Author/Authors :
Ostapchenko, Valeriy G University of Western Ontario - Richmond Street - London, Canada , Snir, Jonatan University of Western Ontario - Richmond Street - London, Canada , Suchy, Mojmir University of Western Ontario - Richmond Street - London, Canada , Fan, Jue University of Western Ontario - Richmond Street - London, Canada , Rebecca Cobb, M University of Western Ontario - Richmond Street - London, Canada , Chronik, Blaine A Department of Medical Biophysics - University of Western Ontario - Richmond Street - London, Canada , Kovacs, Michael Department of Medical Biophysics - University of Western Ontario - Richmond Street - London, Canada , Prado, Vania F. University of Western Ontario - Richmond Street - London, Canada , Hudson, Robert H. E Department of Chemistry - University of Western Ontario - Richmond Street - London, Canada , Pasternak, Stephen H University of Western Ontario - Richmond Street - London, Canada , Prado, Marco A. M University of Western Ontario - Richmond Street - London, Canada , Bartha, Robert University of Western Ontario - Richmond Street - London, Canada
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
uorescent 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]GaTC3-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.
