用放射性标记的单链DNA适体对肌腱蛋白-C进行正电子发射断层显像（PET）。
PET imaging of tenascin-C with a radiolabeled single-stranded DNA aptamer.
作者信息
Jacobson Orit, Yan Xuefeng, Niu Gang, Weiss Ido D, Ma Ying, Szajek Lawrence P, Shen Baozhong, Kiesewetter Dale O, Chen Xiaoyuan
机构信息
Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland.
Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland Department of Radiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
出版信息
J Nucl Med. 2015 Apr;56(4):616-21. doi: 10.2967/jnumed.114.149484. Epub 2015 Feb 19.
UNLABELLED
Tenascin-C is an extracellular matrix glycoprotein that is expressed by injured tissues and by various cancers. Recent publications showed that tenascin-C expression by cancer lesions predicts tumor growth, metastasis, and angiogenesis, suggesting tenascin-C as a potential therapeutic target. Currently there is no noninvasive method to determine tumoral tenascin-C expression in vivo. To address the need for an agent to image and quantify tenascin-C, we report the development of a radioactive PET tracer based on a tenascin-C-specific single-stranded DNA aptamer (tenascin-C aptamer).
METHODS
Tenascin-C aptamer was radiolabeled with (18)F and (64)Cu. PET imaging studies for the evaluation of tumor uptake and pharmacokinetics of tenascin-C aptamer were performed in comparison to a nonspecific scrambled aptamer (Sc aptamer).
RESULTS
The labeled tenascin-C aptamer provided clear visualization of tenascin-C-positive but not tenascin-C-negative tumors. The uptake of tenascin-C aptamer was significantly higher than that of Sc aptamer in tenascin-C-positive tumors. The labeled tenascin-C aptamer had fast clearance from the blood and other nonspecific organs through the kidneys, resulting in high tumor contrast.
CONCLUSION
Our data suggest that suitably labeled tenascin-C aptamer can be used as a PET tracer to image tumor expression of tenascin-C with a high tumor-to-background ratio and might provide insightful and personalized medical data that will help determine appropriate treatment and monitoring.
未标记
腱生蛋白-C是一种细胞外基质糖蛋白，由受损组织和多种癌症表达。最近的出版物表明，癌症病变中腱生蛋白-C的表达可预测肿瘤生长、转移和血管生成，提示腱生蛋白-C作为潜在的治疗靶点。目前尚无在体内确定肿瘤腱生蛋白-C表达的非侵入性方法。为满足对成像和定量腱生蛋白-C的试剂的需求，我们报告了一种基于腱生蛋白-C特异性单链DNA适配体（腱生蛋白-C适配体）的放射性PET示踪剂的研发。
方法
腱生蛋白-C适配体用（18）F和（64）Cu进行放射性标记。与非特异性随机序列适配体（Sc适配体）相比，进行PET成像研究以评估腱生蛋白-C适配体的肿瘤摄取和药代动力学。
结果
标记的腱生蛋白-C适配体可清晰显示腱生蛋白-C阳性而非腱生蛋白-C阴性肿瘤。在腱生蛋白-C阳性肿瘤中，腱生蛋白-C适配体的摄取显著高于Sc适配体。标记的腱生蛋白-C适配体通过肾脏从血液和其他非特异性器官快速清除，从而产生高肿瘤对比度。
结论
我们的数据表明，适当标记的腱生蛋白-C适配体可作为PET示踪剂，以高肿瘤与背景比值成像肿瘤腱生蛋白-C的表达，并可能提供有助于确定适当治疗和监测的有洞察力的个性化医学数据。
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