Efficient microwave-assisted direct radiosynthesis of [(18)F]PR04.MZ and [(18)F]LBT999: selective dopamine transporter ligands for quantitative molecular imaging by means of PET.
PR04.MZ 8-(4-fluoro-but-2-ynyl)-3-p-tolyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester (1) and LBT999 8-((E)-4-fluoro-but-2-enyl)-3b-p-tolyl-8-aza-bicyclo[3.2.1]octane-2beta-carboxylic acid methyl ester (2) are selective dopamine reuptake inhibitors, derived from cocaine. Compounds 1 and 2 were labelled with fluorine-18 at their terminally fluorinated N-substituents employing microwave enhanced direct nucleophilic fluorination. K[(18)F]F(-) Kryptofix 222 cryptate, tetrabutyl ammonium [(18)F]fluoride and caesium [(18)F]fluoride were compared as fluoride sources under conventional and microwave enhanced conditions. Fluorination yields were remarkably increased under microwave irradiation for all three fluoride salts. Radiochemically pure (>98%) [(18)F]PR04.MZ (0.95-1.09GBq, 42-135GBq/micromol) was obtained within 34-40min starting from 3.0GBq [(18)F]fluoride ion in 32-36% non-decay-corrected overall yield using K[(18)F]F(-)Kryptofix 222 cryptate in MeCN.
Institute of Nuclear Chemistry, Johannes Gutenberg-University, Fritz-Strassmann-Weg 2, D-55128 Mainz, Germany. pr340@wbic.cam.ac.uk
Patrick J
PJ
Riss
Frank
F
Roesch
D002586:Cesium / Q000737:chemistry; D003042:Cocaine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D005459:Fluorides / Q000737:chemistry; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling; D008024:Ligands; D008872:Microwaves; D008956:Models, Chemical; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D014326:Tropanes / Q000138:chemical synthesis / Q000737:chemistry
C508666:8-((E)-4-fluoro-but-2-enyl)-3beta-p-tolyl-8-aza-bicyclo(3.2.1)octane-2beta-carboxylic acid methyl ester; D050483:Dopamine Plasma Membrane Transport Proteins; D005462:Fluorine Radioisotopes; D008024:Ligands; C545366:PR04.MZ compound; D019275:Radiopharmaceuticals; D014326:Tropanes; D002586:Cesium; D003042:Cocaine; D005459:Fluorides; C027754:cesium fluoride