Tumor Microenvironment–Dependent 18F-FDG, 18F-Fluorothymidine, and 18F-Misonidazole Uptake: A Pilot Study in Mouse Models of Human Non–Small Cell Lung Cancer
| Autor: | Huijie Jiang, Tao Huang, Xiaofeng Li, Baozhong Shen, A. Cahid Civelek, Junling Li, Chin K. Ng, Gregory C. Postel |
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| Rok vydání: | 2012 |
| Předmět: |
Oncology
Fluorine Radioisotopes medicine.medical_specialty Lung Neoplasms Pilot Projects Mice Necrosis chemistry.chemical_compound Fluorodeoxyglucose F18 Carcinoma Non-Small-Cell Lung Cell Line Tumor Internal medicine Tumor Microenvironment medicine Animals Humans Pimonidazole Radiology Nuclear Medicine and imaging Proliferation Marker Misonidazole Radioactive Tracers education Lung cancer Cell Proliferation education.field_of_study Tumor microenvironment Chemistry Cancer Biological Transport medicine.disease Cell Hypoxia Dideoxynucleosides Animal euthanasia Disease Models Animal Bromodeoxyuridine Nitroimidazoles Positron-Emission Tomography Cancer cell Cancer research Female |
| Zdroj: | Journal of Nuclear Medicine. 53:1262-1268 |
| ISSN: | 2159-662X 0161-5505 |
| Popis: | (18)F-FDG, (18)F-fluorothymidine, and (18)F-misonidazole PET scans have emerged as important clinical tools in the management of cancer; however, none of them have demonstrated conclusive superiority. The aim of this study was to compare the intratumoral accumulation of (18)F-FDG, (18)F-fluorothymidine, and (18)F-misonidazole and relate this to specific components of the tumor microenvironment in mouse models of human non-small cell lung cancer (NSCLC). Methods We used NSCLC A549 and HTB177 cells to generate subcutaneous and peritoneal xenografts in nude mice. Animals were coinjected with a PET radiotracer, pimonidazole (hypoxia marker), and bromodeoxyuridine (proliferation marker) intravenously 1 h before animal euthanasia. Tumor perfusion was assessed by Hoechst 33342 injection, given 1 min before sacrifice. The intratumoral distribution of PET radiotracers was visualized by digital autoradiography and related to microscopic visualization of proliferation, hypoxia, perfusion, stroma, and necrosis. Results NSCLC xenografts had complex structures with intermingled regions of viable cancer cells, stroma, and necrosis. Cancer cells were either well oxygenated (staining negatively for pimonidazole) and highly proliferative (staining positively for bromodeoxyuridine) or hypoxic (pimonidazole-positive) and noncycling (little bromodeoxyuridine). Hypoxic cancer cells with a low proliferation rate had high(18)F-FDG and (18)F-misonidazole uptake but low (18)F-fluorothymidine accumulation. Well-oxygenated cancer cells with a high proliferation rate accumulated a high level of (18)F-fluorothymidine but low (18)F-FDG and(18)F-misonidazole. Tumor stroma and necrotic zones were always associated with low (18)F-FDG, (18)F-misonidazole, and (18)F-fluorothymidine activity. Conclusion In NSCLC A549 and HTB177 subcutaneously or intraperitoneally growing xenografts, (18)F-fluorothymidine accumulates in well-oxygenated and proliferative cancer cells, whereas (18)F-misonidazole and (18)F-FDG accumulate mostly in poorly proliferative and hypoxic cancer cells. (18)F-FDG and (18)F-misonidazole display similar intratumoral distribution patterns, and both mutually exclude (18)F-fluorothymidine. |
| Databáze: | OpenAIRE |
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