Iyer M, Barrio J R, Namavari M, Bauer E, Satyamurthy N, Nguyen K, Toyokuni T, Phelps M E, Herschman H R, Gambhir S S
Crump Institute for Molecular Imaging, UCLA/Department of Energy Laboratory of Structural Biology and Molecular Medicine, UCLA-Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California 90095-1770, USA.
J Nucl Med. 2001 Jan;42(1):96-105.
We have synthesized and evaluated 8-[18F]fluoropenciclovir (FPCV) and compared it with 8-[18F]fluoroganciclovir (FGCV) for monitoring the expression of herpes simplex virus type 1 thymidine kinase (HSV1 -tk) reporter gene in cell culture and in vivo.
C6 rat glioma cells stably transfected with HSV1-tk (C6-stb-tk+) and control C6 cells were evaluated for their ability to accumulate FGCV versus FPCV. For in vivo studies, 15 mice were injected by tail vein with increasing levels of an adenoviral vector carrying HSV1-tk. Forty-eight hours later the mice were injected with FPCV and killed 3 h later. The percentage injected dose per gram (%ID/g) liver was then determined. Two additional mice were studied by microPET and autoradiography using FPCV to image adenoviral-mediated hepatic HSV1-tk reporter gene expression. A tumor-bearing mouse (C6 control and C6-stb-tk+) was imaged with FDG, FGCV, and FPCV. Two mice carrying tumors expressing two different reporter genes, HSV1-tk and dopamine type 2 receptor (D2R), were also imaged by microPET using FPCV (day 1) and 3-(2'-[18F]fluoroethyl)spiperone (FESP) (day 2).
FPCV shows a significantly greater accumulation in C6-stb-tk+ cells than does FGCV (P < 0.05). Over identical ranges of adenoviral administration, mouse liver shows a higher %ID/g liver for FPCV (0%-9%) compared with our previously reported results with FGCV (0%-3%). In C6 control and C6-stb-tk+ tumor-bearing mice, FPCV has a greater accumulation than does FGCV for equal levels of HSV1-tk gene expression. In mice carrying tumors expressing either HSV1-tk or D2R reporter genes, there is a corresponding retention of FPCV and FESP, respectively.
These results indicate that FPCV is a better reporter probe than is FGCV for imaging lower levels of HSV1 -tk gene expression in vivo. The results also reveal the ability to monitor the expression of two distinct reporter genes in the same animal using reporter probes specific for each gene.
我们合成并评估了8-[18F]氟喷昔洛韦（FPCV），并将其与8-[18F]氟更昔洛韦（FGCV）进行比较，以监测单纯疱疹病毒1型胸苷激酶（HSV1 -tk）报告基因在细胞培养和体内的表达。
评估稳定转染HSV1-tk的C6大鼠胶质瘤细胞（C6-stb-tk+）和对照C6细胞积累FGCV与FPCV的能力。对于体内研究，15只小鼠经尾静脉注射携带HSV1-tk的腺病毒载体，剂量逐渐增加。48小时后，给小鼠注射FPCV，3小时后处死。然后测定肝脏每克注射剂量百分比（%ID/g）。另外两只小鼠使用FPCV通过微型PET和放射自显影进行研究，以成像腺病毒介导的肝脏HSV1-tk报告基因表达。一只荷瘤小鼠（C6对照和C6-stb-tk+）用FDG、FGCV和FPCV进行成像。两只携带表达两种不同报告基因HSV1-tk和多巴胺2型受体（D2R）肿瘤的小鼠也使用FPCV（第1天）和3-(2'-[18F]氟乙基)螺哌隆（FESP）（第2天）通过微型PET进行成像。
FPCV在C6-stb-tk+细胞中的积累明显高于FGCV（P < 0.05）。在相同的腺病毒给药范围内，与我们之前报道的FGCV结果（0%-3%）相比，小鼠肝脏对FPCV的%ID/g更高（0%-9%）。在C6对照和C6-stb-tk+荷瘤小鼠中，对于相同水平的HSV1-tk基因表达，FPCV的积累高于FGCV。在携带表达HSV1-tk或D2R报告基因肿瘤的小鼠中，分别有相应的FPCV和FESP滞留。
这些结果表明，对于体内较低水平的HSV1 -tk基因表达成像，FPCV是比FGCV更好的报告探针。结果还揭示了使用针对每个基因的报告探针在同一只动物中监测两种不同报告基因表达的能力。
