a.w.j.m.glaudemans@umcg.nl.
authors.forename: Andor W J M
authors.initials: AW
authors.lastname: Glaudemans
authors.forename: Elena
authors.initials: E
authors.lastname: Bonanno
authors.forename: Filippo
authors.initials: F
authors.lastname: Galli
authors.forename: Clark J
authors.initials: CJ
authors.lastname: Zeebregts
authors.forename: Erik F J
authors.initials: EF
authors.lastname: de Vries
authors.forename: Michel
authors.initials: M
authors.lastname: Koole
authors.forename: Gert
authors.initials: G
authors.lastname: Luurtsema
authors.forename: Hendrikus H
authors.initials: HH
authors.lastname: Boersma
authors.forename: Maurizio
authors.initials: M
authors.lastname: Taurino
authors.forename: Riemer H J A
authors.initials: RH
authors.lastname: Slart
authors.forename: Alberto
authors.initials: A
authors.lastname: Signore
mesh_terms: D000368:Aged; D001345:Autoradiography; D001692:Biological Transport; D002339:Carotid Arteries / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D015609:Organotechnetium Compounds / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000175:diagnosis* / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000000981:diagnostic imaging* / Q000276:immunology; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: C513398:99mTc-HYNIC-interleukin-12; D015609:Organotechnetium Compounds; D018664:Interleukin-12
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