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

Dynamic nuclear polarization (DNP) coupled with (15)N magnetic resonance imaging (MRI) provides an opportunity to image quantitative levels of biologically important metal ions such as Zn(2+), Mg(2+) or Ca(2+) using appropriately designed (15)N enriched probes. For example, a Zn-specific probe could prove particularly valuable for imaging the tissue distribution of freely available Zn(2+) 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, (15)N-enriched, d(6)-deuterated version of the well-known Zn(2+) chelator, tris(2-pyridylmethyl)amine (TPA) and demonstrate that the polarized ligand had favorable T(1) and linewidth characteristics for (15)N MRI. Examples of how polarized TPA can be used to quantify freely available Zn(2+) in homogenized human prostate tissue and intact cells are presented.