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Imaging of Hypoxia, Apoptosis, and Inflammation
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
Stavros Spiliopoulos, Athanasios Diamantopoulos
Another characteristic of apoptotic cells is the phenomenon of membrane permeability alteration, which provides a valid target for membrane-based probes of in vivo apoptosis imaging. Two novel radiopharmaceutical agents, N, N9-didansylcystine and 5-dimethylamino-1-naphthalenesulfonyl-α-ethyl-fluoroalanine (NST-732) with the trade name Apo-Sense, have been recently developed. It has been proposed that these 18F containing compounds are excluded from normal cells but accumulate in apoptotic cells when membrane phospholipids are altered early in apoptosis enabling in vivo PET imaging (Aloya et al. 2006). The ability of this molecule to rapidly concentrate within damaged cells potentially provides superior imaging compared to annexin V (Korngold et al. 2008).
The Emergence of “Magnetic and Fluorescent” Multimodal Nanoparticles as Contrast Agents in Bioimaging
Published in Wolfgang Sigmund, Hassan El-Shall, Dinesh O. Shah, Brij M. Moudgil, Particulate Systems in Nano- and Biotechnologies, 2008
P. Sharma, A. Singh, S.C. Brown, G.A. Walter, S. Santra, S.R. Grobmyer, E.W. Scott, B.M. Moudgil
The overall size of the construct after lipid modification was about 10 nm, which is significantly less than other nanoparticulate contrast agents.40,212 The multimodal character and the biological specificity were demonstrated by specific labeling of human umbilical vein endothelial cells in vitro. A similar multimodal nanoparticle construct was bioconjugated with annexin A5 and used for cellular labeling. Annexin A5 binds with high affinity to phosphatidylserine, which is asymmetrically distributed PS at the outer monolayer of the cell membrane of apoptotic cells.213 The specific targeting ability of these particles was demonstrated in vitro using a T lymphoma cell line. Strong signal enhancement from apoptotic labeled cells using MR and fluorescence was detected.
Merging optical with other imaging approaches
Published in Yi-Hwa Liu, Albert J. Sinusas, Hybrid Imaging in Cardiovascular Medicine, 2017
Doug Yeager, Nicholas Dana, Stanislav Emelianov
Investigational dual-labeled contrast agents combining fluorescence and nuclear imaging have been developed for a wide range of cellular and molecular targets. For example, a dextran-coated magnetofluorescent nanoparticle labeled with the radionuclide 64Cu was utilized for the imaging of macrophages in inflammatory atherosclerosis in mice using PET, MRI, and FMT (Nahrendorf et al. 2008). The study found that elevated signals from the accumulation of contrast agents observed within the aortic root and arch exhibited a target-to-background ratio of 5.1, and accumulated doses within the aortas and carotid arteries were found to be 260% and 392% greater in the atherosclerotic mice than in wild-type controls. A similar platform, comprising the radionuclide 18F-CLIO and a near-infrared fluorochrome, was utilized for the detection of macrophages within atherosclerotic mice aortic aneurysms (Nahrendorf et al. 2011). Signals obtained from the aneurysms were found to be higher than both wild type aorta and atherosclerotic plaques. Dual-modality micelles labeled with the radionuclide 111In and near-infrared fluorescent Cy7-like dye and conjugated with Annexin V, which specifically binds to phosphatidylserine residues that are exposed on the cell surface during apoptosis, have also been demonstrated for the hybrid imaging of apoptosis (Zhang et al. 2011a). Annexin V-labeled, multimodality contrast agents represent a natural extension of a nuclear imaging targeting strategy, which has been widely utilized to investigate apoptosis in cardiac tissue (Narula et al. 2001; Kietselaer et al. 2004, 2007).
Neurotoxicity of β-HgS differs from environmental mercury pollutants (MeHgCl and HgCl2) in Neuro-2a cell
Published in International Journal of Environmental Health Research, 2021
Zhenghua Xia, Hongtao Bi, Cen Li, Lujing Geng, Muhammad Usman, Yuzhi Du, Lixin Wei
Phosphatidylserine (PS) would onto the outer leaflet of the cellular membrane in the early stages of apoptosis. Annexin V in the apoptosis detection kit is conjugated to FITC, so Annexin V could selective binding with PS and then we can identify apoptotic cells by flow cytometer (FCM). Early apoptotic, late apoptotic cells and necrotic cells will bind Annexin V-FITC. PI is excluded by viable cells (FITC-negative) and early apoptotic cells (FITC-positive), so late apoptotic and necrotic cells stain with both Annexin V-FITC and PI. We tested apoptosis rates and necrotic cells of Neuro-2a cell by FCM after staining with Annexin V-FITC and PI. The visualization of apoptotic cells by FCM was showed in Figure 4(a). Quadrants FITC+/PI- in Figure 3 show early stage apoptosis cell and Quadrants FITC+/PI+ show late apoptotic cells or necrotic cells, stained with FITC and PI. Quadrants FITC-/PI- of the histograms show living, intact cells without apoptosis. The cells in Quadrant FITC-/PI+ represent the detection errors within the allowable range. According to analysis the apoptotic rate, we found that with the extension of incubation time (6 h to 24 h), compared with the control group, the apoptosis rates of β-HgS, MeHgCl and HgCl2 were increased in different degrees. The apoptotic rate of β-HgS was increased from 15.7% to 17.0%, MeHgCl was enhanced from 40.4% to 49.2%, HgCl2 was increased from 13.8% to 24.3% (Figure 4(b)).
Application of molecular imaging technology in neurotoxicology research
Published in Journal of Environmental Science and Health, Part C, 2018
Xuan Zhang, Qi Yin, Marc Berridge, Che Wang
One of the earliest markers of neurons that are undergoing apoptosis is the externalization of phosphatidylserine (PS), one of the four major phospholipids that makes up the cell membrane, from the intracellular to the extracellular side of the plasma membrane.[19–23] Surrounding normal cells and macrophages can identify the redistribution of PS as a signal for phagocytizing and digesting the components of the apoptotic cells.[24–26] As annexin-V binds to PS with high affinity and specificity, annexin V that is labeled with different radionuclides is a promising tracer for in vivo detection of cells that are undergoing programed cell death.[21,23,25,27,28]