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.

Image and motor behavior for monitoring tumor growth in C6 glioma model

“…Both image techniques had good correlation when compared with BLI signal and MRI tumor volume at each time point measured for tumor growth monitoring. Studies about glioma tumor model reported this correlation with excellent results [ 30 – 32 ]. However, this correlation can change at later stages of tumor growth.…”

Validation of Enhancing Effects of Curcumin on Radiotherapy with F98/FGT Glioblastoma-Bearing Rat Model

“…In the pilot rat model, the growth of GBM was successfully followed up with correlated luminescence signal in which the correlation efficiency was about 0.85 [29]. Following their example, in 2014, our team had successfully extended the applications of GBM animal model to a double-reporter gene F98/tk-luc tumor-bearing rat model, whose bioluminescence signals can be accurately detected with multimodality imaging instruments [30]. In that module, the growth of in situ brain tumor was visible and quantitatively followed up with the expressions of luc and HSV1-tk, enlightening the access to examine the feasibility of candidates to serve as GBM drugs and/or radiosensitizers.…”

Application of Genetically Encoded Molecular Imaging Probes in Tumor Imaging

“…Combined genetically encoded molecular imaging probes with nuclear medicine tomography are widely used in tumor imaging, mainly including tracking cell levels, monitoring Contrast Media & Molecular Imaging cancer progression and metastasis, and evaluating the efficacy of anticancer therapy. For example, the herpes simplex virus type 1 thymidine kinase (HSV1-TK) genetic sequence was designed to selectively uptake 18F to locate and track therapeutic substances in glioma [54].…”