新型TSPO-PET配体2-(5,7-二乙基-2-(4-(2-[(18)F]氟乙氧基)苯基)吡唑并[1,5-a]嘧啶-3-基)-N,N-二乙酰胺([(18)F]VUIIS1008)在胶质瘤中的临床前影像学评估
Preclinical imaging evaluation of novel TSPO-PET ligand 2-(5,7-Diethyl-2-(4-(2-[(18)F]fluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([ (18)F]VUIIS1008) in glioma.
作者信息
Tang Dewei, Nickels Michael L, Tantawy M Noor, Buck Jason R, Manning H Charles
机构信息
Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, 1161 21st Ave. S., AA 1105 MCN, Nashville, TN, 37232-2310, USA.
出版信息
Mol Imaging Biol. 2014 Dec;16(6):813-20. doi: 10.1007/s11307-014-0743-2.
PURPOSE
Translocator protein (TSPO) concentrations are elevated in glioma, suggesting a role for TSPO positron emission tomography (PET) imaging in this setting. In preclinical PET studies, we evaluated a novel, high-affinity TSPO PET ligand, [(18)F]VUIIS1008, in healthy mice and glioma-bearing rats.
PROCEDURES
Dynamic PET data were acquired simultaneously with [(18)F]VUIIS1008 injection, with binding reversibility and specificity evaluated in vivo by non-radioactive ligand displacement or blocking. Compartmental analysis of PET data was performed using metabolite-corrected arterial input functions. Imaging was validated with histology and immunohistochemistry.
RESULTS
[(18)F]VUIIS1008 exhibited rapid uptake in TSPO-rich organs. PET ligand uptake was displaceable with non-radioactive VUIIS1008 or PBR06 in mice. Tumor accumulation of [(18)F]VUIIS1008 was blocked by pretreatment with VUIIS1008 in rats. [(18)F]VUIIS1008 exhibited improved tumor-to-background ratio and higher binding potential in tumors compared to a structurally similar pyrazolopyrimidine TSPO ligand, [(18)F]DPA-714.
CONCLUSIONS
The PET ligand [(18)F]VUIIS1008 exhibits promising characteristics as a tracer for imaging glioma. Further translational studies appear warranted.
目的
胶质瘤中转位蛋白（TSPO）浓度升高，提示TSPO正电子发射断层扫描（PET）成像在此情况下具有一定作用。在临床前PET研究中，我们在健康小鼠和荷胶质瘤大鼠中评估了一种新型、高亲和力的TSPO PET配体[（18）F]VUIIS1008。
程序
在注射[（18）F]VUIIS1008的同时采集动态PET数据，通过非放射性配体置换或阻断在体内评估结合可逆性和特异性。使用代谢物校正的动脉输入函数对PET数据进行房室分析。通过组织学和免疫组织化学对成像进行验证。
结果
[（18）F]VUIIS1008在富含TSPO的器官中表现出快速摄取。在小鼠中，PET配体摄取可被非放射性VUIIS1008或PBR06置换。在大鼠中，用VUIIS1008预处理可阻断[（18）F]VUIIS1008在肿瘤中的蓄积。与结构相似的吡唑并嘧啶TSPO配体[（18）F]DPA - 714相比，[（18）F]VUIIS1008在肿瘤中表现出改善的肿瘤与背景比值和更高的结合潜力。
结论
PET配体[（18）F]VUIIS1008作为胶质瘤成像示踪剂具有良好的特性。进一步的转化研究似乎是必要的。
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