TY - JOUR
T1 - Hyperpolarized 15N-labeled, deuterated tris(2-pyridylmethyl)amine as an MRI sensor of freely available Zn2+
AU - Suh, Eul Hyun
AU - Park, Jae Mo
AU - Lumata, Lloyd
AU - Sherry, A. Dean
AU - Kovacs, Zoltan
N1 - Funding Information:
We thank Dr. Douglas Strand and Dr. Jer-Tsong Hsieh at the Department of Urology, the University of Texas Southwestern Medical Center, Dallas, TX for providing the human prostate tissue samples and PNT1A-WT cell. We acknowledge partial financial support for this work from the National Institutes of Health (R37-HR034557 and P41-EB015908), the Texas Institute for Brain Injury and Repair, the Robert A. Welch Foundation (AT-584, AT-1877-03242018 and I-2009-20190330), and Collaborative Biomedical Research Award (CoBRA).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85097446188&partnerID=8YFLogxK
U2 - 10.1038/s42004-020-00426-6
DO - 10.1038/s42004-020-00426-6
M3 - Article
AN - SCOPUS:85097446188
SN - 2399-3669
VL - 3
JO - Communications Chemistry
JF - Communications Chemistry
IS - 1
M1 - 185
ER -