Fluorescent probes are useful tools for studying chemical biology, available in a wide variety of colours and applicable to different biochemical processes. One of their hallmarks is the ability to tune their chemistry and allow them to selectively “turn on” in response to different biomolecular targets of interest. However, fluorescence is largely limited by shallow tissue depth of penetration. Magnetic resonance imaging (MRI) can overcome the depth of penetration limitations to better map these biochemical processes and mechanisms with contrast agents. Chemical exchange saturation transfer (CEST) MRI is an alternative method to generating contrast in MR imaging that, like fluorescence, can provide multiplexed imaging by varying the chemical shift of the exchangeable proton on the contrast agent. Previously, a paramagnetic CEST agent containing two tetramethylpiperidinyloxyl (TEMPO) moieties was shown to reduce the CEST signal of a lanthanide complex due to T1 shortening effects on bulk water. Herein, we present a probe design strategy capable of suppressing the diamagnetic CEST (diaCEST) signal with the use of an N-hydroxy piperidine moiety. This discovery that N-hydroxy piperidine is capable of suppressing the diaCEST signal was applied to the study the activity of fibroblast activation protein-α (FAP). FAP is an enzyme involved in maintaining the tumour environment and its interactions can help understand tumour development, invasion and metastasis.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/41091 |
| Date | 24 September 2020 |
| Creators | Truong, Yen Janette |
| Contributors | Shuhendler, Adam Jason |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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