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Abstract #2460

Insights from the Characterisation of the NAD+ Biosynthesis Pathway via in-vitro CEST MRI

Festus Slade1,2,3,4,5, Wilfred Lam2,6, Joanna F Collingwood7, and Greg Stanisz2,6,8
1School of Engineering, University of Warwick, Coventry, United Kingdom, 2Physical Sciences, Sunnybrook Research Institute,, Toronto, ON, Canada, 3Medical Biophysics, University of Toronto, Toronto, ON, Canada, 4University of Warwick, Department of Chemistry,, Coventry, United Kingdom, 5University of Warwick, School of Engineering, Coventry, United Kingdom, 6Medical Biophysics, University of Toronto,, Toronto, ON, Canada, 7University of Warwick, School of Engineering,, Coventry, United Kingdom, 8Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada

Synopsis

Keywords: CEST / APT / NOE, Alzheimer's Disease, NAD+

Motivation: Neurodegenerative diseases, particularly Alzheimer's, involve disrupted NAD+ and purine metabolic pathways. Understanding these disruptions can improve diagnostic sensitivity for clinical applications, especially using CEST MRI.

Goal(s): To characterise in-vitro CEST MRI properties of NAD+ and its biosynthesis precursors, focusing on sensitivity for neurodegenerative disease biomarkers linked to NAD+/purine metabolism.

Approach: In-vitro CEST MRI was used to analyse NAD+ and biosynthesis precursors, quantifying, characterising, and assigning distinct proton peaks to assess sensitivity as neurodegenerative disease biomarkers.

Results: High CEST contrast was achieved for NMN and NAD+, with NAD+ showing pH-dependent effects and up to 15% CEST contrast for its amine moiety (2.03ppm).

Impact: This study may impact neurodegenerative disease research by enabling precise CEST MRI-based tracking of NAD+ metabolism, specifically adenosine-linked pathways as elucidated (2.03ppm). This could deepen understanding of metabolic disruptions, opening new avenues for early diagnosis and targeted therapeutic monitoring.

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Keywords