title: Radiosynthesis and radiopharmacological evaluation of [N-methyl-11C]Org 34850 as a glucocorticoid receptor (GR)-binding radiotracer.
abstract: The radiosynthesis of [N-methyl-(11)C]Org 34850 as a potential brain glucocorticoid receptor (GR)-binding radiotracer is described. The radiosynthesis was accomplished via N-methylation of the corresponding desmethyl precursor with [(11)C]methyl triflate in a remotely controlled synthesis module to give the desired compound in a radiochemical yield of 23+/-5% (decay-corrected, based upon [(11)C]CO(2)) at a specific activity of 47+/-12 GBq/micromol (n=15) at the end-of-synthesis (EOS). The radiochemical purity after semi-preparative HPLC purification exceeded 95%. The total synthesis time was 35-40 min after end-of-bombardment (EOB). The radiotracer is rapidly metabolized in rat plasma leading to the formation of two more hydrophilic metabolites as the major metabolites. Radiopharmacological evaluation involving biodistribution and small animal PET imaging in normal Wistar rats showed that the compound [N-methyl-(11)C]Org 34850 is not able to sufficiently penetrate the blood-brain barrier. Therefore, compound [N-methyl-(11)C]Org 34850 seems not to be a suitable PET radiotracer for imaging rat brain GRs. However, involvement of Pgp or species differences requires further clarification to establish whether the radiotracer [N-methyl-(11)C]Org 34850 may still represent a suitable candidate for imaging GRs in humans.
authors.affiliation: Institut für Radiopharmazie, Forschungszentrum Dresden-Rossendorf e.V., POB 51 01 19, D-01314 Dresden, Germany. frankwue@cancerboard.ab.ca
authors.forename: Frank
authors.initials: F
authors.lastname: Wuest
authors.forename: Torsten
authors.initials: T
authors.lastname: Kniess
authors.forename: Brian
authors.initials: B
authors.lastname: Henry
authors.forename: Bernardus W M M
authors.initials: BW
authors.lastname: Peeters
authors.forename: Peter H G
authors.initials: PH
authors.lastname: Wiegerinck
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
authors.forename: Ralf
authors.initials: R
authors.lastname: Bergmann
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D002250:Carbon Radioisotopes; D006801:Humans; D008745:Methylation; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013256:Steroids / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D013450:Sulfones / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D002250:Carbon Radioisotopes; C526063:Org 34850; D019275:Radiopharmaceuticals; D011965:Receptors, Glucocorticoid; D013256:Steroids; D013450:Sulfones