Nitriles form mixed-coligand complexes with 99mTc-HYNIC-peptide
Nitriles form mixed-coligand complexes with 99mTc-HYNIC-peptide
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DOI：
10.1016/s0969-8051(01)00278-5
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发表时间：
2002-01-01
影响因子：
3.1
通讯作者：
Hnatowich, DJ
中科院分区：
文献类型：
--
作者：
Liu, GZ;Wescott, C;Hnatowich, DJ
使用12个氨基酸的肽与HYNIC作为模型，我们研究了腈作为可能的共配体标记与Tc-99 m。在使用tricine作为共配体制备Tc-99 m标记的HYNIC-肽之后，通过反相HPLC发现添加乙腈在室温下阻断与乙二胺二乙酸（EDDA）的进一步共配体交换。这种腈的加入改变了Tc-99 m标记肽在正常小鼠中的药代动力学，使其清除速度更快，并且在大多数取样组织中的累积存在显著差异。通过用氰基乙酸酯（HPLC洗脱液中不存在的腈）替代乙腈，可以通过反相HPLC显示存在新的、更亲水的物质。我们的结论是，腈可以作为共配体与Tc-99 m和tricine标记的HYNIC共轭肽。此外，Sep-Pak或HPLC纯化过程中乙腈的存在可能会无意中产生混合的tricine/乙腈coligand Tc-99 m-HYNIC-肽复合物。(C)2002年爱思唯尔科技有限公司All rights reserved.
Using a 12-amino acid peptide conjugated with HYNIC as a model, we investigated nitriles as possible coligands for labeling with Tc-99m. After the preparation of the Tc-99m labeled HYNIC-peptide using tricine as coligand, the addition of acetonitile was found by reverse phase HPLC to block further coligand exchange with ethylenediamine diacetic acid (EDDA) at room temperature. The addition of this nitrile changed the pharmacokinetics of the Tc-99m labeled peptide in normal mice towards faster clearance and significant differences in accumulation in most tissues sampled. By replacing acetonitrile with cyanoacetate, a nitrile not present in the HPLC eluant, it was possible to show the existence of a new, more hydrophilic, species by reverse phase HPLC. We conclude that nitriles can act as coligands for HYNIC-conjugated peptides labeled with Tc-99m and tricine. Furthermore, the presence of acetonitrile during Sep-Pak or HPLC purification may inadvertently generate a mixed tricine/acetonitile coligand Tc-99m-HYNIC-peptide complex. (C) 2002 Elsevier Science Inc. All rights reserved.