title: Whole-body distribution and radiation dosimetry of [11C]telmisartan as a biomarker for hepatic organic anion transporting polypeptide (OATP) 1B3.
abstract: BACKGROUND
  Telmisartan, a nonpeptide angiotensin II AT1 receptor antagonist used as an antihypertensive drug, is specifically taken up by the liver through the OATP1B3. PET imaging with [(11)C]telmisartan is expected to provide information about the whole body pharmacokinetics of telmisartan as well as its transport property by OATP1B3. The purpose of the study was to determine the biodistribution and radiation dosimetry of [(11)C]telmisartan in humans.
  
  
  METHODS
  Biodistribution of [(11)C]telmisartan was measured in three rats and six healthy male human volunteers. In the rat study, a dynamic emission scan was performed for 90 min. In the human study, dynamic whole-body PET images were acquired after intravenous injection of [(11)C]telmisartan. ROIs were defined for source organs on the PET images to measure time-course of [(11)C]telmisartan uptake as percentage injected dose and the number of disintegration for each organ. Radiation dosimetry was calculated with OLINDA/EXM.
  
  
  RESULTS
  In the rat study, most radioactivity was rapidly taken up by the liver and part of it was excreted into the biliary tract and intestine. Extrapolating from the rat data, the effective dose for the adult human being was estimated to be 3.65±0.01 microSv/MBq (n=3). In the human study, most of the tracer was taken up by the liver as well, although not as rapidly as in the rat. The activity in the gall bladder and intestine increased gradually. The effective dose for the adult human being was 4.24±0.09 microSv/MBq (n=6).
  
  
  CONCLUSIONS
  [(11)C]Telmisartan is a safe PET tracer with a dosimetry profile comparable to other common (11)C PET tracers.
authors.affiliation: Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima minamimachi, chuo-ku, Kobe, Hyogo, Japan. k-shimizu@kcho.jp
authors.forename: Keiji
authors.initials: K
authors.lastname: Shimizu
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Takashima
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Yamane
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sasaki
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kageyama
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Hashizume
authors.forename: Kazuya
authors.initials: K
authors.lastname: Maeda
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: D000328:Adult; D000818:Animals; D001562:Benzimidazoles / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D001565:Benzoates / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000378:metabolism; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011874:Radiometry; D051381:Rats; D012449:Safety; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D013045:Species Specificity; D000077333:Telmisartan; D055815:Young Adult
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D015415:Biomarkers; D002250:Carbon Radioisotopes; D029362:Organic Anion Transporters, Sodium-Independent; C421207:Slco1b2 protein, rat; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D000077333:Telmisartan