Dosimetry of 18F-labeled tyrosine kinase inhibitor SKI-249380, a dasatinib-tracer for PET imaging Journal Article
| Authors: | Dunphy, M. P. S.; Zanzonico, P.; Veach, D.; Somwar, R.; Pillarsetty, N.; Lewis, J.; Larson, S. |
| Article Title: | Dosimetry of 18F-labeled tyrosine kinase inhibitor SKI-249380, a dasatinib-tracer for PET imaging |
| 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. © Academy of Molecular Imaging and Society for Molecular Imaging, 2010. |
| Keywords: | controlled study; unclassified drug; nonhuman; radiation dose; positron emission tomography; methodology; radiopharmaceuticals; mouse; animal; mouse mutant; animals; mice; animal tissue; mus; image analysis; animal experiment; animal model; mice, scid; molecular imaging; dasatinib; pyrimidines; radiation dosage; animalia; models, animal; imaging system; chemistry; diagnostic agent; isotope labeling; nude mouse; tissue distribution; mice, nude; dosimetry; positron-emission tomography; radiopharmaceutical agent; drug tissue level; drug absorption; pyrimidine derivative; fluorine 18; thiazoles; drug excretion; fluorine radioisotopes; isoflurane; fluorine; thiazole derivative; urinary excretion; radiation absorption; large intestine; dasatinib (substance name); protein-tyrosine kinases [mesh]; ski-249380; ski 249380; biliary excretion |
| Journal Title: | Molecular Imaging and Biology |
| Volume: | 14 |
| Issue: | 1 |
| ISSN: | 1536-1632 |
| Publisher: | Springer |
| Date Published: | 2012-02-01 |
| Start Page: | 25 |
| End Page: | 31 |
| Language: | English |
| DOI: | 10.1007/s11307-010-0462-2 |
| PROVIDER: | scopus |
| PMCID: | PMC3113455 |
| PUBMED: | 21161687 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 July 2012" - "CODEN: CPIMF" - "Source: Scopus" |
Altmetric
Citation Impact
Related MSK Work