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

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.