In vivo observation of intracellular oximetry in perfluorocarbon-labeled glioma cells and chemotherapeutic response in the CNS using fluorine-19 MRI.
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.
Kadayakkara
Deepak K K
DK
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.
Janjic
Jelena M
JM
Pusateri
Lisa K
LK
Young
Won-Bin
WB
Ahrens
Eric T
ET
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005462:Fluorine Radioisotopes; D005910:Glioma / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D010092:Oximetry / Q000379:methods*; D010100:Oxygen / Q000378:metabolism*; D019275:Radiopharmaceuticals; D051381:Rats; D011916:Rats, Inbred F344; D013194:Staining and Labeling / Q000379:methods; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D010100:Oxygen