Radiolabeled Iron Oxide Nanoparticles
Magnetic properties of iron oxide nanoparticles render them as an ideal candidate for MRI, PET, and SPECT imaging technologies [69—71]. Lee et al. prepared radiolabeled iron oxide nanoparticle conjugated to a RGD peptide (arginine, glycine, aspartic acid) functionalized with (1,4,7,10-tetraazacyclododecane)-1,4,7,10-tetraacetate (DOTA) (chelator) for labeling with 64Cu. Mice bearing human glioblastoma exhibited the highest uptake at the tumor site at 4 h after injection. The specificity of this construct was examined by blocking RGD receptors, avb3 integrin, with unconjugated nanoparticles [72].
A trifunctional modality comprising PET/near-infrared fluorescence (NIRF)/MRI functional iron oxide nanoparticles has been reported by Xie et al. This study documented that 64Cu-DOTA and Cy 5.5 CLIO (cross-linked iron oxide nanoparticles) were injected into a sub-cutaneous xenograft U87MG tumor-bearing mice. Delineation of tumors was reported in all three modalities. However, PET imaging revealed high muscle to tumor ratio relative to NIRF results [73]. Nahrendorf et al. studied dextranated DTPA-modified magnetofluorescent 20-nm nanoparticles. These particles with 64Cu radionuclide were injected into ApoE-/~ atherosclerotic mice. Bio-distribution suggested 260% and 392% higher levels in aortas and carotid arteries, respectively, in comparison with wild-type mice [74]. In another study by Nahrendorf et al., fluorine-18 (F18)-labeled macrophage-targeted nanoparticles were utilized for PET-CT detection of inflammation in aortic aneurysm (AA)-induced ApoE-/~ mice. Aneurismal aortic sections revealed significantly higher uptake relative to wild-type aorta. Atherosclerotic plaques with macrophage infiltration exhibited lower PET signal than AA. The investigators also performed ex vivo imaging to validate in vivo PET data. Moreover, the researchers reported higher uptake of F18-labeled macrophage-targeted CLIO nanoparticles. For ex vivo imaging by autoradiography and fluorescence reflective microscopic studies, nanoparticles were labeled with near-infrared fluorochrome [75].
