In vivo detection of small tumour lesions by multi-pinhole SPECT applying a (99m)Tc-labelled nanobody targeting the Epidermal Growth Factor Receptor.
In vivo detection of small tumour lesions by multi-pinhole SPECT applying a (99m)Tc-labelled nanobody targeting the Epidermal Growth Factor Receptor.
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DOI：
10.1038/srep21834
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发表时间：
2016-02-25
影响因子：
4.6
通讯作者：
Alves F
中科院分区：
文献类型：
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作者：
Krüwel T;Nevoltris D;Bode J;Dullin C;Baty D;Chames P;Alves F
在肿瘤发展的早期阶段发现肿瘤，结合对肿瘤标志物如表皮生长因子受体(EGFR)表达的了解，是临床决策的重要前提。在这项研究中，我们应用抗表皮生长因子受体纳米体99mTC-D10通过靶向表皮生长因子受体的人乳腺原位移植瘤模型和皮下人表皮样癌A431小鼠模型，对体积小于100 mm~3的小肿瘤病变进行了可视化研究。使用小至15.5 kDa的纳米体99mTC-D10，能够通过静脉注射后45 分钟已经具有高肿瘤摄取率(3%ID/g)的单光子发射计算机断层成像检测到肿瘤，其肿瘤体积分别为52.5mm3 ± 21.2和26.6mm3 ± 16.7。血清半衰期为4.9 分钟的快速血液清除可产生高的体内对比度和体外肿瘤与血液和组织的比率。相反，在以EGFR表达非常低为特征的MDA-MB-231肿瘤中，没有观察到99mTC-D10的蓄积。在这里，我们展示了在给予抗EGFR纳米体99mTC-D10后不久，通过临床前多针孔SPECT对高表达EGFR的人类小肿瘤的特异性和高对比度的体内可视化。
The detection of tumours in an early phase of tumour development in combination with the knowledge of expression of tumour markers such as epidermal growth factor receptor (EGFR) is an important prerequisite for clinical decisions. In this study we applied the anti-EGFR nanobody 99mTc-D10 for visualizing small tumour lesions with volumes below 100 mm3 by targeting EGFR in orthotopic human mammary MDA-MB-468 and MDA-MB-231 and subcutaneous human epidermoid A431 carcinoma mouse models. Use of nanobody 99mTc-D10 of a size as small as 15.5 kDa enables detection of tumours by single photon emission computed tomography (SPECT) imaging already 45 min post intravenous administration with high tumour uptake (>3% ID/g) in small MDA-MB-468 and A431 tumours, with tumour volumes of 52.5 mm3 ± 21.2 and 26.6 mm3 ± 16.7, respectively. Fast blood clearance with a serum half-life of 4.9 min resulted in high in vivo contrast and ex vivo tumour to blood and tissue ratios. In contrast, no accumulation of 99mTc-D10 in MDA-MB-231 tumours characterized by a very low expression of EGFR was observed. Here we present specific and high contrast in vivo visualization of small human tumours overexpressing EGFR by preclinical multi-pinhole SPECT shortly after administration of anti-EGFR nanobody 99mTc-D10.