18F-Fluorothymidine-Pet Imaging of Glioblastoma Multiforme: Effects of Radiation Therapy on Radiotracer Uptake and Molecular Biomarker Patterns
Introduction. PET imaging is a useful clinical tool for studying tumor progression and treatment effects. Conventional 18F-FDG-PET imaging is of limited usefulness for imaging Glioblastoma Multiforme (GBM) due to high levels of glucose uptake by normal brain and the resultant signal-to-noise intensi...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1155/2013/796029 |
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| author | Sanjay Chandrasekaran Andrew Hollander Xiangsheng Xu Joseph L. Benci James J. Davis Jay F. Dorsey Gary Kao |
| author_facet | Sanjay Chandrasekaran Andrew Hollander Xiangsheng Xu Joseph L. Benci James J. Davis Jay F. Dorsey Gary Kao |
| author_sort | Sanjay Chandrasekaran |
| collection | DOAJ |
| description | Introduction. PET imaging is a useful clinical tool for studying tumor progression and treatment effects. Conventional 18F-FDG-PET imaging is of limited usefulness for imaging Glioblastoma Multiforme (GBM) due to high levels of glucose uptake by normal brain and the resultant signal-to-noise intensity. 18F-Fluorothymidine (FLT) in contrast has shown promise for imaging GBM, as thymidine is taken up preferentially by proliferating cells. These studies were undertaken to investigate the effectiveness of 18F-FLT-PET in a GBM mouse model, especially after radiation therapy (RT), and its correlation with useful biomarkers, including proliferation and DNA damage. Methods. Nude/athymic mice with human GBM orthografts were assessed by microPET imaging with 18F-FDG and 18F-FLT. Patterns of tumor PET imaging were then compared to immunohistochemistry and immunofluorescence for markers of proliferation (Ki-67), DNA damage and repair (γH2AX), hypoxia (HIF-1α), and angiogenesis (VEGF). Results. We confirmed that 18F-FLT-PET uptake is limited in healthy mice but enhanced in the intracranial tumors. Our data further demonstrate that 18F-FLT-PET imaging usefully reflects the inhibition of tumor by RT and correlates with changes in biomarker expression. Conclusions. 18F-FLT-PET imaging is a promising tumor imaging modality for GBM, including assessing RT effects and biologically relevant biomarkers. |
| format | Article |
| id | doaj-art-178d33b3c97b4b228ad5f0f5ec12343a |
| institution | Kabale University |
| issn | 1537-744X |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-178d33b3c97b4b228ad5f0f5ec12343a2025-02-03T05:46:48ZengWileyThe Scientific World Journal1537-744X2013-01-01201310.1155/2013/79602979602918F-Fluorothymidine-Pet Imaging of Glioblastoma Multiforme: Effects of Radiation Therapy on Radiotracer Uptake and Molecular Biomarker PatternsSanjay Chandrasekaran0Andrew Hollander1Xiangsheng Xu2Joseph L. Benci3James J. Davis4Jay F. Dorsey5Gary Kao6University of Washington School of Medicine, A-300 Health Sciences Center, Box 356340, Seattle, WA 98195, USADepartment of Radiation Oncology, University of Pennsylvania, 8-087 TRC, 3400 Civic Center Boulevard, Building 421, Philadelphia, PA 19104, USADepartment of Radiation Oncology, University of Pennsylvania, 8-087 TRC, 3400 Civic Center Boulevard, Building 421, Philadelphia, PA 19104, USADepartment of Radiation Oncology, University of Pennsylvania, 8-087 TRC, 3400 Civic Center Boulevard, Building 421, Philadelphia, PA 19104, USADepartment of Radiation Oncology, University of Pennsylvania, 8-087 TRC, 3400 Civic Center Boulevard, Building 421, Philadelphia, PA 19104, USADepartment of Radiation Oncology, University of Pennsylvania, 8-087 TRC, 3400 Civic Center Boulevard, Building 421, Philadelphia, PA 19104, USADepartment of Radiation Oncology, University of Pennsylvania, 8-087 TRC, 3400 Civic Center Boulevard, Building 421, Philadelphia, PA 19104, USAIntroduction. PET imaging is a useful clinical tool for studying tumor progression and treatment effects. Conventional 18F-FDG-PET imaging is of limited usefulness for imaging Glioblastoma Multiforme (GBM) due to high levels of glucose uptake by normal brain and the resultant signal-to-noise intensity. 18F-Fluorothymidine (FLT) in contrast has shown promise for imaging GBM, as thymidine is taken up preferentially by proliferating cells. These studies were undertaken to investigate the effectiveness of 18F-FLT-PET in a GBM mouse model, especially after radiation therapy (RT), and its correlation with useful biomarkers, including proliferation and DNA damage. Methods. Nude/athymic mice with human GBM orthografts were assessed by microPET imaging with 18F-FDG and 18F-FLT. Patterns of tumor PET imaging were then compared to immunohistochemistry and immunofluorescence for markers of proliferation (Ki-67), DNA damage and repair (γH2AX), hypoxia (HIF-1α), and angiogenesis (VEGF). Results. We confirmed that 18F-FLT-PET uptake is limited in healthy mice but enhanced in the intracranial tumors. Our data further demonstrate that 18F-FLT-PET imaging usefully reflects the inhibition of tumor by RT and correlates with changes in biomarker expression. Conclusions. 18F-FLT-PET imaging is a promising tumor imaging modality for GBM, including assessing RT effects and biologically relevant biomarkers.http://dx.doi.org/10.1155/2013/796029 |
| spellingShingle | Sanjay Chandrasekaran Andrew Hollander Xiangsheng Xu Joseph L. Benci James J. Davis Jay F. Dorsey Gary Kao 18F-Fluorothymidine-Pet Imaging of Glioblastoma Multiforme: Effects of Radiation Therapy on Radiotracer Uptake and Molecular Biomarker Patterns The Scientific World Journal |
| title | 18F-Fluorothymidine-Pet Imaging of Glioblastoma Multiforme: Effects of Radiation Therapy on Radiotracer Uptake and Molecular Biomarker Patterns |
| title_full | 18F-Fluorothymidine-Pet Imaging of Glioblastoma Multiforme: Effects of Radiation Therapy on Radiotracer Uptake and Molecular Biomarker Patterns |
| title_fullStr | 18F-Fluorothymidine-Pet Imaging of Glioblastoma Multiforme: Effects of Radiation Therapy on Radiotracer Uptake and Molecular Biomarker Patterns |
| title_full_unstemmed | 18F-Fluorothymidine-Pet Imaging of Glioblastoma Multiforme: Effects of Radiation Therapy on Radiotracer Uptake and Molecular Biomarker Patterns |
| title_short | 18F-Fluorothymidine-Pet Imaging of Glioblastoma Multiforme: Effects of Radiation Therapy on Radiotracer Uptake and Molecular Biomarker Patterns |
| title_sort | 18f fluorothymidine pet imaging of glioblastoma multiforme effects of radiation therapy on radiotracer uptake and molecular biomarker patterns |
| url | http://dx.doi.org/10.1155/2013/796029 |
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