Monitoring tumor cell death in murine tumor models using deuterium magnetic resonance spectroscopy and spectroscopic imaging.
Monitoring tumor cell death in murine tumor models using deuterium magnetic resonance spectroscopy and spectroscopic imaging.
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使用氘磁共振光谱和光谱成像监测小鼠肿瘤模型中的肿瘤细胞死亡。
DOI：
10.1073/pnas.2014631118
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发表时间：
2021-03-23
影响因子：
11.1
通讯作者：
Brindle KM
中科院分区：
文献类型：
--
作者：
Hesse F;Somai V;Kreis F;Bulat F;Wright AJ;Brindle KM
对于用于检测体内细胞死亡（例如，在疾病中和在肿瘤治疗后）的灵敏方法存在未满足的临床需求。我们在这里表明，氘磁共振测量在7 T的标记苹果酸生产注射2 H-标记的富马酸盐提供了一个敏感的方法，用于检测治疗后体内肿瘤细胞死亡。苹果酸的产生在活细胞中相对缓慢，但在坏死组织中显著增加。2 H磁共振波谱成像最近已被证明是临床代谢成像的可行技术。我们在这里表明，[2，3 - 2 H2]富马酸盐产生[2，3 - 2 H2]苹果酸的2 H NMR光谱和光谱成像测量可用于通过产生标记的苹果酸来检测体内肿瘤细胞死亡。在用依托泊苷处理的鼠淋巴瘤（EL 4）和用TRAILR 2激动剂处理的人乳腺（MDA-MB-231）和结肠直肠（Colo 205）异种移植物中，在7 T下使用表面线圈定位2 H MR光谱法，测量在向荷瘤小鼠注射[2，3 - 2 H2]富马酸盐（1 g/kg）后[2，3 - 2 H2]苹果酸盐的产生。还使用快速2 H化学位移成像序列对EL 4肿瘤中的苹果酸产生进行成像。药物治疗后48小时，EL 4肿瘤中的苹果酸/富马酸比值从0.016 ± 0.02增加至0.16 ± 0.14（P = 0.0024，n = 3），MDA-MB-231肿瘤从0.019 ± 0.03至0.25 ± 0.23在药物治疗后24 h，Colo 205肿瘤从0.016 ± 0.04降至0.28 ± 0.26（P = 0.0002，n = 5）。这些增加与成像后立即获得的切除肿瘤切片中测量的细胞死亡水平增加相关。[2，3 - 2 H2]富马酸盐产生[2，3 - 2 H2]苹果酸的2 H MR测量提供了一种比超极化[1，4 - 13 C2]富马酸盐代谢的13 C MR测量（先前已用于此目的）更便宜且更灵敏的体内细胞死亡检测方法。
There is an unmet clinical need for sensitive methods for detecting cell death in vivo, for example, in disease and following tumor treatment. We show here that deuterium magnetic resonance measurements at 7 T of labeled malate production from injected 2H-labeled fumarate provide a sensitive method for detecting tumor cell death in vivo following treatment. Malate production was relatively slow in viable cells but was markedly increased in necrotic tissue. 2H magnetic resonance spectroscopic imaging has been shown recently to be a viable technique for metabolic imaging in the clinic. We show here that 2H MR spectroscopy and spectroscopic imaging measurements of [2,3-2H2]malate production from [2,3-2H2]fumarate can be used to detect tumor cell death in vivo via the production of labeled malate. Production of [2,3-2H2]malate, following injection of [2,3-2H2]fumarate (1 g/kg) into tumor-bearing mice, was measured in a murine lymphoma (EL4) treated with etoposide, and in human breast (MDA-MB-231) and colorectal (Colo205) xenografts treated with a TRAILR2 agonist, using surface-coil localized 2H MR spectroscopy at 7 T. Malate production was also imaged in EL4 tumors using a fast 2H chemical shift imaging sequence. The malate/fumarate ratio increased from 0.016 ± 0.02 to 0.16 ± 0.14 in EL4 tumors 48 h after drug treatment (P = 0.0024, n = 3), and from 0.019 ± 0.03 to 0.25 ± 0.23 in MDA-MB-231 tumors (P = 0.0001, n = 5) and from 0.016 ± 0.04 to 0.28 ± 0.26 in Colo205 tumors (P = 0.0002, n = 5) 24 h after drug treatment. These increases were correlated with increased levels of cell death measured in excised tumor sections obtained immediately after imaging. 2H MR measurements of [2,3-2H2]malate production from [2,3-2H2]fumarate provide a potentially less expensive and more sensitive method for detecting cell death in vivo than 13C MR measurements of hyperpolarized [1,4-13C2]fumarate metabolism, which have been used previously for this purpose.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
5.7
作者：
Bohndiek SE;Kettunen MI;Hu DE;Witney TH;Kennedy BW;Gallagher FA;Brindle KM
通讯作者：
Brindle KM
影响因子：
11.2
作者：
Hesketh, Richard L.;Wang, Jiazheng;Brindle, Kevin M.
通讯作者：
Brindle, Kevin M.
影响因子：
2.2
作者：
Garwood, M;DelaBarre, L
通讯作者：
DelaBarre, L
DOI：
10.1073/pnas.1205539109
发表时间：
2012-08-14
影响因子：
11.1
作者：
Clatworthy, Menna R.;Kettunen, Mikko I.;Brindle, Kevin M.
通讯作者：
Brindle, Kevin M.