TY - JOUR
T1 - In vivo and in vitro evidence that Tc-99m-HYNIC-interleukin-2 is able to detect T lymphocytes in vulnerable atherosclerotic plaques of the carotid artery
AU - Glaudemans, Andor W. J. M.
AU - Bonanno, Elena
AU - Galli, Filippo
AU - Zeebregts, Clark J.
AU - de Vries, Erik
AU - Koole, Michel
AU - Luurtsema, Gert
AU - Boersma, Hendrikus H.
AU - Taurino, Maurizio
AU - Slart, Riemer H. J. A.
AU - Signore, Alberto
PY - 2014/9
Y1 - 2014/9
N2 - Purpose 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 [Tc-99m-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 Tc-99m-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 Tc-99m-HYNIC-IL-2, autoradiography was performed and microSPECT images were acquired.Results Visual analysis defined clear Tc-99m-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 Tc-99m-HYNIC-IL-2 uptake within the plaque wall and not in the lipidic core. With autoradiography, only CD3+ lymphocytes were found to be labelled.Conclusion These in vivo and ex vivo studies confirm the specificity of Tc-99m-HYNIC-IL-2 for imaging activated T lymphocytes in carotid plaques. Tc-99m-HYNIC-IL-2 is a true marker for the inflamed plaque and therefore of plaque instability.
AB - Purpose 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 [Tc-99m-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 Tc-99m-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 Tc-99m-HYNIC-IL-2, autoradiography was performed and microSPECT images were acquired.Results Visual analysis defined clear Tc-99m-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 Tc-99m-HYNIC-IL-2 uptake within the plaque wall and not in the lipidic core. With autoradiography, only CD3+ lymphocytes were found to be labelled.Conclusion These in vivo and ex vivo studies confirm the specificity of Tc-99m-HYNIC-IL-2 for imaging activated T lymphocytes in carotid plaques. Tc-99m-HYNIC-IL-2 is a true marker for the inflamed plaque and therefore of plaque instability.
KW - Tc-99m-HYNIC-IL-2
KW - Atherosclerosis
KW - Vulnerable plaque
KW - SPECT/CT
KW - POSITRON-EMISSION-TOMOGRAPHY
KW - TC-99M-INTERLEUKIN-2 SCINTIGRAPHY
KW - TC-99M-LABELED INTERLEUKIN-8
KW - MYOCARDIAL-INFARCTION
KW - ANNEXIN-V
KW - INFLAMMATION
KW - I-123-INTERLEUKIN-2
KW - DISEASE
KW - LESIONS
KW - FLUORODEOXYGLUCOSE
U2 - 10.1007/s00259-014-2764-0
DO - 10.1007/s00259-014-2764-0
M3 - Article
SN - 1619-7070
VL - 41
SP - 1710
EP - 1719
JO - European Journal of Nuclear Medicine and Molecular Imaging
JF - European Journal of Nuclear Medicine and Molecular Imaging
IS - 9
ER -