Morse David L, Raghunand Natarajan, Sadarangani Pooja, Murthi Shiva, Job Constantin, Day Sam, Howison Christine, Gillies Robert J
The University of Arizona, BIO5 Institute, Arizona Cancer Center, Tucson, Arizona 85724, USA.
Magn Reson Med. 2007 Aug;58(2):270-80. doi: 10.1002/mrm.21333.
Choline-containing compounds (CCCs) are elevated in breast cancer, and detected in vivo by the (1)H MRS total choline (tCho) resonance (3.25 ppm) and the (31)P MRS phosphomonoester (PME) resonance (3.8 ppm). Both the tCho and PME resonances decrease early after initiation of successful therapy. The single major component of these composite resonances, phosphocholine (PCho), also responds to therapy by decreasing. The ability to resolve and quantify PCho in vivo would thus increase the sensitivity of this biomarker for early detection of therapeutic response. Herein, the in vivo resolution and quantification of PCho is reported in human mouse xenograft tumors of the human breast cancer cell lines MCF-7 and MDA-mb-231. Significant decreases in tumor PCho are observed within 2 to 4 d posttreatment with the antimicrotubule drug, docetaxel. To determine whether these decreases are a general tumor response or an intracellular metabolic response, high-resolution NMR spectroscopy was performed on extracts of cells treated with docetaxel. Significant decreases in intracellular PCho and increases in glycerophosphocholine (GPC) were observed. These decreases are coincident with other tumor and cellular responses such as tumor growth delay (TGD), cell-cycle arrest, and modes of cell death such as mitotic catastrophe, necrosis, and apoptosis, with mitotic catastrophe predominating.
含胆碱化合物（CCCs）在乳腺癌中含量升高，可通过氢质子磁共振波谱（1H MRS）中的总胆碱（tCho）共振峰（3.25 ppm）和磷磁共振波谱（31P MRS）中的磷酸单酯（PME）共振峰（3.8 ppm）在体内检测到。在成功治疗开始后早期，tCho和PME共振峰均下降。这些复合共振峰的单一主要成分磷酸胆碱（PCho）也会因治疗而下降。因此，在体内解析和定量PCho的能力将提高这种生物标志物对治疗反应早期检测的敏感性。本文报道了在人乳腺癌细胞系MCF-7和MDA-mb-231的人鼠异种移植瘤中PCho的体内解析和定量情况。在用抗微管药物多西他赛治疗后2至4天内，观察到肿瘤PCho显著下降。为了确定这些下降是一般的肿瘤反应还是细胞内代谢反应，对用多西他赛处理的细胞提取物进行了高分辨率核磁共振波谱分析。观察到细胞内PCho显著下降，甘油磷酸胆碱（GPC）增加。这些下降与其他肿瘤和细胞反应如肿瘤生长延迟（TGD）、细胞周期停滞以及细胞死亡模式如有丝分裂灾难、坏死和凋亡同时发生，其中有丝分裂灾难占主导。
