Britton Chance Laboratory of Redox Imaging and Laboratory of Molecular Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Adv Exp Med Biol. 2022;1395:237-242. doi: 10.1007/978-3-031-14190-4_39.
Importance of the redox status of nicotinamide adenine dinucleotide (NAD), including its oxidized (NAD) and reduced (NADH) forms, has been shown in many biological processes. However, NAD(H) redox status assessment is traditionally limited to biochemical assays in vitro or optical redox imaging (ORI) for superficial tissues in vivo and for deep tissues ex vivo. In recent years, phosphorous-31 magnetic resonance spectroscopy (P-MRS) was utilized to quantify NAD, NADH, and the redox ratio NAD/NADH in normal tissues in vivo. The quantification is based on the spectral fitting of the upfield shoulder of the αATP peak that contains signals of NAD (a quartet) and NADH (a singlet), assuming pH-independence of peak positions. To evaluate the feasibility of measuring tumour NAD(H) redox status in vivo, we fitted single voxel P-MR spectra of subcutaneous mouse xenografts of human breast cancer cell lines acquired on a 9.4-T horizontal bore preclinical MR scanner. We found larger variations in the chemical shift offsets of NAD and NADH from αATP in these tumours than the literature values of normal tissues. Furthermore, our P-MR spectra of αATP, NAD and NADH solution phantoms indicated that the chemical shift of αATP and thus the offsets between NAD(H) and αATP were pH dependent. Therefore, whether tumour pH should be incorporated into the spectral fitting model should be further evaluated. Additionally, spectral resolution and signal-to-noise ratio should be improved by optimising P-MRS protocols, increasing data acquisition time, and using a more sensitive coil for signal detection.
烟酰胺腺嘌呤二核苷酸（NAD）的氧化还原状态（包括其氧化形式 NAD 和还原形式 NADH）在许多生物过程中都很重要。然而，NAD（H）氧化还原状态的评估传统上仅限于体外生化测定或体内浅层组织的光学氧化还原成像（ORI）以及离体深层组织。近年来，磷-31 磁共振波谱（P-MRS）被用于定量体内正常组织中的 NAD、NADH 和 NAD/NADH 氧化还原比。定量是基于αATP 峰的上磁场肩的光谱拟合，该峰包含 NAD（四重峰）和 NADH（单峰）的信号，假设峰位置与 pH 无关。为了评估在体测量肿瘤 NAD（H）氧化还原状态的可行性，我们对在 9.4-T 水平孔预临床磁共振扫描仪上获得的人乳腺癌细胞系皮下异种移植瘤的单像素 P-MR 光谱进行了拟合。我们发现这些肿瘤中 NAD 和 NADH 相对于αATP 的化学位移偏移的变化比正常组织的文献值更大。此外，我们的αATP、NAD 和 NADH 溶液幻影 P-MR 光谱表明，αATP 的化学位移以及 NAD（H）与αATP 之间的偏移与 pH 有关。因此，肿瘤 pH 是否应纳入光谱拟合模型尚需进一步评估。此外，通过优化 P-MRS 方案、增加数据采集时间以及使用更灵敏的线圈进行信号检测，可以提高光谱分辨率和信噪比。
