Khattri Ram B, Sirusi Ali A, Suh Eul Hyun, Kovacs Zoltan, Merritt Matthew E
Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, USA.
Phys Chem Chem Phys. 2019 Aug 28;21(34):18629-18635. doi: 10.1039/c9cp03717a.
Polarization transfer from unpaired electron radicals to nuclear spins at low-temperature is achieved using microwave irradiation by a process broadly termed dynamic nuclear polarization (DNP). The resulting signal enhancement can easily exceed factors of 104 when paired with cryogenic cooling of the sample. Dissolution-DNP couples low temperature polarization methods with a rapid dissolution step, resulting in a highly polarized solution that can be used for metabolically sensitive magnetic resonance imaging (MRI). Hyperpolarized [1-13C]pyruvate is a powerful metabolic imaging agent for investigation of in vitro and in vivo cellular metabolism by means of NMR spectroscopy and MRI. Radicals (trityl OX063 and BDPA) with narrower EPR linewidths typically produce higher nuclear polarizations when carbon-13 is the target nucleus. Increased solid-state polarization is observed when narrow line radicals are doped with lanthanide ions such as Gd3+, Ho3+, Dy3+, and Tb3+. Earlier results have demonstrated an incongruence between DNP experiments with trityl and BDPA, where the optimal concentrations for polarization transfer are disparate despite similar electron spin resonance linewidths. Here, the effects of Ho-DOTA on the solid-state polarization of [1-13C]pyruvic acid were compared for 3.35 T (1.4 K) and 5 T (1.2 K) systems using BDPA as a radical. Multiple concentrations of BDPA were doped with variable concentrations of Ho-DOTA (0, 0.2, 0.5, 1, and 2 mM), and dissolved in 1 : 1 (v/v) of [1-13C] pyruvic acid/sulfolane mixture. Our results reveal that addition of small amounts of Ho-DOTA in the sample preparation increases the solid-state polarization for [1-13C] pyruvic acid, with the optimum Ho-DOTA concentration of 0.2 mM. Without Ho-DOTA doping, the optimum BDPA concentration found for 3.35 T (1.4 K) is 40 mM, and for 5 T (1.2 K) system it is about 60 mM. In both systems, inclusion of Ho-DOTA in the 13C DNP sample leads to a change in the breadth (ΔDNP) of the extrema between the P(+) and P(-) frequencies in microwave spectra. At no combination of BDPA and Ho3+ did polarizations reach those achievable with trityl. Simplified analysis of increased polarization as a function of decreased electron T1e used to explain results in trityl are insufficient to describe DNP with BDPA.
通过一个被广泛称为动态核极化（DNP）的过程，利用微波辐射可在低温下实现未配对电子自由基到核自旋的极化转移。当与样品的低温冷却相结合时，由此产生的信号增强很容易超过104倍。溶解-DNP将低温极化方法与快速溶解步骤相结合，产生一种高度极化的溶液，可用于代谢敏感磁共振成像（MRI）。超极化的[1-13C]丙酮酸是一种强大的代谢成像剂，可通过核磁共振波谱和MRI研究体外和体内细胞代谢。当以碳-13为目标核时，具有较窄电子顺磁共振（EPR）线宽的自由基（三苯甲基OX063和BDPA）通常会产生更高的核极化。当窄线自由基掺杂镧系离子如Gd3+、Ho3+、Dy3+和Tb3+时，会观察到固态极化增加。早期结果表明，使用三苯甲基和BDPA进行的DNP实验之间存在不一致，尽管电子自旋共振线宽相似，但极化转移的最佳浓度却不同。在此，以BDPA为自由基，比较了Ho-DOTA对[1-13C]丙酮酸在3.35 T（1.4 K）和5 T（1.2 K）系统中的固态极化的影响。向多种浓度的BDPA中掺杂不同浓度的Ho-DOTA（0、0.2、0.5、1和2 mM），并溶解在1:1（v/v）的[1-13C]丙酮酸/环丁砜混合物中。我们的结果表明，在样品制备中添加少量的Ho-DOTA可增加[1-13C]丙酮酸的固态极化，最佳Ho-DOTA浓度为0.2 mM。在不掺杂Ho-DOTA的情况下，3.35 T（1.4 K）时发现的最佳BDPA浓度为40 mM，5 T（1.2 K）系统时约为60 mM。在这两个系统中，13C DNP样品中加入Ho-DOTA会导致微波光谱中P(+)和P(-)频率之间极值的宽度（ΔDNP）发生变化。在BDPA和Ho3+的任何组合下，极化都未达到使用三苯甲基时所能达到的水平。用于解释三苯甲基中结果的将极化增加作为电子T1e降低的函数的简化分析不足以描述使用BDPA的DNP。
