Strained Cyclooctyne as a Molecular Platform for Construction of Multimodal Imaging Probes

• Published in: Angewandte Chemie (International ed.) Vol. 54; no. 20; pp. 5981 - 5984
• Main Authors: Sun, Yao, Ma, Xiaowei, Cheng, Kai, Wu, Biying, Duan, Jianli, Chen, Hao, Bu, Lihong, Zhang, Ruiping, Hu, Xianming, Deng, Zixin, Xing, Lei, Hong, Xuechuan, Cheng, Zhen
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 11.05.2015; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: alkynes; Alkynes - chemistry; Alkynes - pharmacokinetics; Animals; Assembly; Biomedical research; Cell Line, Tumor; Chemistry; Chemistry, Multidisciplinary; Cyclooctanes - chemistry; Cyclooctanes - pharmacokinetics; Disease Models, Animal; fluorescence; Humans; Imaging; imaging agents; Mice; Molecular Imaging; Molecular Probes - chemistry; Molecular Probes - pharmacokinetics; Molecular Structure; Neoplasms, Experimental - diagnosis; Physical Sciences; Platforms; Positron emission; Positron-Emission Tomography; Science & Technology; strained molecules; Sulfhydryl Compounds - chemistry; Sulfhydryl Compounds - pharmacokinetics; thiols; Tomography; Translations; Tumors; Uptakes; strained molecules; fluorescence; alkynes; CHEMISTRY; CHEMICAL-BIOLOGY; CHELATOR; imaging agents; thiols; PLASMINOGEN-ACTIVATOR RECEPTOR; EXPRESSION; PET; PEPTIDE
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201500941

Small‐molecule‐based multimodal and multifunctional imaging probes play prominent roles in biomedical research and have high clinical translation ability. A novel multimodal imaging platform using base‐catalyzed double addition of thiols to a strained internal alkyne such as bicyclo[6.1.0]nonyne has been established in this study, thus allowing highly selective assembly of various functional units in a protecting‐group‐free manner. Using this molecular platform, novel dual‐modality (PET and NIRF) uPAR‐targeted imaging probe: 64Cu‐CHS1 was prepared and evaluated in U87MG cells and tumor‐bearing mice models. The excellent PET/NIRF imaging characteristics such as good tumor uptake (3.69 %ID/g at 2 h post‐injection), high tumor contrast, and specificity were achieved in the small‐animal models. These attractive imaging properties make 64Cu‐CHS1 a promising probe for clinical use. Spitting image: The products of the base‐catalyzed addition of various functional molecules to bicyclo[6.1.0]nonyne‐based scaffolds provided precursors for novel dual‐modality (PET and NIRF) uPAR‐targeted imaging probes. The probes were evaluated in U87MG cells and tumor‐bearing mice models, thus demonstrating excellent imaging characteristics.