3857-04-3Relevant articles and documents
Optimization and synthesis of an 18F-labeled dopamine D3 receptor ligand using [18F]fluorophenylazocarboxylic tert-butylester
Nebel, Natascha,Maschauer, Simone,Hocke, Carsten,Hübner, Harald,Gmeiner, Peter,Prante, Olaf
, p. 48 - 53 (2016)
There is still no efficient fluorine-18-labeled dopamine D3 subtype selective receptor ligand for studies with positron emission tomography. We aim at improving the D3 selectivity and hydrophilicity of a candidate ligand by changing the substitution pattern to a 2,3-dichlorophenylpiperazine and hydroxylation of the butyl chain. The compound [18F]3 exhibited D3 affinity of Ki = 3.6 nM, increased subtype selectivity (Ki(D2/D3) = 60), and low affinity to 5-HT1A and α1 receptors (Ki (5-HT1A/D3) = 34; Ki (α1/D3) = 100). The two-step radiosynthesis was optimized for analog [18F]4 by reducing the necessary concentration of the precursor amine (57 mM), which reacted with [18F]fluorophenylazocarboxylic tert-butylester under basic conditions. The optimization of the base (Cs 2CO3, 23 mM) and the adjustment of reaction temperature led to the radiochemical yield of 63% after 5 min at 35C. The optimized reaction conditions were transferred on to the synthesis of [18F]3 with an overall non-decay corrected yield of 8-12% in a specific activity of 32-102 GBq/μmol after a total synthesis time of 30-35 min. This provides a D 3 radioligand candidate with improved attributes concerning selectivity and radiosynthesis for further preclinical studies.
Chemoselective Radiosyntheses of Electron-Rich [18F]Fluoroarenes from Aryl(2,4,6-trimethoxyphenyl)iodonium Tosylates
Kwon, Young-Do,Son, Jeongmin,Chun, Joong-Hyun
, p. 3678 - 3686 (2019/03/11)
Hypervalent diaryliodonium salts have been used to produce various [18F]fluoroarenes. The iodonium salt approach as a labeling precursor has been established to equally afford complex 18F-fluorinated molecules. Because of the inheren
Alcohol-Enhanced Cu-Mediated Radiofluorination
Zischler, Johannes,Kolks, Niklas,Modemann, Daniel,Neumaier, Bernd,Zlatopolskiy, Boris D.
supporting information, p. 3251 - 3256 (2017/03/17)
The potential of many 18F-labeled (hetero)aromatics for applications in positron emission tomography remains underexplored because convenient procedures for their radiosynthesis are lacking. Consequently, simple methods to prepare radiofluorinated (hetero)arenes are highly sought after. Herein, we report the beneficial effect of primary and secondary alcohols on Cu-mediated 18F-labeling. This observation contradicts the assumption that such alcohols are inappropriate solvents for aromatic fluorination. Therefore, we developed a protocol for rapid radiolabeling of an extraordinarily broad scope of boronic and stannyl substrates under general reaction conditions. Notably, radiofluorinated indoles, phenols, and anilines were synthesized directly from the corresponding unprotected precursors. Furthermore, the novel method enabled the preparation of radiofluorinated tryptophans, [18F]F-DPA, [18F]DAA1106, 6-[18F]FDA, and 6-[18F]FDOPA.
