Detection of Active Caspase-3 in Mouse Models of Stroke and Alzheimer's Disease with a Novel Dual Positron Emission Tomography/Fluorescent Tracer [Ga]Ga-TC3-OGDOTA

Overview

Journal Contrast Media Mol Imaging

Specialty Radiology

Date 2019 Feb 14

PMID 30755766

Citations 8

Authors

Valeriy G Ostapchenko

Jonatan Snir

Mojmir Suchy

Jue Fan

M Rebecca Cobb

Blaine A Chronik

Michael Kovacs

Vania F Prado

Robert H E Hudson

Stephen H Pasternak

Marco A M Prado

Robert Bartha

Affiliations

Soon will be listed here.

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 [Ga]Ga-TC3-OGDOTA containing a cell-penetrating peptide separated from fluorescent Oregon Green and Ga-bound labels by the caspase-3 recognition peptide DEVD. We hypothesized that this design would allow [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 -amyloid oligomers. In vivo, PET showed accumulation of [Ga]Ga-TC3-OGDOTA in the brain of mouse models of stroke or AD. Optical clearing revealed colocalization of [Ga]Ga-TC3-OGDOTA and cleaved caspase-3 in brain cells. In stroke, [Ga]Ga-TC3-OGDOTA accumulated in neurons in the penumbra area, whereas in AD mice [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.

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