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.