Wang Jianjun, Yang Chang-Tong, Kim Young-Seung, Sreerama Subramanya G, Cao Qizhen, Li Zi-Bo, He Zhengjie, Chen Xiaoyuan, Liu Shuang
School of Health Sciences, Purdue University, West Lafayette, Indiana, USA.
J Med Chem. 2007 Oct 18;50(21):5057-69. doi: 10.1021/jm0704088. Epub 2007 Sep 15.
This report presents synthesis and evaluation of the 64Cu-labeled triphenylphosphonium (TPP) cations as new radiotracers for imaging tumors by positron emission tomography. Biodistribution properties of 64Cu-L1, 64Cu-L2, 64Cu-L3, and 99mTc-Sestamibi were evaluated in athymic nude mice bearing U87MG human glioma xenografts. The most striking difference is that 64Cu-L1, 64Cu-L2, and 64Cu-L3 have much lower heart uptake (<0.6% ID/g) than 99mTc-Sestamibi ( approximately 18% ID/g) at >30 min p.i. Their tumor/heart ratios increase steadily from approximately 1 at 5 min p.i. to approximately 5 at 120 min p.i. The tumor/heart ratio of 64Cu-L3 is approximately 40 times better than that of 99mTc-Sestamibi at 120 min postinjection. Results from in vitro assays show that 64Cu-L1 is able to localize in tumor mitochondria. The tumor is clearly visualized in the tumor-bearing mice administered with 64Cu-L1 as 30 min postinjection. The 64Cu-labeled TPP/TPA cations are very selective radiotracers that are able to provide the information of mitochondrial bioenergetic function in tumors by monitoring mitochondrial potential in a noninvasive fashion.
本报告介绍了64Cu标记的三苯基鏻（TPP）阳离子作为正电子发射断层扫描成像肿瘤的新型放射性示踪剂的合成与评估。在携带U87MG人胶质瘤异种移植瘤的无胸腺裸鼠中评估了64Cu-L1、64Cu-L2、64Cu-L3和99mTc-司他比的生物分布特性。最显著的差异是，注射后>30分钟时，64Cu-L1、64Cu-L2和64Cu-L3的心脏摄取（<0.6%ID/g）远低于99mTc-司他比（约18%ID/g）。它们的肿瘤/心脏比值从注射后5分钟时的约1稳步增加到注射后120分钟时的约5。注射后120分钟时，64Cu-L3的肿瘤/心脏比值比99mTc-司他比约好40倍。体外试验结果表明，64Cu-L1能够定位于肿瘤线粒体。注射64Cu-L1后30分钟，在荷瘤小鼠中肿瘤清晰可见。64Cu标记的TPP/TPA阳离子是非常有选择性的放射性示踪剂，能够通过以非侵入性方式监测线粒体电位来提供肿瘤中线粒体生物能量功能的信息。
