title: 18F-fluorothymidine-pet imaging of glioblastoma multiforme: effects of radiation therapy on radiotracer uptake and molecular biomarker patterns.
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.
authors.affiliation: University of Washington School of Medicine, A-300 Health Sciences Center, Seattle, WA 98195, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Chandrasekaran
authors.forename: Andrew
authors.initials: A
authors.lastname: Hollander
authors.forename: Xiangsheng
authors.initials: X
authors.lastname: Xu
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Benci
authors.forename: James J
authors.initials: JJ
authors.lastname: Davis
authors.forename: Jay F
authors.initials: JF
authors.lastname: Dorsey
authors.forename: Gary
authors.initials: G
authors.lastname: Kao
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy*; D006801:Humans; D008657:Metabolic Clearance Rate / Q000528:radiation effects; D051379:Mice; D008819:Mice, Nude; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution / Q000528:radiation effects
chemical_list: D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; C002854:alovudine