Limits...
18F-fluorothymidine-pet imaging of glioblastoma multiforme: effects of radiation therapy on radiotracer uptake and molecular biomarker patterns.

Chandrasekaran S, Hollander A, Xu X, Benci JL, Davis JJ, Dorsey JF, Kao G - ScientificWorldJournal (2013)

Bottom Line: Conventional (18)F-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. (18)F-Fluorothymidine (FLT) in contrast has shown promise for imaging GBM, as thymidine is taken up preferentially by proliferating cells.Results.Conclusions. (18)F-FLT-PET imaging is a promising tumor imaging modality for GBM, including assessing RT effects and biologically relevant biomarkers.

View Article: PubMed Central - PubMed

Affiliation: University of Washington School of Medicine, A-300 Health Sciences Center, Seattle, WA 98195, USA.

ABSTRACT
Introduction. PET imaging is a useful clinical tool for studying tumor progression and treatment effects. Conventional (18)F-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. (18)F-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 (18)F-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 (18)F-FDG and (18)F-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 (18)F-FLT-PET uptake is limited in healthy mice but enhanced in the intracranial tumors. Our data further demonstrate that (18)F-FLT-PET imaging usefully reflects the inhibition of tumor by RT and correlates with changes in biomarker expression. Conclusions. (18)F-FLT-PET imaging is a promising tumor imaging modality for GBM, including assessing RT effects and biologically relevant biomarkers.

Show MeSH

Related in: MedlinePlus

Radiation therapy leads to profound growth inhibition of flank tumors. (a) BLI of bilateral flank xenografts at 0, 5, 12, and 20 days following unilateral 16 gray (Gy) radiation therapy (RT). Reduced surface radiance noted in RT tumors. (b) Comparison of changes in BLI Fluxmax⁡ values in control (n = 3) and RT (n = 3) tumors. Reductions in Fluxmax⁡ seen by 5 days after RT. (c) Comparison of change in %ID of 18F-FLT uptake in RT versus control tumors (n = 2) before RT and 2 weeks after RT. RT tumors demonstrate decreased uptake at 2 weeks.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3649687&req=5

fig3: Radiation therapy leads to profound growth inhibition of flank tumors. (a) BLI of bilateral flank xenografts at 0, 5, 12, and 20 days following unilateral 16 gray (Gy) radiation therapy (RT). Reduced surface radiance noted in RT tumors. (b) Comparison of changes in BLI Fluxmax⁡ values in control (n = 3) and RT (n = 3) tumors. Reductions in Fluxmax⁡ seen by 5 days after RT. (c) Comparison of change in %ID of 18F-FLT uptake in RT versus control tumors (n = 2) before RT and 2 weeks after RT. RT tumors demonstrate decreased uptake at 2 weeks.

Mentions: Experimental mice (n = 3) with bilateral U251-GFP-LUC flank tumors were exposed to a single unilateral fraction of 16 Gy RT to the right side flank tumor and tumor growth of the irradiated and control nonirradiated tumors was subsequently followed serially with BLI (Figure 3(a)). Fluxmax⁡ in control tumors progressively increased in the weeks following radiation, while RT tumors demonstrated reduction in BLI starting after 1 week (Figure 3(b)).


18F-fluorothymidine-pet imaging of glioblastoma multiforme: effects of radiation therapy on radiotracer uptake and molecular biomarker patterns.

Chandrasekaran S, Hollander A, Xu X, Benci JL, Davis JJ, Dorsey JF, Kao G - ScientificWorldJournal (2013)

Radiation therapy leads to profound growth inhibition of flank tumors. (a) BLI of bilateral flank xenografts at 0, 5, 12, and 20 days following unilateral 16 gray (Gy) radiation therapy (RT). Reduced surface radiance noted in RT tumors. (b) Comparison of changes in BLI Fluxmax⁡ values in control (n = 3) and RT (n = 3) tumors. Reductions in Fluxmax⁡ seen by 5 days after RT. (c) Comparison of change in %ID of 18F-FLT uptake in RT versus control tumors (n = 2) before RT and 2 weeks after RT. RT tumors demonstrate decreased uptake at 2 weeks.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3649687&req=5

fig3: Radiation therapy leads to profound growth inhibition of flank tumors. (a) BLI of bilateral flank xenografts at 0, 5, 12, and 20 days following unilateral 16 gray (Gy) radiation therapy (RT). Reduced surface radiance noted in RT tumors. (b) Comparison of changes in BLI Fluxmax⁡ values in control (n = 3) and RT (n = 3) tumors. Reductions in Fluxmax⁡ seen by 5 days after RT. (c) Comparison of change in %ID of 18F-FLT uptake in RT versus control tumors (n = 2) before RT and 2 weeks after RT. RT tumors demonstrate decreased uptake at 2 weeks.
Mentions: Experimental mice (n = 3) with bilateral U251-GFP-LUC flank tumors were exposed to a single unilateral fraction of 16 Gy RT to the right side flank tumor and tumor growth of the irradiated and control nonirradiated tumors was subsequently followed serially with BLI (Figure 3(a)). Fluxmax⁡ in control tumors progressively increased in the weeks following radiation, while RT tumors demonstrated reduction in BLI starting after 1 week (Figure 3(b)).

Bottom Line: Conventional (18)F-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. (18)F-Fluorothymidine (FLT) in contrast has shown promise for imaging GBM, as thymidine is taken up preferentially by proliferating cells.Results.Conclusions. (18)F-FLT-PET imaging is a promising tumor imaging modality for GBM, including assessing RT effects and biologically relevant biomarkers.

View Article: PubMed Central - PubMed

Affiliation: University of Washington School of Medicine, A-300 Health Sciences Center, Seattle, WA 98195, USA.

ABSTRACT
Introduction. PET imaging is a useful clinical tool for studying tumor progression and treatment effects. Conventional (18)F-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. (18)F-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 (18)F-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 (18)F-FDG and (18)F-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 (18)F-FLT-PET uptake is limited in healthy mice but enhanced in the intracranial tumors. Our data further demonstrate that (18)F-FLT-PET imaging usefully reflects the inhibition of tumor by RT and correlates with changes in biomarker expression. Conclusions. (18)F-FLT-PET imaging is a promising tumor imaging modality for GBM, including assessing RT effects and biologically relevant biomarkers.

Show MeSH
Related in: MedlinePlus