Design, Synthesis, and Evaluation of a Low-Molecular-Weight 11C-Labeled Tetrazine for Pretargeted PET Imaging Applying Bioorthogonal in Vivo Click Chemistry

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• 作者：Christoph Denk ; Dennis Svatunek ; Severin Mairinger ; Johann Stanek ; Thomas Filip ; Dominik Matscheko ; Claudia Kuntner ; Thomas Wanek ; Hannes Mikula
• 刊名：Bioconjugate Chemistry
• 出版年：2016
• 出版时间：July 20, 2016
• 年：2016
• 卷：27
• 期：7
• 页码：1707-1712
• 全文大小：399K
• 年卷期：0
• ISSN：1520-4812

文摘

A low-molecular-weight tetrazine labeled with the short-lived positron emitter carbon-11 was developed as a bioorthogonal PET probe for pretargeted imaging. A method for efficient and fast synthesis of this imaging agent is presented using radiolabeling of a readily available precursor. High reactivity with trans-cyclooctenes was observed and in vivo investigations including PET/MR scanning showed homogeneous biodistribution, good metabolic stability, and rapid excretion in naive mice. These properties are key to the success of bioorthogonal ¹¹C-PET imaging, which has been shown in a simple pretargeting experiment using TCO-modified mesoporous silica nanoparticles. Overall, this ¹¹C-labeled tetrazine represents a highly versatile and advantageous chemical tool for bioorthogonal PET imaging and enables pretargeting approaches using carbon-11 for the first time.