Table of Contents Author Guidelines Submit a Manuscript
Contrast Media & Molecular Imaging
Volume 2019, Article ID 6403274, 17 pages
https://doi.org/10.1155/2019/6403274
Research Article

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

1Robarts Research Institute, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5B7
2Department of Medical Biophysics, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5B7
3Department of Chemistry, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5B7
4Neuroscience Program, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5B7
5Department of Physics and Astronomy, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5B7
6Lawson Health Research Institute, 268 Grosvenor Street, London, ON, Canada N6A 4V2
7Department of Physiology and Pharmacology, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5B7
8Department of Anatomy and Cell Biology, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5B7
9Department of Clinical Neurological Sciences, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5B7

Correspondence should be addressed to Marco A. M. Prado; ac.strabor@odarpm and Robert Bartha; ac.strabor@ahtrabr

Received 17 July 2018; Revised 20 October 2018; Accepted 19 November 2018; Published 14 January 2019

Academic Editor: Giancarlo Pascali

Copyright © 2019 Valeriy G. Ostapchenko et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 [68Ga]Ga-TC3-OGDOTA containing a cell-penetrating peptide separated from fluorescent Oregon Green and 68Ga-bound labels by the caspase-3 recognition peptide DEVD. We hypothesized that this design would allow [68Ga]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 [68Ga]Ga-TC3-OGDOTA in the brain of mouse models of stroke or AD. Optical clearing revealed colocalization of [68Ga]Ga-TC3-OGDOTA and cleaved caspase-3 in brain cells. In stroke, [68Ga]Ga-TC3-OGDOTA accumulated in neurons in the penumbra area, whereas in AD mice [68Ga]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.