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

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: Cu-64-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 Cu-64-CHS1 a promising probe for clinical use.