Total synthesis and evaluation of [18F]MHMZ.
Radiochemical labeling of MDL 105725 using the secondary labeling precursor 2-[(18)F]fluoroethyltosylate ([(18)F]FETos) was carried out in yields of approximately 90% synthesizing [(18)F]MHMZ in a specific activity of approximately 50MBq/nmol with a starting activity of approximately 3GBq. Overall radiochemical yield including [(18)F]FETos synthon synthesis, [(18)F]fluoroalkylation and preparing the injectable [(18)F]MHMZ solution was 42% within a synthesis time of approximately 100 min. The novel compound showed excellent specific binding to the 5-HT(2A) receptor (K(i)=9.0 nM) in vitro and promising in vivo characteristics.
Herth
Matthias M
MM
Institute of Nuclear Chemistry, University of Mainz, Fritz-Strassmann-Weg 2, 55128 Mainz, Germany.
Debus
Fabian
F
Piel
Markus
M
Palner
Mikael
M
Knudsen
Gitte M
GM
Lüddens
Hartmut
H
Rösch
Frank
F
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D005464:Fluorobenzenes / Q000138:chemical synthesis* / Q000737:chemistry; D007553:Isotope Labeling; D007650:Ketanserin / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D007700:Kinetics; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D011869:Radioligand Assay; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics
C528727:2-(18F)fluoro-ethoxy-3-methoxyphenyl)-1-(2-(4-fluoro-phenyl)ethyl-4-piperidine-methanol; D005462:Fluorine Radioisotopes; D005464:Fluorobenzenes; D010880:Piperidines; D019275:Radiopharmaceuticals; D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; C071983:altanserin; D007650:Ketanserin; C079049:volinanserin