title: Dosimetry of 18F-labeled tyrosine kinase inhibitor SKI-249380, a dasatinib-tracer for PET imaging.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Nuclear Medicine Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Room H-214B, Box 77, New York, NY 10065, USA. dunphym@mskcc.org
authors.forename: Mark P S
authors.initials: MP
authors.lastname: Dunphy
authors.forename: Pat
authors.initials: P
authors.lastname: Zanzonico
authors.forename: Darren
authors.initials: D
authors.lastname: Veach
authors.forename: Romel
authors.initials: R
authors.lastname: Somwar
authors.forename: Nagavarakishore
authors.initials: N
authors.lastname: Pillarsetty
authors.forename: Jason
authors.initials: J
authors.lastname: Lewis
authors.forename: Steven
authors.initials: S
authors.lastname: Larson
mesh_terms: D000818:Animals; D000069439:Dasatinib; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D023421:Models, Animal; D057054:Molecular Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D011743:Pyrimidines / Q000737:chemistry / Q000493:pharmacokinetics*; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics*; D013844:Thiazoles / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D013844:Thiazoles; D000069439:Dasatinib