64Cu-Labeled Triphenylphosphonium and Triphenylarsonium Cations as Highly Tumor-Selective Imaging Agents

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• 作者：Jianjun Wang ; Chang-Tong Yang ; Young-Seung Kim ; Subramanya G. Sreerama ; Qizhen Cao ; Zi-Bo Li ; Zhengjie He ; Xiaoyuan Chen ; Shuang Liu
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：October 18, 2007
• 年：2007
• 卷：50
• 期：21
• 页码：5057 - 5069
• 全文大小：385K
• 年卷期：v.50,no.21(October 18, 2007)
• ISSN：1520-4804

文摘

This report presents synthesis and evaluation of the ⁶⁴Cu-labeled triphenylphosphonium (TPP) cations asnew 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 humanglioma xenografts. The most striking difference is that ⁶⁴Cu-L1, ⁶⁴Cu-L2, and ⁶⁴Cu-L3 have much lowerheart uptake (<0.6% ID/g) than ^99mTc-Sestamibi (~18% ID/g) at >30 min p.i. Their tumor/heart ratiosincrease steadily from ~1 at 5 min p.i. to ~5 at 120 min p.i. The tumor/heart ratio of ⁶⁴Cu-L3 is ~40 timesbetter than that of ^99mTc-Sestamibi at 120 min postinjection. Results from in vitro assays show that ⁶⁴Cu-L1is able to localize in tumor mitochondria. The tumor is clearly visualized in the tumor-bearing miceadministered with ⁶⁴Cu-L1 as 30 min postinjection. The ⁶⁴Cu-labeled TPP/TPA cations are very selectiveradiotracers that are able to provide the information of mitochondrial bioenergetic function in tumors bymonitoring mitochondrial potential in a noninvasive fashion.