Competitive Displacement Restores the Hyperpolarized ¹⁵N NMR Signal in Blood Plasma

Hyperpolarized (HP) NMR can improve the sensitivity of conventional NMR experiments by several orders of magnitude, thereby making it feasible to detect the signal of low sensitivity nuclei such as ¹³C and ¹⁵N nuclei in vivo. Hyperpolarized substrates are usually administered by direct injection into the bloodstream, and interaction with serum albumin can cause rapid decay of the hyperpolarized signal due to the shortening of the spin-lattice (T₁) relaxation time. Here we report that the ¹⁵N T₁ of ¹⁵N labeled, partially deuterated tris(2-pyridylmethyl)amine decreases dramatically upon binding to albumin to such an extent that no HP-¹⁵ signal could be detected. We also demonstrate that the signal could be restored using a competitive displacer, iophenoxic acid, which binds stronger to albumin than tris(2-pyridylmethyl)amine. The methodology presented here eliminates the undesirable effect of albumin binding and should widen the range of hyperpolarized probes for in vivo studies.