Molecular imaging based on target-enabled in situ ligand aggregation for monitoring therapeutic responses in vivo
Abstract/Contents
- Abstract
- In the era of precision medicine, there is a growing demand for new companion diagnostics that can be used for monitoring therapeutic responses. These companion diagnostics can guide therapy selection and reduce medical cost. This work focuses on developing molecular imaging companion diagnostics based on a platform we termed "target-enabled in situ ligand aggregation (TESLA)". The imaging probes, once enters disease site and activated by the target enzyme, can undergo intramolecular cyclization and self-assembly into nanoaggregates that can generate signal retention in cells. Based on this platform, we developed a new imaging probe scaffold and applied this scaffold for imaging the activity of β-galactosidase and caspases. We also developed a new caspase-sensitive positron emission tomography (PET) imaging tracer for monitoring tumor therapeutic responses to chemo and radio therapies in vivo. This PET tracer was also used in canine clinical trials and was approved by FDA for human studies. Lastly, we introduced a new pre-targeted imaging approach based on TESLA by incorporating the trans-cyclooctene (TCO)-tetrazine click chemistry into TESLA. By decoupling the imaging tag from the scaffold, the kinetics of probe activation and retention and the kinetics of imaging tag retention can be optimized independently. This method was demonstrated in imaging caspase activity in vivo using fluorescence and PET imaging
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Chen, Zixin |
|---|---|
| Degree supervisor | Rao, Jianghong |
| Thesis advisor | Rao, Jianghong |
| Thesis advisor | Kool, Eric T |
| Thesis advisor | Xia, Yan, 1980- |
| Degree committee member | Kool, Eric T |
| Degree committee member | Xia, Yan, 1980- |
| Associated with | Stanford University, Department of Chemistry. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Zixin Chen |
|---|---|
| Note | Submitted to the Department of Chemistry |
| Thesis | Thesis Ph.D. Stanford University 2020 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Zixin Chen
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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