| Title |
In Vivo Intracellular Oxygen Dynamics in Murine Brain Glioma and Immunotherapeutic Response of Cytotoxic T Cells Observed by Fluorine-19 Magnetic Resonance Imaging
|
|---|---|
| Published in |
PLOS ONE, May 2013
|
| DOI | 10.1371/journal.pone.0059479 |
| Pubmed ID | |
| Authors |
Jia Zhong, Masashi Sakaki, Hideho Okada, Eric T. Ahrens |
| Abstract |
Noninvasive biomarkers of anti-tumoral efficacy are of great importance to the development of therapeutic agents. Tumor oxygenation has been shown to be an important indicator of therapeutic response. We report the use of intracellular labeling of tumor cells with perfluorocarbon (PFC) molecules, combined with quantitative ¹⁹F spin-lattice relaxation rate (R₁) measurements, to assay tumor cell oxygen dynamics in situ. In a murine central nervous system (CNS) GL261 glioma model, we visualized the impact of Pmel-1 cytotoxic T cell immunotherapy, delivered intravenously, on intracellular tumor oxygen levels. GL261 glioma cells were labeled ex vivo with PFC and inoculated into the mouse striatum. The R₁ of ¹⁹F labeled cells was measured using localized single-voxel magnetic resonance spectroscopy, and the absolute intracellular partial pressure of oxygen (pO₂) was ascertained. Three days after tumor implantation, mice were treated with 2×10⁷ cytotoxic T cells intravenously. At day five, a transient spike in pO₂ was observed indicating an influx of T cells into the CNS and putative tumor cell apoptosis. Immunohistochemistry and quantitative flow cytometry analysis confirmed that the pO₂ was causally related to the T cells infiltration. Surprisingly, the pO₂ spike was detected even though few (∼4×10⁴) T cells actually ingress into the CNS and with minimal tumor shrinkage. These results indicate the high sensitivity of this approach and its utility as a non-invasive surrogate biomarker of anti-cancer immunotherapeutic response in preclinical models. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 50% |
| Scientists | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 2 | 5% |
| South Africa | 1 | 3% |
| Unknown | 37 | 93% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 12 | 30% |
| Researcher | 8 | 20% |
| Other | 4 | 10% |
| Student > Master | 4 | 10% |
| Student > Bachelor | 3 | 8% |
| Other | 3 | 8% |
| Unknown | 6 | 15% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 10 | 25% |
| Agricultural and Biological Sciences | 5 | 13% |
| Physics and Astronomy | 4 | 10% |
| Chemistry | 3 | 8% |
| Biochemistry, Genetics and Molecular Biology | 2 | 5% |
| Other | 9 | 23% |
| Unknown | 7 | 18% |