PET Imaging of Tumor Neovascularization in a Transgenic Mouse Model with a Novel 64Cu-DOTA-Knottin Peptide
PET Imaging of Tumor Neovascularization in a Transgenic Mouse Model with a Novel 64Cu-DOTA-Knottin Peptide
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DOI：
10.1158/0008-5472.can-10-1338
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发表时间：
2010-11-15
期刊：
影响因子：
11.2
通讯作者：
Gambhir, Sanjiv S.
中科院分区：
文献类型：
--
作者：
Nielsen, Carsten H.;Kimura, Richard H.;Gambhir, Sanjiv S.
由于肺癌的高死亡率，迫切需要开发能够在可治愈阶段早期检测疾病的诊断程序。靶向分子成像建立在正电子发射断层扫描/计算机断层扫描（PET/CT）的积极属性上，可以对较小的肺结节进行无创检测和表征，从而增加积极治疗结果的机会。在这项研究中，我们调查的能力，表征肺肿瘤自发出现在转基因小鼠模型。首先用小动物CT鉴定肿瘤，然后使用小动物PET用新型Cu-64- 1，4，7，10-四氮杂十二烷-N，N ′，N ″，N ″-四乙酸（DOTA）-结蛋白肽进行表征，所述结蛋白肽靶向在肿瘤相关的新血管系统上的血管生成期间上调的整联蛋白。用knottin肽获得的成像结果与标准F-18-氟脱氧葡萄糖（FDG）PET小动物成像进行比较。通过小动物CT在转基因小鼠中成功鉴定了直径小至3 mm的肺结节，Cu-64-DOTA-knottin 2.5F和FDG都能够将肺结节与周围组织区分开。肺肿瘤中Cu-64-DOTA-knottin 2.5F示踪剂的摄取和保留结合胸腔中的低背景导致与FDG相比统计学上更高的肿瘤与背景（正常肺）比率（6.01 +/- 0.61对4.36 +/- 0.68; P < 0.05）。离体生物分布显示Cu-64-DOTA-结蛋白2.5F具有快速的肾清除率，同时在胸腔中具有低的非特异性蓄积。总的来说，这些结果表明Cu-64-DOTA-knottin 2.5F是用于肺癌的早期检测和改进表征的临床转化的有希望的候选物。Cancer Res; 70（22）; 9022-30. (C)2010年AACR。
Due to the high mortality of lung cancer, there is a critical need to develop diagnostic procedures enabling early detection of the disease while at a curable stage. Targeted molecular imaging builds on the positive attributes of positron emission tomography/computed tomography (PET/CT) to allow for a noninvasive detection and characterization of smaller lung nodules, thus increasing the chances of positive treatment outcome. In this study, we investigate the ability to characterize lung tumors that spontaneously arise in a transgenic mouse model. The tumors are first identified with small animal CT followed by characterization with the use of small animal PET with a novel Cu-64-1,4,7,10-tetra-azacylododecane-N, N', N '' N'''-tetraacetic acid (DOTA)-knottin peptide that targets integrins upregulated during angiogenesis on the tumor associated neovasculature. The imaging results obtained with the knottin peptide are compared with standard F-18-fluorodeoxyglucose (FDG) PET small animal imaging. Lung nodules as small as 3 mm in diameter were successfully identified in the transgenic mice by small animal CT, and both Cu-64-DOTA-knottin 2.5F and FDG were able to differentiate lung nodules from the surrounding tissues. Uptake and retention of the Cu-64-DOTA-knottin 2.5F tracer in the lung tumors combined with a low background in the thorax resulted in a statistically higher tumor to background (normal lung) ratio compared with FDG (6.01 +/- 0.61 versus 4.36 +/- 0.68; P < 0.05). Ex vivo biodistribution showed Cu-64-DOTA-knottin 2.5F to have a fast renal clearance combined with low nonspecific accumulation in the thorax. Collectively, these results show Cu-64-DOTA-knottin 2.5F to be a promising candidate for clinical translation for earlier detection and improved characterization of lung cancer. Cancer Res; 70(22); 9022-30. (C) 2010 AACR.