Abstract 2332: A Novel Nanoparticle for PET-CT Imaging of Inflammatory Atherosclerotis
Monocytes/Macrophages (Mac) are recognized as a main cellular player in inflammatory atherosclerosis and avidly ingest dextran coated magnetic nanoparticles (CLIO, sensed by MRI). In order to expand the cellular specificity to other imaging modalities and to perform cross-platform validation, we developed a PET detectable magnetofluorescent nanoparticle (CLIO-Cu64-VT680). This study investigates the value of CLIO-Cu64-VT680 for imaging of inflammatory atherosclerosis. In 5 apoE−/− mice, iodine enhanced PET-CT imaging was performed 24hr after injection of CLIO-Cu64-VT680 during isoflurane anesthesia. Following PET-CT, excised aortas were analyzed by scintillation counting and autoradiography. Fluorescence and immunoreactive microscopy and was subsequently performed. Peak PET activity mapped to areas of high plaque load identified by CT, such as the aortic root and arch (Figure⇓). % injected dose in apoE−/− aortas was 260% and in carotids 392% of respective wild type organs (p<.05). Autoradiography corroborated in-vivo findings (Figure⇓). Half life of CLIO-Cu64-VT680 was 259min. Imaging findings correlated with fluorescence microscopy, which demonstrated preferential uptake of CLIO-Cu64-VT680 into Mac (MAC-3, 21+/−7 cells/high power field), and lower uptake in surrounding smooth muscle and endothelial cells (alpha actin, 4+/−2; CD31, 4+/−2, p<.05). In conclusion, we here report on the capability of a novel tri-modality nanoparticle to detect Mac distribution in atherosclerotic plaques. Advantages include maximized sensitivity, potential whole body imaging, quantification of the PET signal and spatial localization of tri-reporter by microscopy.