Abstract
Purpose
To obtain estimates of human normal-organ radiation doses of 18F-SKI-249380, as a prerequisite step towards first-in-human trial. 18F-SKI-249380 is a first-of-its-kind PET tracer for imaging the in vivo pharmacokinetics of dasatinib, an investigational targeted therapy for solid malignancies.
Procedures
Isoflurane-anesthetized mice received tracer dose via tail vein. Organ time-integrated activity coefficients, fractional urinary and hepatobiliary excretion, and total-body clearance kinetics were derived from PET data, with allometric extrapolation to the Standard Man anatomic model and normal-organ-absorbed dose calculations using OLINDA/EXM software.
Results
The human effective dose was 0.031 mSv/MBq. The critical organ was the upper large intestine, with a dose equivalent of 0.25 mSv/MBq. A 190-MBq administered activity of 18F-SKI-249380 is thus predicted to expose an adult human to radiation doses generally comparable to those of routinely used diagnostic radiopharmaceuticals.
Conclusions
Animal-based human dose estimates support first-in-human testing of 18F-SKI-249380.
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Acknowledgments
This research was funded by the National Cancer Institute through a Molecular Imaging Training for Oncology Program grant (R25-CA96945) and an In Vivo Cellular and Molecular Imaging Center (ICMIC) grant (P50-CA086438). Technical services provided by the MSKCC Small-Animal Imaging Core Facility were supported in part by an NIH Small-Animal Imaging Research Program (SAIRP) grant (R24 CA83084) and an NIH Center grant (P30 CA08748). The authors gratefully acknowledge the contributions of the MSKCC Radiochemistry/Cyclotron Core Facility; technical assistance by Manda Null, Lars Stelter, and Daniel Shin;discussions with Drs. Elmer Santos, Michelle Bradbury and Oula Penate-Medina; and feedback provided two anonymous reviewers, which significantly improved the quality of this manuscript.
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The authors declare they have no conflicts of interest.
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Dunphy, M.P.S., Zanzonico, P., Veach, D. et al. Dosimetry of 18F-Labeled Tyrosine Kinase Inhibitor SKI-249380, a Dasatinib-Tracer for PET Imaging. Mol Imaging Biol 14, 25–31 (2012). https://doi.org/10.1007/s11307-010-0462-2
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DOI: https://doi.org/10.1007/s11307-010-0462-2