Measurement of the rate of copper(II) exchange for 64Cu complexes of bifunctional chelators
Measurement of the rate of copper(II) exchange for 64Cu complexes of bifunctional chelators
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DOI：
10.1016/j.ica.2012.07.012
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发表时间：
2012-12-01
影响因子：
2.8
通讯作者：
Packard, Alan B.
中科院分区：
文献类型：
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作者：
Maheshwari, Vidhi;Dearling, Jason L. J.;Packard, Alan B.
测量Cu-64从用于制备Cu-64标记蛋白质的螯合剂中的损失速率对于开发有效的Cu-64标记放射性药物是至关重要的。然而，通常情况下，该评估是间接进行的，通过比较标记蛋白在肝脏中的相对摄取，或在非生理条件下，如热5 M HCl。在本研究中，我们测量了一系列螯合剂（DOTA，TETA和NOTA）中Cu-64的损失率，这些螯合剂通常用于标记蛋白质作为[Cu 2 +]（1，2和5 μ M）和pH（7.5，6.0）的函数。5.0）。我们发现Cu-64-NOTA比Cu-64-TETA在某种程度上更动力学稳定，并且Cu-64-NOTA和Cu-64-TETA都比Cu-64-DOTA更动力学稳定。此外，Cu-64从Cu-DOTA的损失率随着[Cu 2 +]和pH的升高而增加，而Cu-64从Cu-TETA和Cu-NOTA的损失率最小程度地依赖于[Cu 2 +]和pH。这些结果表明，NOTA优选于TETA和DOTA用于制备Cu-64标记的蛋白质。(C)2012 Elsevier B. V.保留所有权利。
Measurement of the rate of loss of Cu-64 from the chelators used in the preparation of Cu-64-labeled proteins is critical to the development of effective Cu-64-labeled radiopharmaceuticals. Typically, however, this assessment has been made indirectly, by comparison of the relative uptake of the labeled proteins in the liver, or under non-physiological conditions such as hot 5 M HCl. In the present study, we measured the rate of loss of Cu-64 from a series of chelators (DOTA, TETA, and NOTA) that are commonly used to label proteins as a function of [Cu2+] (1, 2, and 5 mu M) and pH (7.5, 6.0. and 5.0). We found that Cu-64-NOTA is somewhat more kinetically stable than Cu-64-TETA and that both Cu-64-NOTA and Cu-64-TETA are much more kinetically stable than Cu-64-DOTA. Furthermore, the rate of loss of Cu-64 from Cu-DOTA increased with higher [Cu2+] and pH while the rate of loss of Cu-64 from Cu-TETA and Cu-NOTA was minimally dependent on [Cu2+] and pH. These results suggest that NOTA is preferable to TETA and DOTA for the preparation of Cu-64-labeled proteins. (C) 2012 Elsevier B.V. All rights reserved.