title: A multi species evaluation of the radiation dosimetry of [11C]erlotinib, the radiolabeled analog of a clinically utilized tyrosine kinase inhibitor.
abstract: BACKGROUND
  Erlotinib is a tyrosine kinase inhibitor prescribed for non-small cell lung cancer (NSCLC) patients bearing epidermal growth factor receptor mutations in the kinase domain. The objectives of this study were to (1) establish a human dosimetry profile of [11C]erlotinib and (2) assess the consistency of calculated equivalent dose across species using the same dosimetry model.
  
  
  METHODS
  Subjects examined in this multi-species study included: a stage IIIa NSCLC patient, 3 rhesus macaque monkeys, a landrace pig, and 4 athymic nude-Fox1nu mice. [11C]erlotinib PET data of the whole body were acquired dynamically for up to 120min. Regions of interest (ROIs) were manually drawn to extract PET time activity curves (TACs) from identifiable organs. TACs were used to calculate time-integrated activity coefficients (residence times) in each ROI, which were then used to calculate the equivalent dose in OLINDA. Subject data were used to predict the equivalent dose to the organs of a 73.7kg human male.
  
  
  RESULTS
  In three of four species, the liver was identified as the organ receiving the highest equivalent dose (critical organ). The mean equivalent doses per unit of injected activity to the liver based on human, monkey, and mouse data were 29.4μSv/MBq, 17.4±6.0μSv/MBq, and 5.27±0.25μSv/MBq, respectively. The critical organ based on the pig data was the gallbladder wall (20.4μSv/MBq) but the liver received a nearly identical equivalent dose (19.5μSv/MBq).
  
  
  CONCLUSIONS
  (1) When designing PET studies using [11C]erlotinib, the liver should be considered the critical organ. (2) In organs receiving the greatest equivalent dose, mouse data underestimated the dose in comparison to larger species. However, the effective dose of [11C]erlotinib to the whole body of a 73.7kg man was predicted with good consistency based on mice (3.14±0.05μSv/MBq) or the larger species (3.46±0.25μSv/MBq).
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, United States; Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States.
authors.forename: J Ryan
authors.initials: JR
authors.lastname: Petrulli
authors.affiliation: Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Søren B
authors.initials: SB
authors.lastname: Hansen
authors.affiliation: Hadassah Cyclotron Unit, Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Galith
authors.initials: G
authors.lastname: Abourbeh
authors.affiliation: Department of Radiology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Maqsood
authors.initials: M
authors.lastname: Yaqub
authors.affiliation: Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Idris
authors.initials: I
authors.lastname: Bahce
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Holden
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States.
authors.forename: Nabeel B
authors.initials: NB
authors.lastname: Nabulsi
authors.affiliation: Department of Therapeutic Radiology, Yale University, New Haven, CT, United States.
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Contessa
authors.affiliation: Hadassah Nuclear Medicine Institute, Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Mishani
authors.affiliation: Department of Nuclear Medicine and PET Research, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, United States; Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States. Electronic address: evan.morris@yale.edu.
authors.forename: Evan D
authors.initials: ED
authors.lastname: Morris
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging; D000069347:Erlotinib Hydrochloride / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D007553:Isotope Labeling; D008175:Lung Neoplasms / Q000000981:diagnostic imaging; D008253:Macaca mulatta; D051379:Mice; D000072078:Positron Emission Tomography Computed Tomography; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011874:Radiometry; D013552:Swine; D014018:Tissue Distribution
chemical_list: D047428:Protein Kinase Inhibitors; D000069347:Erlotinib Hydrochloride; D011505:Protein-Tyrosine Kinases
keywords: Dosimetry; Erlotinib; OLINDA; Radiation; TKI