Artificial tumor model suitable for monitoring 31 P and 13 C NMR spectroscopic changes during chemotherapy‐induced apoptosis in human glioma cells

• Published in: Magnetic resonance in medicine Vol. 54; no. 1; pp. 67 - 78
• Main Authors: Mancuso, Anthony, Zhu, Aizhi, Beardsley, Nancy J., Glickson, Jerry D., Wehrli, Suzanne, Pickup, Stephen
• Format: Journal Article
• Language: English
• Published: 01.07.2005
• ISSN: 0740-3194; 1522-2594
• DOI: 10.1002/mrm.20545

Abstract An artificial tumor method was developed to study cells inside the sensitive volume of an NMR spectrometer during growth and apoptosis. The tumor was composed of a 50:50 mixture of tightly packed porous‐collagen and nonporous‐polystyrene microspheres. The porous collagen served as a growth surface for the tumor cells, and the nonporous polystyrene served as a structural support to limit compression of the packed bed during perfusion. The microspheres were held between two porous polyethylene discs that were tightly sealed inside the NMR perfusion chamber. The new method was evaluated with two cell types: a mouse mammary tumor line (EMT6/SF) and a human glioma line (SF188). The results indicate that for both lines, ∼10 9 metabolically active cells could be sustained for at least 1 week in the 12‐cm 3 artificial tumor. Further, cells undergoing chemotherapy‐induced apoptosis (which is known to cause detachment of cells from their surroundings) were retained in the artificial tumor. In preliminary 31 P NMR studies, glioma cells treated with temozolomide (TMZ) exhibited reduced phosphocholine (PCh) levels relative to glycerophosphocholine (GPC) and diphosphodiester (DPDE) levels. They also exhibited sharply reduced oxygen consumption and TCA cycle 13 C labeling, while they retained glycolytic activity. These metabolic changes are consistent with those that would be expected during mitochondrially‐mediated apoptosis. Magn Reson Med 54:67–78, 2005. © 2005 Wiley‐Liss, Inc.