Loading...
Please wait, while we are loading the content...
Similar Documents
Développement et radiosynthèse de ligands du récepteur tyrosine kinase neurotrophique type 2 (TrkB) marqués aux carbone-11 et fluor-18 pour l’imagerie cérébrale par tomographie d’émission de positons
| Content Provider | Semantic Scholar |
|---|---|
| Author | Bernard-Gauthier, Vadim |
| Copyright Year | 2014 |
| Abstract | This thesis describes my contribution leading to the development of the firstgeneration positron emission tomography (PET) radioligands labeled with fluorine-18 (t1/2 = 110 min) or carbon-11 (t1/2 = 20.4 min) for the in vivo brain imaging of tropomyosin-related kinase B (TrkB). This research follows from the recent discovery of non-peptidic, high-affinity TrkB ligands derived from 7,8-dihydroxyflavone. The synthesis of non-radioactive 7,8-dihydroxyflavone derivatives and radiolabeling precursors amenable to fluorine-18 and carbon-11 incorporation was performed. Two synthesized compounds have been brought forward as precursors for radiolabeling with either fluorine-18 or carbon-11. Radiosynthesis involved either a novel nucleophilic aromatic subsitution with [ 18 F]fluoride, or N-methylation with [ 11 C]methyl iodide or [ 11 C] methyl triflate. The resulting radiotracers were assessed in vitro by autoradiography and in vivo by PET scans of rats. The physicochemical properties and serum stability of these tracers were also evaluated. X-ray crystal structures of a series of synthetic flavone analogues were used as basis for structure-activity relationship (SAR) analysis. In combination with the above in vivo PET evaluation of these compounds, certain pharmacophores were shown essential for ligand binding affinity. In addition, some structural fragments were associated with in vivo ligand metabolism. The development and radiosynthesis of a third TrkB radiotracer, along with its in vivo PET evaluation and structural analysis, is also described here. In all, better understanding of these tracers have led to the design of potential second-generation TrkB ligands with more optimal properties as PET radiotracers. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://papyrus.bib.umontreal.ca/xmlui/bitstream/handle/1866/10664/Vadim_Bernard-Gauthier_Memoire_2013.pdf?isAllowed=y&sequence=2 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
