Purpose/Introduction: Integrins are a family of cell surface heterodimeric glycoproteins that mediate diverse biological events involving cell-cell and cell-matrix interactions. Their expression and function, linked to several pathophysiological processes, is a topic of increasing interest in cardiovascular research. Expression of myocardial avb3 integrin after infarction has already been assessed with different ligands. In this study we used a specific library of cyclic RGD pentapeptide mimic based on azabicycloalkane amino acids that demonstrated high activity and selectivity for integrin avb3 in vitro. This library currently under development by our group, has been conjugated with 68Ga-labelled NOTA derivative thereby enabling it for PET imaging. The goal of this study was to explore by microPET/CT the potential of this RGD scaffold in order to define the time course and the extent of integrin expression in a rat model of myocardial infarction. Subjects & Methods: 5 Rats underwent permanent ligation of the left anterior descending coronary artery and 3 were sham operated. All received intravenous administration of 75 MBq/kg of 68Ga-NOTA-RGD at different times after the operation. Labelling was performed at room temperature with SPE purification; 98% radiochemical purity was checked by HPLC. Micro-PET images were acquired using the YAP-(S)PET scanner; micro-CT images were acquired with the Xalt-HR scanner, that is an engineered small animal CT scanner built in our laboratories. Coregistration between PET and CT images was performed by rigid geometric transformations. ROI for focal tracer uptake were defined on a mid-myocardial section in both ischemic and contro-lateral region of infarcted rats. The ROI definition was the same in sham-operated and infarcted animals. To correlate integrin expression with imaging signals we detected endothelial cells and integrin b3 subunit by CD31 and CD61 immunohistochemical staining in the same hearts. Results: Focal 68Ga-NOTA-RG
68Ga-NOTA cyclic RGD peptide for alphaVbeta3 integrin imaging after myocardial infarction in small animal by PET/CT
Menichetti L;Kusmic C;Panetta D;Pascali G;Petroni D;L'Abbate A;
2010
Abstract
Purpose/Introduction: Integrins are a family of cell surface heterodimeric glycoproteins that mediate diverse biological events involving cell-cell and cell-matrix interactions. Their expression and function, linked to several pathophysiological processes, is a topic of increasing interest in cardiovascular research. Expression of myocardial avb3 integrin after infarction has already been assessed with different ligands. In this study we used a specific library of cyclic RGD pentapeptide mimic based on azabicycloalkane amino acids that demonstrated high activity and selectivity for integrin avb3 in vitro. This library currently under development by our group, has been conjugated with 68Ga-labelled NOTA derivative thereby enabling it for PET imaging. The goal of this study was to explore by microPET/CT the potential of this RGD scaffold in order to define the time course and the extent of integrin expression in a rat model of myocardial infarction. Subjects & Methods: 5 Rats underwent permanent ligation of the left anterior descending coronary artery and 3 were sham operated. All received intravenous administration of 75 MBq/kg of 68Ga-NOTA-RGD at different times after the operation. Labelling was performed at room temperature with SPE purification; 98% radiochemical purity was checked by HPLC. Micro-PET images were acquired using the YAP-(S)PET scanner; micro-CT images were acquired with the Xalt-HR scanner, that is an engineered small animal CT scanner built in our laboratories. Coregistration between PET and CT images was performed by rigid geometric transformations. ROI for focal tracer uptake were defined on a mid-myocardial section in both ischemic and contro-lateral region of infarcted rats. The ROI definition was the same in sham-operated and infarcted animals. To correlate integrin expression with imaging signals we detected endothelial cells and integrin b3 subunit by CD31 and CD61 immunohistochemical staining in the same hearts. Results: Focal 68Ga-NOTA-RGI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
