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Nanotherapy has recently emerged as an experimental treatment option for atherosclerosis. To fulfill its promise, robust noninvasive imaging approaches for subject selection and treatment evaluation are warranted. To that end, we here present a positron emission tomography (PET)-based method for quantification of liposomal nanoparticle uptake in the atherosclerotic vessel wall. We evaluated a modular procedure to label liposomal nanoparticles with the radioisotope zirconium-89 (89Zr). Their biodistribution and vessel wall targeting in a rabbit atherosclerosis model was evaluated up to 15 days after intravenous injection by PET/computed tomography (CT) and PET/magnetic resonance imaging (PET/MRI). Vascular permeability was assessed in vivo using 3-dimensional dynamic contrast-enhanced MRI (3D DCE-MRI) and ex vivo using near-infrared fluorescence (NIRF) imaging. The 89Zr-radiolabeled liposomes displayed a biodistribution pattern typical of long-circulating nanoparticles. Importantly, they markedly accumulated in atherosclerotic lesions in the abdominal aorta, as evident on PET/MRI and confirmed by autoradiography, and this uptake moderately correlated with vascular permeability. The method presented herein facilitates the development of nanotherapy for atherosclerotic disease as it provides a tool to screen for nanoparticle targeting in individual subjects' plaques.
This article was published in the following journal.
Name: Bioconjugate chemistry
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An imaging technique using compounds labelled with short-lived positron-emitting radionuclides (such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18) to measure cell metabolism. It has been useful in study of soft tissues such as CANCER; CARDIOVASCULAR SYSTEM; and brain. SINGLE-PHOTON EMISSION-COMPUTED TOMOGRAPHY is closely related to positron emission tomography, but uses isotopes with longer half-lives and resolution is lower.
An imaging technique that combines a POSITRON-EMISSION TOMOGRAPHY (PET) scanner and a CT X RAY scanner. This establishes a precise anatomic localization in the same session.
The creation of a visual display of the inside of the entire body of a human or animal for the purposes of diagnostic evaluation. This is most commonly achieved by using MAGNETIC RESONANCE IMAGING; or POSITRON EMISSION TOMOGRAPHY.
A method of computed tomography that uses radionuclides which emit a single photon of a given energy. The camera is rotated 180 or 360 degrees around the patient to capture images at multiple positions along the arc. The computer is then used to reconstruct the transaxial, sagittal, and coronal images from the 3-dimensional distribution of radionuclides in the organ. The advantages of SPECT are that it can be used to observe biochemical and physiological processes as well as size and volume of the organ. The disadvantage is that, unlike positron-emission tomography where the positron-electron annihilation results in the emission of 2 photons at 180 degrees from each other, SPECT requires physical collimation to line up the photons, which results in the loss of many available photons and hence degrades the image.
An imaging technique using a device which combines TOMOGRAPHY, EMISSION-COMPUTED, SINGLE-PHOTON and TOMOGRAPHY, X-RAY COMPUTED in the same session.
Radiology is the branch of medicine that studies imaging of the body; X-ray (basic, angiography, barium swallows), ultrasound, MRI, CT and PET. These imaging techniques can be used to diagnose, but also to treat a range of conditions, by allowing visuali...