Robert Ta1,2, Alex X Li1, Mojmir
Suchy3, Robert H. E. Hudson3, Stephen Pasternak4,5,
Robert Bartha1,2
1Imaging Research
Laboratories, Robarts Research Institute, London, Ontario, Canada; 2Medical
Biophysics, the University of Western Ontario, London, Ontario, Canada; 3Chemistry,
the University of Western Ontario, London, Ontario, Canada; 4Molecular
Brain Research Group, Robarts Research Institute, London, Ontario, Canada; 5Clinical
Neurological Sciences, the University of Western Ontario, London, Ontario,
Canada
A novel contrast agent, Gd3+-DOTA-CAT, has been developed for in-vivo magnetic resonance imaging of Cathepsin-D activity in Alzheimers disease. A cell-penetrating-peptide was attached to increase the agents ability to cross the blood-brain-barrier. A Cathepsin-D recognition site was used for enzymatic detection of Gd3+-DOTA-CAT upon brain tissue penetration. We compared the MR sensitivity of Gd3+-DOTA-CAT to Gd3+-DTPA(Magnevist) to evaluate the potential in-vivo imaging of this compound. Injection of 10 mM Gd3+-DOTA-CAT in a transgenic Alzheimers disease mouse produced increased signal intensity within the brain, cerebral and non-cerebral vasculature. Gd3+-DOTA-CAT demonstrates significant potential as a MRI contrast agent for Cathepsin-D activity in-vivo.
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