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.
Highlights
Cerebral inflammation occurs as a result of infection or injury and is known to be a feature of several neurological conditions such as stroke,[1] epilepsy,[2] traumatic brain injury,[3] brain tumors,[4,5] and Alzheimer’s disease.[6]
The low radioactivity levels in the bladder and thyroid, as seen by whole body single photon emission computed tomography (SPECT)/CT 20−25 min post-injection (Figure 1c), suggest that [125I]VCAM-MPIO remains largely intact after administration in vivo
The discrepancies between the measured tissue distribution of the contrast agent at 10 min p.i. and the whole body SPECT image (20−25 min p.i.), can at least in part be explained by the low density of lung tissue and the different units of quantification; whereas organ distribution is normalized to weight, SPECT provides a measure of radioactivity levels per volume
Summary
Cerebral inflammation occurs as a result of infection or injury and is known to be a feature of several neurological conditions such as stroke,[1] epilepsy,[2] traumatic brain injury,[3] brain tumors,[4,5] and Alzheimer’s disease.[6]. 1) expression using micron-sized particles of iron oxide (MPIOs) coupled with magnetic resonance imaging (MRI) has shown to be a highly sensitive and specific method of detecting and locating inflammation.[7−14] The low constitutive expression of VCAM-1 renders it an ideal target for molecular imaging. It is expressed on the surface of endothelial cells and can be used to monitor pathology or therapies in the brain without the need for contrast agents to cross the bloodbrain barrier (BBB). VCAM-1 mediates the rolling and extravasation of leukocytes across the vascular endothelium.[15]
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