Tetrazine-trans-cyclooctene ligation for the rapid construction of integrin αvβ3 targeted PET tracer based on a cyclic RGD peptide

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Selvaraj, Ramajeyam¹  Liu, Shuanglong²  Hassink, Matthew¹  Huang, Chiun-wei²  Yap, Li-peng²  Park, Ryan²  Fox, Joseph M.¹  Li, Zibo²  Conti, Peter S.² 

[1] Univ Delaware, Dept Chem & Biochem, Brown Labs, Newark, DE 19803 USA

[2] Univ So Calif, Dept Radiol, Mol Imaging Ctr, Los Angeles, CA 90033 USA

关键词: Tetrazine-trans-cyclooctene ligation;    Integrin alpha(v)beta(3);    Positron emission tomography (PET);    RGD peptide;    Fluorine-18;   

DOI  :  10.1016/j.bmcl.2011.04.116

来源: Elsevier

【 摘 要 】

Labeling biomolecules with F-18 is usually done through coupling with prosthetic groups, which generally requires several time-consuming radiosynthetic steps resulting in low labeling yield. Recently, the tetrazine-trans-cyclooctene ligation has been introduced as a method of bioconjugation that proceeds with fast reaction rates without need for catalysis. Herein, we report the development of an extremely fast and efficient method for generating F-18 labeled probes based on the tetrazine-trans-cyclooctene ligation. Starting with only 30 mu g (78 mu M) of a tetrazine-RGD conjugate and 2 mCi (5 mu M) of F-18-trans-cyclooctene, the F-18 labeled RGD peptide could be obtained in more than 90% yield within five minutes. The F-18 labeled RGD peptide demonstrated prominent tumor uptake in vivo. The receptor specificity was confirmed by blocking experiments. These results successfully demonstrate that the tetrazine-trans-cyclooctene ligation serves as an efficient labeling method for PET probe construction. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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