title: Plasma pharmacokinetics, whole-body distribution, metabolism, and radiation dosimetry of 68Ga bombesin antagonist BAY 86-7548 in healthy men.
abstract: This first-in-human study investigated the safety, tolerability, metabolism, pharmacokinetics, biodistribution, and radiation dosimetry of (68)Ga-bombesin antagonist (68)Ga-DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (BAY 86-7548).
  
  
  METHODS
  Five healthy men underwent dynamic whole-body PET/CT after an intravenous injection of BAY 86-7548 (138 ± 5 MBq). Besides total radioactivity, plasma samples were analyzed by radio-high-performance liquid chromatography for metabolism of the tracer. Dosimetry was calculated using the OLINDA/EXM software.
  
  
  RESULTS
  Three radioactive plasma metabolites were detected. The proportion of unchanged BAY 86-7548 decreased from 92% ± 9% at 1 min after injection to 19% ± 2% at 65 min. The organs with the highest absorbed doses were the urinary bladder wall (0.62 mSv/MBq) and the pancreas (0.51 mSv/MBq). The mean effective dose was 0.051 mSv/MBq. BAY 86-7548 was well tolerated by all subjects.
  
  
  CONCLUSIONS
  Intravenously injected BAY 86-7548 is safe, and rapid metabolism is demonstrated. A 150-MBq injection of BAY 86-7548 results in an effective dose of 7.7 mSv, which could be reduced to 5.7 mSv with frequent bladder voids.
authors.affiliation: Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland. anne.roivainen@utu.fi
authors.forename: Anne
authors.initials: A
authors.lastname: Roivainen
authors.forename: Esa
authors.initials: E
authors.lastname: Kähkönen
authors.forename: Pauliina
authors.initials: P
authors.lastname: Luoto
authors.forename: Sandra
authors.initials: S
authors.lastname: Borkowski
authors.forename: Birte
authors.initials: B
authors.lastname: Hofmann
authors.forename: Ivan
authors.initials: I
authors.lastname: Jambor
authors.forename: Kaisa
authors.initials: K
authors.lastname: Lehtiö
authors.forename: Tuija
authors.initials: T
authors.lastname: Rantala
authors.forename: Antje
authors.initials: A
authors.lastname: Rottmann
authors.forename: Henri
authors.initials: H
authors.lastname: Sipilä
authors.forename: Rick
authors.initials: R
authors.lastname: Sparks
authors.forename: Sami
authors.initials: S
authors.lastname: Suilamo
authors.forename: Tuula
authors.initials: T
authors.lastname: Tolvanen
authors.forename: Ray
authors.initials: R
authors.lastname: Valencia
authors.forename: Heikki
authors.initials: H
authors.lastname: Minn
mesh_terms: D001839:Bombesin / Q000037:antagonists & inhibitors*; D006262:Health; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011854:Radiochemistry; D011874:Radiometry; D012449:Safety; D014018:Tissue Distribution
chemical_list: C582579:BAY 86-7548; D009842:Oligopeptides; D001839:Bombesin
keywords: 68Ga; PET; dosimetry; pharmacokinetics; radiometabolism; whole-body distribution