Plasma pharmacokinetics, whole-body distribution, metabolism, and radiation dosimetry of 68Ga bombesin antagonist BAY 86-7548 in healthy men

J Nucl Med. 2013 Jun;54(6):867-72. doi: 10.2967/jnumed.112.114082. Epub 2013 Apr 5.

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.

Conclusion: 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.

Keywords: 68Ga; PET; dosimetry; pharmacokinetics; radiometabolism; whole-body distribution.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bombesin / antagonists & inhibitors*
  • Health*
  • Humans
  • Male
  • Middle Aged
  • Oligopeptides / adverse effects
  • Oligopeptides / pharmacokinetics*
  • Oligopeptides / pharmacology*
  • Radiochemistry
  • Radiometry
  • Safety
  • Tissue Distribution

Substances

  • BAY 86-7548
  • Oligopeptides
  • Bombesin