139058-97-2Relevant academic research and scientific papers
Synthesis and imaging validation of [18F]MDL100907 enabled by Ni-mediated fluorination
Ren, Hong,Wey, Hsiao-Ying,Strebl, Martin,Neelamegam, Ramesh,Ritter, Tobias,Hooker, Jacob M.
, p. 611 - 615 (2014)
Several voids exist in reliable positron emission tomography (PET) radioligands for quantification of the serotonin (5HT) receptor system. Even in cases where 5HT radiotracers exist, challenges remain that have limited the utility of 5HT imaging in clinical research. Herein we address an unmet need in 5HT2a imaging using innovative chemistry. We report a scalable and robust synthesis of [18F]MDL100907, which was enabled by a Ni-mediated oxidative fluorination using [18F]fluoride. This first demonstration of a Ni-mediated fluorination used for PET imaging required development of a new reaction strategy that ultimately provided high specific activity [18F]MDL100907. Using the new synthetic strategy and optimized procedure, [18F]MDL100907 was evaluated against [ 11C]MDL100907 for reliability to quantify 5HT2a in the nonhuman primate brain and was found to be superior based on a single scan analysis using the same nonhuman primate. The use of this new 5HT2a radiotracer will afford clinical neuroscience research the ability to distinguish 5HT2a receptor abnormalities binding between healthy subjects and patients even when group differences are small.
Synthesis, radiofluorination and first evaluation of (±)-[ 18F]MDL 100907 as serotonin 5-HT2A receptor antagonist for PET
Muehlhausen, Ute,Ermert, Johannes,Herth, Matthias M.,Coenen, Heinz H.
experimental part, p. 6 - 12 (2009/04/18)
In some psychiatric disorders 5-HT2A receptors play an important role. In order to investigate those in vivo there is an increasing interest in obtaining a metabolically stable, subtype selective and high affinity radioligand for receptor binding studies using positron emission tomography (PET). Combining the excellent in vivo properties of [11C]MDL 100907 for PET imaging of 5-HT2A receptors and the more suitable half-life of fluorine-18, MDL 100907 was radiofluorinated in four steps using 1-(2-bromoethyl)-4-[18F]fluorobenzene as a secondary labelling precursor. The complex reaction required an overall reaction time of 140 min and (±)-[18F]MDL 100907 was obtained with a specific activity of at least 30 GBq/μmol (EOS) and an overall radiochemical yield of 1-2%. In order to verify its binding to 5-HT2A receptors, in vitro rat brain autoradiography was conducted showing the typical distribution of 5-HT 2A receptors and a very low non-specific binding of about 6% in frontal cortex, using ketanserin or spiperone for blocking. Thus, [18F]MDL 100907 appears to be a promising new 5-HT2A PET ligand. Copyright
