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-Reference-Cited by-同舟云学术

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

Published:2019-01-14 Issue: Volume:2019 Page:1-17
ISSN:1555-4309
Container-title:Contrast Media & Molecular Imaging
language:en
Short-container-title:Contrast Media & Molecular Imaging

Author:

Ostapchenko Valeriy G.¹^ORCID,Snir Jonatan¹²,Suchy Mojmir¹³,Fan Jue¹,Cobb M. Rebecca¹⁴,Chronik Blaine A.²⁵,Kovacs Michael²⁶,Prado Vania F.¹⁷⁸,Hudson Robert H. E.³^ORCID,Pasternak Stephen H.¹⁹,Prado Marco A. M.¹⁷⁸^ORCID,Bartha Robert¹²^ORCID

Affiliation:

1. Robarts Research Institute, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5B7

2. Department of Medical Biophysics, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5B7

3. Department of Chemistry, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5B7

4. Neuroscience Program, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5B7

5. Department of Physics and Astronomy, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5B7

6. Lawson Health Research Institute, 268 Grosvenor Street, London, ON, Canada N6A 4V2

7. Department of Physiology and Pharmacology, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5B7

8. Department of Anatomy and Cell Biology, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5B7

9. Department of Clinical Neurological Sciences, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5B7

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.

Funder

Canadian Institutes of Health Research

Publisher

Hindawi Limited

Subject

Radiology Nuclear Medicine and imaging

Link

http://downloads.hindawi.com/journals/cmmi/2019/6403274.pdf

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