Detection of Active Caspase-3 in Mouse Models of Stroke and Alzheimer's Disease with a Novel Dual Positron Emission Tomography/Fluorescent Tracer [68Ga]Ga-TC3-OGDOTA. (14th January 2019)

• Record Type: Journal Article
• Authors: Ostapchenko, Valeriy G.; Snir, Jonatan; Suchy, Mojmir; Fan, Jue; Cobb, M. Rebecca; Chronik, Blaine A.; Kovacs, Michael; Prado, Vania F.; Hudson, Robert H. E.; Pasternak, Stephen H.; Prado, Marco A. M.; Bartha, Robert
• Other Names: Pascali Giancarlo Academic Editor.
• Is Part Of: Contrast media & molecular imaging. Volume 2019(2019)
• Publication Date: 2019-01-14
• Subjects: Diagnostic imaging -- Periodicals; Magnetic resonance imaging -- Periodicals; Contrast media (Diagnostic imaging) -- Periodicals; Contrast Media -- Periodicals; Diagnostic Imaging -- Periodicals; Substances de contraste -- Périodiques; Diagnostics moléculaires -- Périodiques; Imagerie médicale; Substance de contraste; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.0754
• DOI: 10.1155/2019/6403274
• Languages: English
• ISSNs: 1555-4309

Abstract

Abstract : Apoptosis is a feature of stroke and Alzheimer's disease (AD), yet there is no accepted method to detect or follow apoptosis in the brain in vivo. We developed a bifunctional tracer [ 68 Ga]Ga-TC3-OGDOTA containing a cell-penetrating peptide separated from fluorescent Oregon Green and 68 Ga-bound labels by the caspase-3 recognition peptide DEVD. We hypothesized that this design would allow [ 68 Ga]Ga-TC3-OGDOTA to accumulate in apoptotic cells. In vitro, Ga-TC3-OGDOTA labeled apoptotic neurons following exposure to camptothecin, oxygen-glucose deprivation, and β -amyloid oligomers. In vivo, PET showed accumulation of [ 68 Ga]Ga-TC3-OGDOTA in the brain of mouse models of stroke or AD. Optical clearing revealed colocalization of [ 68 Ga]Ga-TC3-OGDOTA and cleaved caspase-3 in brain cells. In stroke, [ 68 Ga]Ga-TC3-OGDOTA accumulated in neurons in the penumbra area, whereas in AD mice [ 68 Ga]Ga-TC3-OGDOTA was found in single cells in the forebrain and diffusely around amyloid plaques. In summary, this bifunctional tracer is selectively associated with apoptotic cells in vitro and in vivo in brain disease models and represents a novel tool for apoptosis detection that can be used in neurodegenerative diseases.