MediLumine’s Fenestra® imaging agents for preclinical computed tomography will be presented at the upcoming WMIC.
Fenestra® LC and Fenestra® VC imaging agents are used for a wide array of applications in preclinical computed tomography and molecular imaging. These hepatocyte selective nano-emulsions help to enable co-registration of soft tissue CT data for multimodal molecular imaging, quantification of metastatic tumor burdens, 4D imaging for characterization of murine cardiovascular disease and quantitative assessments of anti-angiogenic therapies.
Fenestra©LC nano-emulsions are manufactured by sheer induced rupturing with 10% iodinated triglycerides. The resulting particle size of lipid spheres are under 150 nm, the size required to pass through fenestrae in hepatic portal vessels and access hepatocytes for ApoE mediated uptake.Biologically, Fenestra©LC takes advantage of lipoprotein metabolism by mimicking chylomicron remnants and localizing contrast-producing lipids into hepatocytes allowing for prolonged liver micro-CT.
Proof of concept studies have shown that like endogenous chylomicron remnants Fenestra® LC lipid spheres are taken up via ApoE receptor. Experiments with Female ApoE knockout mice and normal B6 mice confirmed ApoE activation of Fenestra® LC nano-emulsion. Liver uptake was significantly delayed as indicated by decreased liver densities in the ApoE knockout mice relative to wild-?type controls. Axial view of normal B6 mice shows negative contrast for hepatic vessels and contrast enhancement for liver parenchyma opposite to contrast observed in these tissues with ApoE knockout mice.
Fully Eliminated by Hepatocytes
Comparison of microCT coronal images (thorax and abdomen) of three C57 mice injected at 7.5, 10, or 15 ml/kg levels of contrast and imaged at 2 h post-injection and then daily for up to 7 days. At doses of 7.5 to 10 ml/kg, Fenestra® LC is completely eliminated by hepatocyte metabolism. At doses of 15 ml/kg, Fenestra® LC is partially taken up through RES system allowing for prolonged liver imaging one week post-injection.
Prolonged Vascular Imaging
Coronal and sagittal scans of male mouse obtained on the MicroCAT II 3 hr after IV administration of Fenestra VC. Coronal image shows Fenestra VC continues to produce vascular contrast 3 hr after injection, clearly delineating the ventricles and ventricular wall, the aorta and the carotid arteries in the neck. Small vessels are clearly observed in the liver, which is only slightly enhanced due to the initial elimination of the contrast agent, although the gall bladder has yet to enhance as a result of excretion of the metabolized agent.
The sagittal view shows a major vessel diagonally traversing the liver with a number of smaller vessels seen in cross section. The heart and the aorta are readily visualized as is another vessel, which appears to bifurcate just below the base of the skull. Sagittal image shows the descending aorta and several other arteries in the abdomen. The heart, aorta and several additional vessels are seen in the thorax and neck of the mouse. In all three images the chow-induced artifacts are evident in the intestines.
Volumetric representations of vascular enhancement from scans of a male mouse obtained on the MicroCAT II 3 hr after IV administration of Fenestra VC. Fenestra VC produces prolonged vascular contrast enhancement throughout the entire body from a single peripheral injection.