pH Dependence of T₁ for ¹³ C-Labelled Small Molecules Commonly Used for Hyperpolarized Magnetic Resonance Imaging

Hyperpolarization is a method to enhance the nuclear magnetic resonance signal by up to five orders of magnitude. However, the hyperpolarized (HP) state is transient and decays with the spin-lattice relaxation time (T₁ ), which is on the order of a few tens of seconds. Here, we analyzed the pH-dependence of T₁ for commonly used HP ¹³ C-labelled small molecules such as acetate, alanine, fumarate, lactate, pyruvate, urea and zymonic acid. For instance, the T₁ of HP pyruvate is about 2.5 fold smaller at acidic pH (25 s, pH 1.7, B₀ =1 T) compared to pH close to physiological conditions (66 s, pH 7.3, B₀ =1 T). Our data shows that increasing hydronium ion concentrations shorten the T₁ of protonated carboxylic acids of most of the analyzed molecules except lactate. Furthermore it suggests that intermolecular hydrogen bonding at low pH can contribute to this T₁ shortening. In addition, enhanced proton exchange and chemical reactions at the pK_a appear to be detrimental for the HP-state.