期刊
MAGNETIC RESONANCE IN MEDICINE
卷 54, 期 1, 页码 43-50出版社
WILEY
DOI: 10.1002/mrm.20529
关键词
apoptosis detection; lipid accumulation; in vivo MRS; tumors; chemotherapy
Proton MRS detection of cellular lipid accumulation has been suggested as a noninvasive method for detecting apoptosis or programmed cell death (PCD) in vivo. The spectral changes that have been observed in apoptotic cells include a general increase in lipid signals and a specific increase in the ratio of the lipid methylene-to-methyl peak intensities. These changes were investigated here following drug-induced apoptosis, both in vitro with a murine lymphoma cell line (EL-4) and in vivo following implantation of these cells to form subcutaneous tumors. Fluorescence microscopy and flow cytometric measurements with a lipophilic dye revealed an accumulation of cytoplasmic lipid droplets in isolated EL-4 cells undergoing etoposide-induced apoptosis. H-1 MR spectra (both diffusion-weighted (DW) and unweighted) showed an increase in lipid signals. However, the methylene/methyl peak ratio showed only minimal changes. Localized in vivo spectroscopy of EL-4 tumors also showed an increase in lipid signals, including a signal from polyunsaturated lipid at 2.8 ppm, after 16-24 h of drug treatment. Again there was no significant change in the methylene/methyl peak ratio. This study confirms that MRS-detectable lipids accumulate in tumor cells undergoing apoptosis, and therefore may be usable as a marker for the noninvasive detection of tumor cell apoptosis in the clinic. (c) 2005 Wiley-Liss, Inc.
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