A1 Refereed original research article in a scientific journal
Plasma Pharmacokinetics, Whole-Body Distribution, Metabolism, and Radiation Dosimetry of Ga-68 Bombesin Antagonist BAY 86-7548 in Healthy Men
Authors: Roivainen A, Kahkonen E, Luoto P, Borkowski S, Hofmann B, Jambor I, Lehtio K, Rantala T, Rottmann A, Sipila H, Sparks R, Suilamo S, Tolvanen T, Valencia R, Minn H
Publisher: SOC NUCLEAR MEDICINE INC
Publication year: 2013
Journal: Journal of Nuclear Medicine
Journal name in source: JOURNAL OF NUCLEAR MEDICINE
Journal acronym: J NUCL MED
Number in series: 6
Volume: 54
Issue: 6
First page : 867
Last page: 872
Number of pages: 6
ISSN: 0161-5505
DOI: https://doi.org/10.2967/jnumed.112.114082
Abstract
This first-in-human study investigated the safety, tolerability, metabolism, pharmacokinetics, biodistribution, and radiation dosimetry of Ga-68-bombesin antagonist Ga-68-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.
This first-in-human study investigated the safety, tolerability, metabolism, pharmacokinetics, biodistribution, and radiation dosimetry of Ga-68-bombesin antagonist Ga-68-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.
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