title: Using [¹⁸F]FBAU for imaging brain tumor progression in an F98/tk-luc glioma-bearing rat model.
abstract: 1-(2-Deoxy-2-[18F]fluoro-β-D-arabinofuranosyl)-5-bromouracil ([18F]FBAU), a substitute for thymine, has been reported as an effective reporter probe by which to trace cellular metabolism with its positron emission. In the present study, a rat xenograft model bearing F98 glioma transfected with dual reporter genes, herpes simplex virus type 1 thymidine kinase (HSV1-tk) and firefly luciferase (luc) was used for monitoring tumor progression by multimodalities of molecular imaging using [18F]FBAU and D-luciferase as probes. Rat F98 glioma cells were transfected with the pC1-tk-IRES-luc vectors. The selected stable clone was renamed as the F98/tk-luc cell line. Fischer 344 male rats bearing orthotropic F98/tk-luc gliomas in the left brain were used. On day 13 post tumor inoculation, biodistribution, positron emission tomography (PET), magnetic resonance imaging (MRI) and ex vivo autoradiography were performed. The surviving fraction of F98/tk-luc cells treated with 15 µM ganciclovir (GCV) was 15.9%, and the uptake of [131I]FIAU in these cells was significantly enhanced when compared with F98 cells. The correlation coefficient of tumor volume vs. the bioluminescence in the F98/tk-luc glioma-bearing rats was 0.90. The biodistribution showed that the accumulation ratios of [18F]FBAU for glioma-to-normal brain were 9.16, 14.24, 5.7 and 13.7 at 30, 60, 90 and 120 min post i.v. injection, respectively. Consistent tumor enhancement of [18F]FBAU/PET imaging was also noted from 30-90 min post injection. Ex vivo autoradiography also confirmed significant [18F]FBAU uptake in tumors. In conclusion, [18F]FBAU may be used as a PET probe for monitoring glioma progression in animal models and may have potential for clinical use as well.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Bei-tou 11221, Taipei, Taiwan, R.O.C.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Chien
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Bei-tou 11221, Taipei, Taiwan, R.O.C.
authors.forename: John Chun-Hao
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Department of Radiology, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.
authors.forename: Wei-Chan
authors.initials: WC
authors.lastname: Lin
authors.affiliation: Department of Medical Imaging and Radiological Sciences, I-Shou University, Jiaosu Village, Kaohsiung 82445, Taiwan, R.O.C.
authors.forename: Hueisch-Jy
authors.initials: HJ
authors.lastname: Ding
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Bei-tou 11221, Taipei, Taiwan, R.O.C.
authors.forename: Hsin-Ell
authors.initials: HE
authors.lastname: Wang
authors.affiliation: Department of Radiopharmaceutical Production, Buddhist Tzu Chi General Hospital, Hualien 97002, Taiwan, R.O.C.
authors.forename: Chih-Hao K
authors.initials: CH
authors.lastname: Kao
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Bei-tou 11221, Taipei, Taiwan, R.O.C.
authors.forename: Jeng-Jong
authors.initials: JJ
authors.lastname: Hwang
mesh_terms: D000818:Animals; D001976:Bromouracil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D005910:Glioma / Q000175:diagnosis / Q000000981:diagnostic imaging*; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D009374:Neoplasms, Experimental; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D013937:Thymidine Kinase / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: C470854:1-(2-fluoro-2-deoxyarabinofuranosyl)-5-bromouracil; D019275:Radiopharmaceuticals; D014764:Viral Proteins; D001976:Bromouracil; D013937:Thymidine Kinase