Targeted gold-coated iron oxide nanoparticles for CD163 detection in atherosclerosis by MRI

CD163 is a membrane receptor expressed by macrophage lineage. Studies performed in atherosclerosis have shown that CD163 expression is increased at inflammatory sites, pointing at the presence of intraplaque hemorrhagic sites or asymptomatic plaques. Hence, imaging of CD163 expressing macrophages is an interesting strategy in order to detect atherosclerotic plaques. We have prepared a targeted probe based on gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody for the specific detection of CD163 by MRI. Firstly, the specificity of the targeted probe was validated in vitro by incubation of the probe with CD163(+) or (−) macrophages. The probe was able to selectively detect CD163(+) macrophages both in human and murine cells. Subsequently, the targeted probe was injected in 16 weeks old apoE deficient mice developing atherosclerotic lesions and the pararenal abdominal aorta was imaged by MRI. The accumulation of probe in the site of interest increased over time and the signal intensity decreased significantly 48 hours after the injection. Hence, we have developed a highly sensitive targeted probe capable of detecting CD163-expressing macrophages that could provide useful information about the state of the atheromatous lesionsThis work was funded by Spanish Government through a Plan Nacional (CTQ2011–27268), FEDER funds through the Fondo de Investigación Sanitaria (PI10/00072, PI13/00051, PI13/00395, PI13/00802, PI14/00883 and PI14/00386), CIBERDEM group, RETICS RD12/0042/0038, Programa Miguel Servet (CP10/00479) and cvREMOD CENIT project (CEN-20091044), the Basque Government through Etortek 2011 (IE11–301), and Fundacion Lilly, Spanish Society of Atherosclerosis, Spanish Society of Nephrology and Fundacion Renal Iñigo Alvarez de Toled

A cortical vascular model for examining the specificity of the laminar BOLD signal

Blood oxygenation level dependent (BOLD) functional MRI has been used for inferring layer specific activation in humans. However, intracortical veins perpendicular to the cortical surface are suspected to degrade the laminar specificity as they drain blood from the microvasculature and BOLD signal is carried over from lower to upper cortical layers on its way to the pial surface. In this work, a vascular model of the cortex is developed to investigate the laminar specificity of the BOLD signal for Spin Echo (SE) and Gradient Echo (GE) following the integrative model presented by Uludağ et al. (2009). The results of the simulation show that the laminar point spread function (PSF) of the BOLD signal presents similar features across all layers. The PSF for SE is highly localised whereas for GE there is a flat tail running to the pial surface, with amplitude less than a quarter of the response from the layer itself. Consequently the GE response at any layer will also contain a contribution accumulated from all lower layers

Imaging the role of TLR4 on cell proliferation and inflammation after cerebral ischemia by PET

The influence of Toll-Like Receptor 4 (TLR4) on neurogenesis and inflammation has been scarcely explored so far by using neuroimaging techniques. For this purpose, we performed magnetic resonance imaging (MRI) and positron emission tomography (PET) with [18F]FLT and [11C]PK11195 at 2, 7 and 14 days following cerebral ischemia in TLR4+/+ and TLR4-/- mice. MRI showed similar infarction volumes in both groups. Despite this, PET with [18F]FLT and [11C]PK11195 evidenced an increase of neurogenesis and a decrease of inflammation in TLR4-/- mice after ischemia. These results evidence the versatility of neuroimaging techniques to monitor the role of TLR4 after cerebral ischemia

Imaging the role of toll-like receptor 4 on cell proliferation and inflammation after cerebral ischemia by positron emission tomography

The influence of toll-like receptor 4 on neurogenesis and inflammation has been scarcely explored so far by using neuroimaging techniques. For this purpose, we performed magnetic resonance imaging and positron emission tomography with 3'-deoxy-3'-[(18)F]fluorothymidine and [(11)C]PK11195 at 2, 7, and 14 days following cerebral ischemia in TLR4(+/+)and TLR4(-/-)mice. MRI showed similar infarction volumes in both groups. Despite this, positron emission tomography with 3'-deoxy-3'-[(18)F]fluorothymidine and [(11)C]PK11195 evidenced an increase of neurogenesis and a decrease of inflammation in TLR4(-/-)mice after ischemia. These results evidence the versatility of neuroimaging techniques to monitor the role of toll-like receptor 4 after cerebral ischemia.Depto. de Farmacología y ToxicologíaFac. de MedicinaTRUEpu