Hyperpolarized 15N-labeled, deuterated tris (2-pyridylmethyl)amine as an MRI sensor of freely available Zn2

Eul Hyun Suh; Jae Mo Park; Lloyd Lumata; A Dean Sherry; Zoltan Kovacs

doi:10.1038/s42004-020-00426-6

Hyperpolarized ¹⁵N-labeled, deuterated tris (2-pyridylmethyl)amine as an MRI sensor of freely available Zn²

Commun Chem. 2020:3:185. doi: 10.1038/s42004-020-00426-6. Epub 2020 Dec 9.

Authors

Eul Hyun Suh¹, Jae Mo Park^{1

2

3}, Lloyd Lumata⁴, A Dean Sherry^{1

2

5}, Zoltan Kovacs^{1

5}

Affiliations

¹ Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
² Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
³ Department of Electrical and Computer Engineering, University of Texas at Dallas, Richardson, TX 75080, USA.
⁴ Department of Physics, University of Texas Dallas, Richardson, TX 75080, USA.
⁵ Department of Chemistry and Biochemistry, University of Texas Dallas, Richardson, TX 75080, USA.

Abstract

Dynamic nuclear polarization (DNP) coupled with ¹⁵N magnetic resonance imaging (MRI) provides an opportunity to image quantitative levels of biologically important metal ions such as Zn²⁺, Mg²⁺ or Ca²⁺ using appropriately designed ¹⁵N enriched probes. For example, a Zn-specific probe could prove particularly valuable for imaging the tissue distribution of freely available Zn²⁺ ions, an important known metal ion biomarker in the pancreas, in prostate cancer, and in several neurodegenerative diseases. In the present study, we prepare the cell-permeable, ¹⁵N-enriched, d₆-deuterated version of the well-known Zn²⁺ chelator, tris(2-pyridylmethyl)amine (TPA) and demonstrate that the polarized ligand had favorable T₁ and linewidth characteristics for ¹⁵N MRI. Examples of how polarized TPA can be used to quantify freely available Zn²⁺ in homogenized human prostate tissue and intact cells are presented.

Grants and funding

P41 EB015908/EB/NIBIB NIH HHS/United States