Molecular Imaging and Biology

, Volume 14, Issue 1, pp 25–31

Dosimetry of 18F-Labeled Tyrosine Kinase Inhibitor SKI-249380, a Dasatinib-Tracer for PET Imaging

  • Mark P. S. Dunphy
  • Pat Zanzonico
  • Darren Veach
  • Romel Somwar
  • Nagavarakishore Pillarsetty
  • Jason Lewis
  • Steven Larson
Brief Article

DOI: 10.1007/s11307-010-0462-2

Cite this article as:
Dunphy, M.P.S., Zanzonico, P., Veach, D. et al. Mol Imaging Biol (2012) 14: 25. doi:10.1007/s11307-010-0462-2

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.

Key words

Positron emission tomography Dasatinib (substance name) Protein-tyrosine kinases [Mesh] Molecular imaging SKI-249380 

Supplementary material

11307_2010_462_MOESM1_ESM.pdf (18 kb)
ESM 1(PDF 17 kb)
11307_2010_462_MOESM2_ESM.pdf (111 kb)
ESM 2(PDF 111 kb)
11307_2010_462_MOESM3_ESM.pdf (75 kb)
ESM 3(PDF 74 kb)

Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2010

Authors and Affiliations

  • Mark P. S. Dunphy
    • 1
  • Pat Zanzonico
    • 2
  • Darren Veach
    • 3
  • Romel Somwar
    • 4
  • Nagavarakishore Pillarsetty
    • 3
  • Jason Lewis
    • 3
    • 5
  • Steven Larson
    • 1
    • 5
  1. 1.Nuclear Medicine ServiceMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Department of Medical PhysicsMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Radiochemistry ServiceMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  4. 4.Sloan-Kettering Institute for Cancer ResearchMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  5. 5.Program in Molecular PharmacologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA

Personalised recommendations