Synthesis of fluorine-18 labelled radiotracers and their pre-clinical and clinical characterization
Metadata
Show metadataAppears in the following Collection
- Kjemisk institutt [1539]
Abstract
Positron emission tomography (PET) is one of the most sensitive in vivo imaging techniques available to clinicians and researchers. It helps in understanding the biological interactions and mechanism of various diseases through use of radiolabelled compounds called radiotracers. Herein is described the development of facile radiolabelling approaches for straightforward access to 18F-labelled trifluoromethyl radiotracers. Direct nucleophilic radiofluorination of difluorovinyl precursors was achieved for 18F-trifluoromethylation of aliphatic compounds, and applied to the radiosynthesis of [18F]lansoprazole and N-methyl[18F]lansoprazole. The compounds were used to analyze the blood-brain barrier penetration in healthy persons and for the detection of tau-neurofibrillary tangles in Alzheimer’s patients. For 18F-trifluoromethylation of aromatic compounds, in situ synthesis of Cu[18F]CF3 was achieved and used in 18F-trifluoromethylation of iodo-arenes using a single vial one-step method. The procedure was applied for radiosynthesis of a derivative of AH7921, which is a sub-type selective mu-opioid receptor agonist. The developed procedures are applicable to available radiosynthesis hardware, and provide access to desired compounds within 40 minutes in high radiochemical yields. In addition, a series of new compounds were synthesized with aim to discover the new radioligands based on modifications to the lead compounds i.e. lansoprazole and AH7921. Several interesting candidates with good combination of affinity and selectivity were identified from each series, and radiolabelled with fluorine-18. The newly developed 18F-labelled compounds have good potential to provide the in vivo characterization of tau-neurofibrillary tangles and quantification of the opioid receptors using the PET imaging.List of papers
Paper I: Direct nucleophilic radiosynthesis of [18F]trifluoroethyl tosylate. Riss PJ, Rafique W, Aigbirhio FI. In: Scott PJ. Radiochemical Syntheses: Further Radiopharmaceuticals for Positron Emission Tomography and New Strategies for Their Production, Volume 2. Hoboken, New Jersey: John Wiley & Sons; 2015. Print ISBN: 9781118237847. Online ISBN: 9781118834114 The chapter is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1002/9781118834114 |
Paper II: Image guided development of heterocyclic sulfoxides as ligands for tau neurofibrillary tangles: From first-in-man to second generation ligands. Rafique W, Kramer V, Pardo T, Smits R, Spilhaug MM, Hoepping A, Savio E, Engler H, Kuljs R, Amaral H, Riss PJ. ACS Omega. 2018;3(7):7567-79. The article is included in the thesis. Also available at: https://doi.org/10.1021/acsomega.8b00975 |
Paper III: Cu(I)-mediated 18F-trifluoromethylation of arenes: Rapid synthesis of 18F-labeled trifluoromethyl arenes. Rühl T, Rafique W, Lien VT, Riss PJ. Chem Comm. 2014;50(45):6056-59. The article is included in the thesis. Also available at: https://doi.org/10.1039/c4cc01641f |
Paper IV: Reaching out for Sensitive Evaluation of the Mu Opioid Receptor in vivo: Positron Emission Tomography Imaging of the Agonist [11C]AH7921. Rafique W, Khanapur S, Spilhaug MM, Riss PJ. ACS chem neurosci. 2017; 8(9): 1847-52. The article is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1021/acschemneuro.7b00075 |
Paper V: Fully automated radiosynthesis of three mu-selective opioid receptor agonists for in vivo imaging with Positron Emission Tomography (manuscript). Rafique W, Riss PJ. To be published. The paper is not available in DUO awaiting publishing. |
Paper VI: Discovery of an 18F-labelled selective μ-opioid receptor agonist for small animal PET: Radiosynthesis, in-vitro and in-vivo characterisation of 3-chloro-4-[18F]fluoro-N-(1-(dimethylamino)cyclohexyl)methyl benzamide (manuscript). Ott J, Rafique W, Maschauer S, Hartvig K, Spilhaug MM, Jakobsson JE, Hübner H, Gmeiner P, Prante O, Riss PJ. To be published. The paper is not available in DUO awaiting publishing. |
Paper VII: Radiosynthesis and characterization of 3-trifluoromethyl-4-[18F]fluoro-N-(1-(dimethylamino)cyclohexyl)methyl benzamide as an 18F-labelled mu-selective opioid receptor agonist. (manuscript). Rafique W, Ott JJ, Maschauer S, Hartvig K, Jakobsson JE, Spilhaug MM, Hübner H, Gmeiner P, Prante O, Riss PJ. To be published. The paper is not available in DUO awaiting publishing. |