iEDDA Conjugation Reaction in Radiometal Labeling of Peptides with (68)Ga and (64)Cu: Unexpected Findings.
iEDDA Conjugation Reaction in Radiometal Labeling of Peptides with (68)Ga and (64)Cu: Unexpected Findings.
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DOI：
10.1021/acsomega.8b01926
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发表时间：
2018-10-31
期刊：
影响因子：
4.1
通讯作者：
Wängler C
中科院分区：
文献类型：
--
作者：
Litau S;Seibold U;Wängler B;Schirrmacher R;Wängler C
在过去的几年中，反电子需求狄尔斯-阿尔德缀合反应对于抗体的有效体内和离体放射性金属标记变得越来越重要。然而，这种非常快速的反应类型的应用尚未研究放射性标记的肽迄今为止。我们在此显示了3-苄基-1，2，4，5-四嗪-包含（（1，4，7，10-四氮杂环十二烷-4，7，10-三基）三乙酸-1-谷氨酸）（DOTA-GA）和（（1，4，7-三氮杂环壬烷-4，7-二基）二乙酸-1-谷氨酸）（NODA-GA）螯合剂的合成以及它们与68 Ga 3+和64 Cu 2+的放射性金属标记。以高放射化学产率（RCYs）和纯度以及摩尔活性获得二级标记前体68 Ga-DOTA-GA-Tz、68 Ga-NODA-GA-Tz和64 Cu-DOTA-GA-Tz，用于进一步标记反式环辛烯（TCO）修饰的肽。然而，放射性核素标记的四嗪与不同的含TCO的模型肽类似物的以下反应出乎意料地导致形成相当大量的副产物（20-55%），这限制了目标放射性肽的总体可实现的RCY和纯度以及摩尔活性。然而，在其他相同的非放射性反应条件下，无法观察到这种效应。相比之下，相应的一步放射性标记方案提供了目标68 Ga标记的放射性肽，其RCYs非常高，纯度≥99%，摩尔活性为68-72 GBq/μmol，68 Ga的活性为340-358 MBq。因此，用放射性同位素标记的螯合剂-四嗪两步标记TCO修饰的肽的有用性似乎是有限的。
The inverse electron demand Diels–Alder conjugation reaction has gained increasing importance over the past few years for efficient in vivo and ex vivo radiometal labeling of antibodies. However, the application of this very fast reaction type has not been studied for radiolabeling of peptides so far. We show here the synthesis of 3-benzyl-1,2,4,5-tetrazine-comprising ((1,4,7,10-tetraazacyclododecane-4,7,10-triyl)triacetic acid-1-glutaric acid) (DOTA–GA) and ((1,4,7-triazacyclononane-4,7-diyl)diacetic acid-1-glutaric acid) (NODA–GA) chelators and their radiometal labeling with 68Ga3+ and 64Cu2+. The secondary labeling precursors 68Ga–DOTA–GA–Tz, 68Ga–NODA–GA–Tz, and 64Cu–DOTA–GA–Tz were obtained in high radiochemical yields (RCYs) and purities as well as molar activities for further labeling of trans-cyclooctene (TCO)-modified peptides. However, the following reactions of the radiometal-labeled tetrazines with different TCO-comprising model peptide analogs unexpectedly resulted in the formation of a considerable amount of side products (20–55%) which limits the overall achievable RCYs and purities as well as molar activities of the target radiopeptides. Under otherwise identical, nonradioactive reaction conditions, this effect could however not be observed. In contrast, the corresponding one-step radiolabeling protocols provided the target 68Ga-labeled radiopeptides in exceptionally high RCYs and purities of ≥99% and molar activities of 68–72 GBq/μmol starting from activities of 340–358 MBq of 68Ga. Thus, the usefulness of the two-step labeling of TCO-modified peptides with radiometal-labeled chelator-tetrazines seems to be limited.
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影响因子：
3.4
作者：
Seibold, Uwe;Waengler, Bjoern;Waengler, Carmen
通讯作者：
Waengler, Carmen
影响因子：
8.4
作者：
Pandya DN;Bhatt N;Yuan H;Day CS;Ehrmann BM;Wright M;Bierbach U;Wadas TJ
通讯作者：
Wadas TJ
DOI：
10.1007/s00259-011-1768-2
发表时间：
2011-05
影响因子：
9.1
作者：
Lubberink, Mark;Herzog, Hans
通讯作者：
Herzog, Hans
影响因子：
3.1
作者：
Abou DS;Ku T;Smith-Jones PM
通讯作者：
Smith-Jones PM
影响因子：
1.8
作者：
Evans, Helen L.;Carroll, Laurence;Spivey, Alan C.
通讯作者：
Spivey, Alan C.