Alauddin Mian M, Shahinian Atranik, Gordon Erlinda M, Conti Peter S
University of Southern California, USA.
Mol Imaging. 2002 Apr-Jun;1(2):74-81. doi: 10.1162/15353500200202100.
2'-Deoxy-2'-flouro-5-methyl-1-beta-D-arabinofuranosyluracil (FMAU) has been evaluated in HT-29 cells as a potential positron emission tomography (PET) radiotracer for imaging HSV-tk gene expression in vivo. In vitro experiments demonstrate that the accumulation of [14C]-FMAU in HSV-tk-expressing cells is 2.4-fold (p < .02), 4.0-fold (p < .001), and 5.3-fold (p < .001) higher than the wild-type cells at 1, 3, and 5 hr, respectively. In vivo studies revealed that the tumor uptake in HSV-tk-expressing cells was 2.3-fold (p < .001), 3.0-fold (p < .001), and 5.5-fold (p < .001) higher than the control cells at 1, 2, and 5 hr, respectively. FMAU was found to be more sensitive compared to our earlier studies using 9-[(3-18F-fluoro-1-hydroxy-2-propoxy)methyl]-guanine ([18F]-FHPG) and 9-(4-[18F]-fluoro-3-hydroxy-methylbutyl)guanine ([18F]-FHBG) in the same cell lines, although, the specificity was less than FHBG. These results suggest that while FMAU labeled with PET isotopes may be useful for imaging HSV-tk-expressing tumors in vivo, multitracer studies across additional tumor models are necessary in order to identify an optimal PET radiotracer.
2'-脱氧-2'-氟-5-甲基-1-β-D-阿拉伯呋喃糖基尿嘧啶（FMAU）已在HT-29细胞中作为一种潜在的正电子发射断层扫描（PET）放射性示踪剂进行评估，用于体内成像单纯疱疹病毒胸苷激酶（HSV-tk）基因表达。体外实验表明，在1、3和5小时时，表达HSV-tk的细胞中[14C]-FMAU的积累分别比野生型细胞高2.4倍（p < 0.02）、4.0倍（p < 0.001）和5.3倍（p < 0.001）。体内研究显示，在1、2和5小时时，表达HSV-tk的细胞中的肿瘤摄取分别比对照细胞高2.3倍（p < 0.001）、3.0倍（p < 0.001）和5.5倍（p < 0.001）。与我们早期在相同细胞系中使用9-[(3-18F-氟-1-羟基-2-丙氧基)甲基]-鸟嘌呤（[18F]-FHPG）和9-(4-[18F]-氟-3-羟基甲基丁基)鸟嘌呤（[18F]-FHBG）的研究相比，发现FMAU更敏感，尽管其特异性低于FHBG。这些结果表明，虽然用PET同位素标记的FMAU可能有助于体内成像表达HSV-tk的肿瘤，但为了确定最佳的PET放射性示踪剂，有必要在更多肿瘤模型中进行多示踪剂研究。
