Chien Yi-Chun, Chen John Chun-Hao, Lin Wei-Chan, Ding Hueisch-Jy, Wang Hsin-Ell, Kao Chih-Hao K, Hwang Jeng-Jong
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Bei-tou 11221, Taipei, Taiwan, R.O.C.
Department of Radiology, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.
Oncol Rep. 2014 Aug;32(2):691-9. doi: 10.3892/or.2014.3256. Epub 2014 Jun 12.
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.
1-(2-脱氧-2-[18F]氟-β-D-阿拉伯呋喃糖基)-5-溴尿嘧啶([18F]FBAU)作为胸腺嘧啶的替代物，已被报道为一种有效的报告探针，可通过其正电子发射来追踪细胞代谢。在本研究中，利用携带转染了双报告基因（单纯疱疹病毒1型胸苷激酶(HSV1-tk)和萤火虫荧光素酶(luc)）的F98胶质瘤的大鼠异种移植模型，以[18F]FBAU和D-荧光素酶作为探针，通过多模态分子成像来监测肿瘤进展。用pC1-tk-IRES-luc载体转染大鼠F98胶质瘤细胞。筛选出的稳定克隆重新命名为F98/tk-luc细胞系。使用在左脑接种原位F98/tk-luc胶质瘤的Fischer 344雄性大鼠。在肿瘤接种后第13天，进行生物分布、正电子发射断层扫描(PET)、磁共振成像(MRI)和离体放射自显影。用15 μM更昔洛韦(GCV)处理的F98/tk-luc细胞的存活分数为15.9%，与F98细胞相比，这些细胞中[131I]FIAU的摄取显著增强。在携带F98/tk-luc胶质瘤的大鼠中，肿瘤体积与生物发光的相关系数为0.90。生物分布显示，静脉注射后30、60、90和120分钟时，[18F]FBAU在胶质瘤与正常脑的蓄积比分别为9.16、14.24、5.7和13.7。注射后30 - 90分钟也观察到[18F]FBAU/PET成像中肿瘤持续增强。离体放射自显影也证实肿瘤中有显著的[18F]FBAU摄取。总之，[18F]FBAU可作为PET探针用于监测动物模型中的胶质瘤进展，也可能具有临床应用潜力。
