Plasma Pharmacokinetics, Whole-Body Distribution, Metabolism, and Radiation Dosimetry of Ga-68 Bombesin Antagonist BAY 86-7548 in Healthy Men

: 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

: 2013

: Journal of Nuclear Medicine

: JOURNAL OF NUCLEAR MEDICINE

: J NUCL MED

: 6

: 54

: 6

: 867

: 872

: 6

: 0161-5505

DOI: https://doi.org/10.2967/jnumed.112.114082

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.