Research progress of retinal neurovascular unit injury in glaucoma

Glaucoma is one of the leading causes of vision loss worldwide. More and more studies have suggested that glaucoma is a complicated retinal neurovascular disease. The homeostasis imbalance of retinal neurovascular unit(RNVU)composed of neurons, glial cells and microvascular cells not only induces changes in microvascular structure and glial cells, but also affects the nerve tissue of the retina, resulting in vision loss, which there is no effective treatment to reverse, currently. Exploring the cellular composition and molecular structure of RNVU and investigating the destruction mechanism of normal cellular environment and intercellular connections in glaucoma are of great significance in exploring the pathogenesis and the treatment of glaucoma. The research progress on structural changes and dysfunction of RNVU in glaucoma are reviewed, hoping to provide new ideas for the treatment of glaucoma

New Bifunctional Chelator <i>p</i>‑SCN-PhPr-NE3TA for Copper-64: Synthesis, Peptidomimetic Conjugation, Radiolabeling, and Evaluation for PET Imaging

Bifunctional chelators play an important role in developing metallic radionuclide-based radiopharmaceuticals. In this study, a new bifunctional ligand, <i>p</i>-SCN-PhPr-NE3TA, was synthesized and conjugated to a very late antigen-4 targeting peptidomimetic, LLP2A, for evaluating its application in ⁶⁴Cu-based positron emission tomography (PET) imaging. The new ligand exhibited strong selective coordination of Cu­(II), leading to a robust Cu complex, even in the presence of 10-fold Fe­(III). The LLP2A conjugate of <i>p</i>-SCN-PhPr-NE3TA was prepared and successfully labeled with ⁶⁴Cu under mild conditions. The conjugate ⁶⁴Cu-NE3TA-PEG₄-LLP2A showed significantly higher specific activity, compared with ⁶⁴Cu-NOTA-PEG₄-LLP2A, while maintaining comparable serum stability. Subsequent biodistribution studies and PET imaging in mice bearing B16F10 xenografts confirmed its favorable <i>in vivo</i> performance and high tumor uptake with low background, rendering <i>p</i>-SCN-PhPr-NE3TA a promising bifunctional chelator for ⁶⁴Cu-based radiopharmaceuticals

Universal Molecular Scaffold for Facile Construction of Multivalent and Multimodal Imaging Probes

Multivalent and multimodal imaging probes are rapidly emerging as powerful chemical tools for visualizing various biochemical processes. Herein, we described a bifunctional chelator (BFC)-based scaffold that can be used to construct such promising probes concisely. Compared to other reported similar scaffolds, this new BFC scaffold demonstrated two major advantages: (1) significantly simplified synthesis due to the use of this new BFC that can serve as chelator and linker simultaneously; (2) highly efficient synthesis rendered by using either click chemistry and/or total solid-phase synthesis. In addition, the versatile utility of this molecular scaffold has been demonstrated by constructing several multivalent/multimodal imaging probes labeled with various radioisotopes, and the resulting radiotracers demonstrated substantially improved in vivo performance compared to the two individual monomeric counterparts