title: Radiation dose estimates for [18F]5-fluorouracil derived from PET-based and tissue-based methods in rats.
abstract: BACKGROUND
  Radiation dosimetry assessment often begins with measuring pharmaceutical biodistribution in rodents. The traditional approach to dosimetry in rodents involves a radioassay ex vivo of harvested organs at different time points following administration of the radiopharmaceutical. The emergence of small-animal positron emission tomography (PET) presents the opportunity for an alternative method for making radiodosimetry estimates previously employed only in humans and large animals. In the current manuscript, normal-tissue absorbed dose estimates for the 18F-labeled chemotherapy agent [18F]5-fluorouracil ([18F]5-FU) were derived by PET imaging- and by tissue harvesting-based methods in rats.
  
  
  METHODS
  Small-animal PET data were acquired dynamically for up to 2 h after injection of [18F]5-FU in anesthetized rats (n=16). Combined polynomial and exponential functions were used to model the harvesting-based and imaging-based time-activity data. The measured time-activity data were extrapolated to modeled (i.e., Standard Man) human organs and human absorbed doses calculated.
  
  
  RESULTS
  Organ activities derived by imaging-based and by harvesting-based methods were highly correlated (r>0.999) as were the projected human dosimetry estimates across organs (r=0.998) obtained with each method. The tissues calculated to receive highest radiation dose by both methods were related to routes of excretion (bladder wall, liver, and intestines). The harvesting-based and imaging-based methods yielded effective dose (ED) of 2.94E-2 and 2.97E-2 mSv/MBq, respectively.
  
  
  CONCLUSIONS
  Small-animal PET presents an opportunity for providing radiation dose estimates with statistical and logistical advantages over traditional tissue harvesting-based methods.
authors.affiliation: Molecular and Medical Pharmacology, Ahmanson Biological Imaging Division, UCLA Medical Center, Los Angeles, CA 90095-6942, USA.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Kesner
authors.forename: Wei-Ann
authors.initials: WA
authors.lastname: Hsueh
authors.forename: Johannes
authors.initials: J
authors.lastname: Czernin
authors.forename: Henry
authors.initials: H
authors.lastname: Padgett
authors.forename: Michael E
authors.initials: ME
authors.lastname: Phelps
authors.forename: Daniel H S
authors.initials: DH
authors.lastname: Silverman
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D005472:Fluorouracil / Q000493:pharmacokinetics; D006801:Humans; D049268:Positron-Emission Tomography; D011829:Radiation Dosage; D011874:Radiometry / Q000379:methods* / Q000706:statistics & numerical data; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D005472:Fluorouracil