Bimodal Imaging of Inflammation with SPECT/CT and MRI Using Iodine-125 Labeled VCAM-1 Targeting Microparticle Conjugates

Abstract

Upregulation of cell adhesion molecules on endothelial cells is a hallmark of inflammation and an early feature of several neurological conditions. Here, we describe bimodal in vivo imaging of this inflammatory event in the brain using functionalized micron-sized particles of iron oxide. The particles were conjugated to anti-VCAM-1 antibodies and subsequently labeled with iodine-125. Radiolabeling of the antibody-coated particles was straightforward and proceeded in high radiochemical yields using commercially available iodination tubes. The corresponding contrast agent was evaluated in a rat model of cerebral inflammation based on intracerebral injection of tumor necrosis factor alpha and a rat model of status epilepticus. Biodistribution studies and phosphorimaging of cryosections were used to verify in vivo imaging data obtained with single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). The contrast agent showed rapid and highly localized binding to the vasculature of inflamed brain tissue, and was effectively cleared from the blood pool within 2 min postinjection. Overall, the pattern of hypointensities observed with MRI was in good agreement with the distribution of the contrast agent as determined with SPECT and phosphorimaging; however, conspicuous differences in the signal intensities were observed. The results demonstrate that radiolabeled micron-sized particles of iron oxide enable multimodal in vivo imaging with MRI and nuclear techniques, and highlight the value of validating different imaging methods against one another.