In vivo molecular imaging of apoptosis and necrosis in atherosclerotic plaques using microSPECT-CT and microPET-CT imaging. 2014

M De Saint-Hubert, and M Bauwens, and N Deckers, and M Drummen, and K Douma, and P Granton, and G Hendrikx, and D Kusters, and J Bucerius, and C P M Reutelingsperger, and F M Mottaghy
Department of Nuclear Medicine, MUMC, Maastricht, The Netherlands, marijke.de.sainthubert@mumc.nl.

OBJECTIVE The purpose of this paper is to study molecular imaging of apoptosis and necrosis, two key players in atherosclerosis instability, using a multimodal imaging approach combining single photon emission computed tomography (SPECT), positron emission tomography (PET), and computed tomography (CT). METHODS Collar-induced carotid atherosclerosis ApoE knockout mice were imaged with (99m)Tc-AnxAF568 SPECT-CT to study apoptosis and sequentially with PET-CT following (124)I-Hypericin ((124)I-Hyp) injection to visualize necrosis. RESULTS SPECT depicted increased (99m)Tc-AnxAF568 uptake in both atherosclerotic carotid arteries, whereas our data suggest that this uptake is not merely apoptosis related. Although PET of (124)I-Hyp was hampered by the slow blood clearance in atherosclerotic mice, (124)I-Hyp was able to target necrosis in the atherosclerotic plaque. CONCLUSIONS Both (99m)Tc-AnxAF568 and (124)I-Hyp uptake are increased in atherosclerotic carotid vasculature compared to control arteries. While apoptosis imaging remains challenging, necrosis imaging can be feasible after improving the biodistribution characteristics of the probe.

UI MeSH Term Description Entries
D009336 Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply.
D010569 Perylene A 20-carbon dibenz(de,kl)anthracene that can be viewed as a naphthalene fused to a phenalene or as dinaphthalene. It is used as fluorescent lipid probe in the cytochemistry of membranes and is a polycyclic hydrocarbon pollutant in soil and water. Derivatives may be carcinogenic. Perilene,Peri-Dinaphthalene,Peri Dinaphthalene
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000873 Anthracenes A group of compounds with three aromatic rings joined in linear arrangement.
D013667 Technetium The first artificially produced element and a radioactive fission product of URANIUM. Technetium has the atomic symbol Tc, and atomic number 43. All technetium isotopes are radioactive. Technetium 99m (m Technetium 99m,99m, Technetium
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions
D014057 Tomography, X-Ray Computed Tomography using x-ray transmission and a computer algorithm to reconstruct the image. CAT Scan, X-Ray,CT Scan, X-Ray,Cine-CT,Computerized Tomography, X-Ray,Electron Beam Computed Tomography,Tomodensitometry,Tomography, Transmission Computed,X-Ray Tomography, Computed,CAT Scan, X Ray,CT X Ray,Computed Tomography, X-Ray,Computed X Ray Tomography,Computerized Tomography, X Ray,Electron Beam Tomography,Tomography, X Ray Computed,Tomography, X-Ray Computer Assisted,Tomography, X-Ray Computerized,Tomography, X-Ray Computerized Axial,Tomography, Xray Computed,X Ray Computerized Tomography,X Ray Tomography, Computed,X-Ray Computer Assisted Tomography,X-Ray Computerized Axial Tomography,Beam Tomography, Electron,CAT Scans, X-Ray,CT Scan, X Ray,CT Scans, X-Ray,CT X Rays,Cine CT,Computed Tomography, Transmission,Computed Tomography, X Ray,Computed Tomography, Xray,Computed X-Ray Tomography,Scan, X-Ray CAT,Scan, X-Ray CT,Scans, X-Ray CAT,Scans, X-Ray CT,Tomographies, Computed X-Ray,Tomography, Computed X-Ray,Tomography, Electron Beam,Tomography, X Ray Computer Assisted,Tomography, X Ray Computerized,Tomography, X Ray Computerized Axial,Transmission Computed Tomography,X Ray Computer Assisted Tomography,X Ray Computerized Axial Tomography,X Ray, CT,X Rays, CT,X-Ray CAT Scan,X-Ray CAT Scans,X-Ray CT Scan,X-Ray CT Scans,X-Ray Computed Tomography,X-Ray Computerized Tomography,Xray Computed Tomography
D015899 Tomography, Emission-Computed, Single-Photon 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. CAT Scan, Single-Photon Emission,CT Scan, Single-Photon Emission,Radionuclide Tomography, Single-Photon Emission-Computed,SPECT,Single-Photon Emission-Computed Tomography,Tomography, Single-Photon, Emission-Computed,Single-Photon Emission CT Scan,Single-Photon Emission Computer-Assisted Tomography,Single-Photon Emission Computerized Tomography,CAT Scan, Single Photon Emission,CT Scan, Single Photon Emission,Emission-Computed Tomography, Single-Photon,Radionuclide Tomography, Single Photon Emission Computed,Single Photon Emission CT Scan,Single Photon Emission Computed Tomography,Single Photon Emission Computer Assisted Tomography,Single Photon Emission Computerized Tomography,Tomography, Single-Photon Emission-Computed
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis

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