Human Dosimetry of Carbon-11 Labeled N-butan-2-yl-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide Extrapolated from Whole-body Distribution Kinetics and Radiometabolism in Rats

: Luoto P, Laitinen I, Suilamo S, Nagren K, Roivainen A

Publisher: SPRINGER

: 2010

: Molecular Imaging and Biology

: MOLECULAR IMAGING AND BIOLOGY

: MOL IMAGING BIOL

: 4

: 12

: 4

: 435

: 442

: 8

: 1536-1632

DOI: https://doi.org/10.1007/s11307-009-0293-1

Results: PET imaging of rats showed the highest radioactivity levels in heart, kidneys, thyroid gland, liver, and lungs. The radioactivity cleared rapidly from lungs and slowly from heart and liver. However, much of the radioactivity retained in kidneys, which was in concordance with the observed low urinary excretion of [(11)C]PK11195. Extrapolating from the rat data, the effective dose of [(11)C]PK11195 for a 70-kg man was estimated to be 4.2 +/- 0.3 mu Sv/MBq. Five different radiometabolites were detected in rat plasma, and the level of intact [(11)C]PK11195 decreased from 80% +/- 11% (mean +/- SD) at 10 min to 44% +/- 5% at 40 min after injection. In rat heart, brain, kidney, and lung homogenates, more than 90% of total radioactivity originated from intact [(11)C]PK11195. In liver, however, the amount of [(11)C]PK11195 was approximately 70% and decreased over time, indicating metabolism by liver enzymes.