Abstract |
Preclinical development of therapeutic agents against cancer could greatly benefit from noninvasive markers of tumor killing. Potentially, the intracellular partial pressure of oxygen (pO(2) ) can be used as an early marker of antitumor efficacy. Here, the feasibility of measuring intracellular pO(2) of central nervous system glioma cells in vivo using (19) F magnetic resonance techniques is examined. Rat 9L glioma cells were labeled with perfluoro-15-crown-5-ether ex vivo and then implanted into the rat striatum. (19) F MRI was used to visualize tumor location in vivo. The mean (19) F T(1) of the implanted cells was measured using localized, single-voxel spectroscopy. The intracellular pO(2) in tumor cells was determined from an in vitro calibration curve. The basal pO(2) of 9L cells (day 3) was determined to be 45.3 ± 5 mmHg (n = 6). Rats were then treated with a 1 × LD10 dose of bischloroethylnitrosourea intravenously and changes in intracellular pO(2) were monitored. The pO(2) increased significantly (P = 0.042, paired T-test) to 141.8 ± 3 mmHg within 18 h after bischloroethylnitrosourea treatment (day 4) and remained elevated (165 ± 24 mmHg) for at least 72 h (day 6). Intracellular localization of the perfluoro-15-crown-5-ether emulsion in 9L cells before and after bischloroethylnitrosourea treatment was confirmed by histological examination and fluorescence microscopy. Overall, noninvasive (19) F magnetic resonance techniques may provide a valuable preclinical tool for monitoring therapeutic response against central nervous system or other deep-seated tumors.
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Authors | Deepak K K Kadayakkara, Jelena M Janjic, Lisa K Pusateri, Won-Bin Young, Eric T Ahrens |
Journal | Magnetic resonance in medicine
(Magn Reson Med)
Vol. 64
Issue 5
Pg. 1252-9
(Nov 2010)
ISSN: 1522-2594 [Electronic] United States |
PMID | 20860007
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2010 Wiley-Liss, Inc. |
Chemical References |
- Antineoplastic Agents, Alkylating
- Biomarkers, Tumor
- Fluorine Radioisotopes
- Radiopharmaceuticals
- Oxygen
|
Topics |
- Animals
- Antineoplastic Agents, Alkylating
(therapeutic use)
- Biomarkers, Tumor
(metabolism)
- Cell Line, Tumor
- Female
- Fluorine Radioisotopes
- Glioma
(diagnosis, drug therapy, metabolism)
- Magnetic Resonance Imaging
(methods)
- Oximetry
(methods)
- Oxygen
(metabolism)
- Radiopharmaceuticals
- Rats
- Rats, Inbred F344
- Staining and Labeling
(methods)
- Treatment Outcome
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