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

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• 作者：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)
  
• 关键词：Positron emission tomography ; Dasatinib (substance name) ; Protein ; tyrosine kinases [Mesh] ; Molecular imaging ; SKI ; 249380
• 刊名：Molecular Imaging and Biology
• 出版年：2012
• 出版时间：February 2012
• 年：2012
• 卷：14
• 期：1
• 页码：25-31
• 全文大小：358KB
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• 作者单位：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. Nuclear Medicine Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Room H-214B, Box?77, New York, NY, 10065, USA
  2. Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Room H-214B, Box?77, New York, NY, 10065, USA
  3. Radiochemistry Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box?77, Room H-214B, New York, NY, 10065, USA
  4. Sloan-Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box?77, Room H-214B, New York, NY, 10065, USA
  5. Program in Molecular Pharmacology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Room H-214B, Box?77, New York, NY, 10065, USA
  

文摘

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.