title: The clinical safety, biodistribution and internal radiation dosimetry of flutemetamol (¹⁸F) injection in healthy Japanese adult volunteers.
abstract: OBJECTIVE
  The Phase I safety, biodistribution and internal radiation dosimetry study in adult healthy Japanese males of flutemetamol ((18)F) injection, an in vivo β-amyloid imaging agent, is reported and compared with previously obtained Caucasian data.
  
  
  METHODS
  Whole-body PET scans of 6 healthy volunteers (age 51.8-61.7 years) were acquired approximately 4 h post-injection (administered activity 102-160 MBq). Venous blood sampling determined (18)F activity concentrations in whole blood and plasma and high-performance liquid chromatography (HPLC) established the percentages of parent [(18)F]flutemetamol and its metabolites. Voided urine activity was recorded. The decay-corrected and normalised (18)F activity of 14 source organ regions as a function of time was entered into the OLINDA/EXM software to calculate the internal radiation dosimetry and effective dose of each subject following the MIRD schema. The pharmacokinetics, biodistribution and dosimetry profiles were compared to data obtained from a cohort of healthy Caucasian adult volunteers from a previous Phase I study of [(18)F]flutemetamol.
  
  
  RESULTS
  Flutemetamol ((18)F) injection was well tolerated. The highest mean initial uptakes were measured in the liver (15.2%), lungs (10.2%) and brain (6.6%). The highest mean radiation absorbed doses were received by the gallbladder wall (366 μGy/MBq), upper large intestine (138 μGy/MBq) and small intestine (121 μGy/MBq). The mean effective dose was 34.9 μSv/MBq. HPLC analysis demonstrated that at 5-min post-injection about 75% of plasma (18)F radioactivity was in the form of parent [(18)F]flutemetamol, reducing to 8 and 2% at 25 and 90 min, respectively, giving rise to less lipophilic (18)F-labelled metabolites. Comparisons with the Caucasian cohort showed no differences that could be regarded as clinically significant.
  
  
  CONCLUSIONS
  The clinical safety of [(18)F]flutemetamol demonstrated no differences of clinical significance in the pharmacokinetics, biodistribution and internal radiation dosimetry profiles between Caucasian and Japanese adults.
authors.affiliation: Division of Molecular Imaging, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Senda
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: Gill
authors.initials: G
authors.lastname: Farrar
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Somer
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Paterson
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sasaki
authors.forename: Brian J
authors.initials: BJ
authors.lastname: McParland
mesh_terms: D000814:Aniline Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D044466:Asian People; D052160:Benzothiazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000009:adverse effects* / Q000379:methods*; D011829:Radiation Dosage; D011874:Radiometry; D012449:Safety; D014018:Tissue Distribution
chemical_list: D000814:Aniline Compounds; D052160:Benzothiazoles; C581552:flutemetamol