Real-time tracking of dissociation of hyperpolarized $^{\mathrm{89}}$Y-DTPA: a model for degradation of open-chain Gd$^{\mathrm{3+}}$ MRI contrast agents

Gadolinium (Gd) complexes are widely used relaxation-based clinical contrast agents in magnetic resonance imaging (MRI). Gd-based MRI contrast agents with open-chain ligand such as Gd-DTPA, commercially known as magnevist, are less stable compared to Gd complexes with macrocyclic ligands such as GdDOTA (Dotarem). The dissociation of Gd-DPTA into Gd ion and DTPA ligand under certain biological conditions such as high zinc levels can potentially cause kidney damage. Since Gd is paramagnetic, direct NMR detection of the Gd-DTPA dissociation is quite challenging due to ultra-short relaxation times. In this work, we have investigated Y-DTPA as a model for Gd-DPTA dissociation under high zinc content solutions. Using dissolution dynamic nuclear polarization (DNP), the $^{\mathrm{89}}$Y NMR signal is amplified by several thousand-fold. Due to the the relatively long T$_{\mathrm{1}}$ relaxation time of $^{\mathrm{89}}$Y which translates to hyperpolarization lifetime of several minutes, the dissociation of Y-DTPA can be tracked in real-time by hyperpolarized $^{\mathrm{89}}$Y NMR spectroscopy. Dissociation kinetic rates and implications on the degradation of open-chain Gd$^{\mathrm{3+}}$ MRI contrast agents will be discussed.