title: First automatic radiosynthesis of 11C labeled Telmisartan using a multipurpose synthesizer for clinical research use.
abstract: OBJECTIVE
  Telmisartan, a nonpeptide angiotensin II AT1 receptor antagonist, is an antihypertensive drug. Positron emission tomography (PET) imaging with [(11)C]Telmisartan is expected to provide information about the whole body pharmacokinetics of telmisartan as well as the transport function of hepatic OATP1B3. We developed a first automatic preparation system of [(11)C]Telmisartan to applicable clinical research using a new (11)C and (18)F multipurpose synthesizer.
  
  
  METHODS
  Two milligrams of precursor (1) in 5 μl of 1 M KOH in 0.5 ml of dimethyl sulfoxide was reacted with [(11)C]CH(3)I for 5 min at 120°C. The resultant solution was hydrolyzed with 1 M NaOH at 100°C for 3 min. The neutralization was carried out with acetic acid, followed by purification with high-performance liquid chromatography. The desired radioactive fraction was collected and solvent was replaced by 10 ml saline containing 0.3 ml of EtOH and 0.5 ml of PEG400, and then passed through a sterile 0.22 μm filter (Millex-GV, Millipore) to a pyrogen-free vial as the final product.
  
  
  RESULTS
  The yield of [(11)C]Telmisartan for clinical research use was 16.8 ± 2.9% EOB as decay corrected (n = 8, mean ± SD) in 32-36 min. The radiochemical purity of [(11)C]Telmisartan was >97%, and specific activity was higher than 86.3 MBq/nmol.
  
  
  CONCLUSIONS
  We succeeded in the first synthesis of [(11)C]Telmisartan for clinical research use by appropriate quality tests.
authors.affiliation: Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Iimori
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Hashizume
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sasaki
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kajiwara
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Michio
authors.initials: M
authors.lastname: Senda
mesh_terms: D001331:Automation; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000592:standards; D001565:Benzoates / Q000138:chemical synthesis* / Q000737:chemistry / Q000592:standards; D035843:Biomedical Research / Q000295:instrumentation / Q000379:methods* / Q000592:standards; D002250:Carbon Radioisotopes; D049268:Positron-Emission Tomography; D011786:Quality Control; D011854:Radiochemistry / Q000295:instrumentation / Q000379:methods* / Q000592:standards; D000077333:Telmisartan
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D002250:Carbon Radioisotopes; D000077333:Telmisartan