Enzyme‐Mediated In Situ Self‐Assembly Promotes In Vivo Bioorthogonal Reaction for Pretargeted Multimodality Imaging. (2nd July 2021)

• Record Type: Journal Article
• Authors: Hu, Yuxuan; Zhang, Junya; Miao, Yinxing; Wen, Xidan; Wang, Jian; Sun, Yidan; Chen, Yinfei; Lin, Jianguo; Qiu, Ling; Guo, Kai; Chen, Hong‐Yuan; Ye, Deju
• Is Part Of: Angewandte Chemie. Volume 133:Number 33(2021)
• Page Start: 18230
• Page End: 18241
• Publication Date: 2021-07-02
• Subjects: bioorthogonal reactions -- in vivo imaging -- mulitmodality -- pretargeting -- self-assembly; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202103307
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Pretargeted imaging has emerged as a promising approach to advance nuclear imaging of malignant tumors. Herein, we combine the enzyme‐mediated fluorogenic reaction and in situ self‐assembly with the inverse electron demand Diels–Alder (IEDDA) reaction to develop an activatable pretargeted strategy for multimodality imaging. The trans‐cyclooctene (TCO) bearing small‐molecule probe, P‐FFGd‐TCO, can be activated by alkaline phosphatase and in situ self‐assembles into nanoaggregates (FMNPs‐TCO ) retained on the membranes, permitting to (1) amplify near‐infrared (NIR) fluorescence (FL) and magnetic resonance imaging (MRI) signals, and (2) enrich TCOs to promote IEDDA ligation. The Gallium‐68 ( 68 Ga) labeled tetrazine can readily conjugate the tumor‐retained FMNPs‐TCO to enhance radioactivity uptake in tumors. Strong NIR FL, MRI, and positron emission tomography (PET) signals are concomitantly achieved, allowing for pretargeted multimodality imaging of ALP activity in HeLa tumor‐bearing mice. Abstract : A pretargeted multimodality imaging strategy is based on a combination of the enzyme‐mediated fluorogenic reaction and in situ self‐assembly with the IEDDA reaction. A trans ‐cyclooctene (TCO) bearing a small‐molecule probe is first activated by the target enzyme, leading to in situ self‐assembly and enrichment of the TCOs. This allows subsequent labelling of radioisotopes via the IEDDA reaction, providing NIR FL, MRI and PET signals for in vivo imaging.