title: Absorbed radiation dosimetry of the D3-specific PET radioligand [18F]FluorTriopride estimated using rodent and nonhuman primate.
abstract: [18F]FluorTriopride ([18F]FTP) is a dopamine D3-receptor preferring radioligand with potential for investigation of neuropsychiatric disorders including Parkinson disease, dystonia and schizophrenia. Here we estimate human radiation dosimetry for [18F]FTP based on theex-vivobiodistribution in rodents andin vivodistribution in nonhuman primates. Biodistribution data were generated using male and female Sprague-Dawley rats injected with ~370 KBq of [18F]FTP and euthanized at 5, 30, 60, 120, and 240 min. Organs of interest were dissected, weighed and assayed for radioactivity content. PET imaging studies were performed in two male and one femalemacaque fascicularisadministered 143-190 MBq of [18F]FTP and scanned whole-body in sequential sections. Organ residence times were calculated based on organ time activity curves (TAC) created from regions of Interest. OLINDA/EXM 1.1 was used to estimate human radiation dosimetry based on scaled organ residence times. In the rodent, the highest absorbed radiation dose was the upper large intestines (0.32-0.49 mGy/MBq), with an effective dose of 0.07 mSv/MBq in males and 0.1 mSv/MBq in females. For the nonhuman primate, however, the gallbladder wall was the critical organ (1.81 mGy/MBq), and the effective dose was 0.02 mSv/MBq. The species discrepancy in dosimetry estimates for [18F]FTP based on rat and primate data can be attributed to the slower transit of tracer through the hepatobiliary track of the primate compared to the rat, which lacks a gallbladder. Out findings demonstrate that the nonhuman primate model is more appropriate model for estimating human absorbed radiation dosimetry when hepatobiliary excretion plays a major role in radiotracer elimination.
authors.affiliation: Mallinckrodt Institute of Radiology, School of Medicine, Washington University St. Louis, MO 63110, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Laforest
authors.affiliation: Department of Neurology, School of Medicine, Washington University St. Louis, MO 63110, USA.
authors.forename: Morvarid
authors.initials: M
authors.lastname: Karimi
authors.affiliation: Mallinckrodt Institute of Radiology, School of Medicine, Washington UniversitySt. Louis, MO 63110, USA; Department of Biochemistry and Molecular Biophysics, School of Medicine, Washington UniversitySt. Louis, MO 63110, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Moerlein
authors.affiliation: Mallinckrodt Institute of Radiology, School of Medicine, Washington UniversitySt. Louis, MO 63110, USA; Department of Biochemistry and Molecular Biophysics, School of Medicine, Washington UniversitySt. Louis, MO 63110, USA.
authors.forename: Jinbin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Neurology, School of Medicine, Washington University St. Louis, MO 63110, USA.
authors.forename: Hubert P
authors.initials: HP
authors.lastname: Flores
authors.affiliation: Mallinckrodt Institute of Radiology, School of Medicine, Washington University St. Louis, MO 63110, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bognar
authors.affiliation: Mallinckrodt Institute of Radiology, School of Medicine, Washington University St. Louis, MO 63110, USA.
authors.forename: Aixiao
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Radiology, Perelman School of Medicine, University of Pennsylvania Philadelphia, PA 19104, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach
authors.affiliation: Mallinckrodt Institute of Radiology, School of Medicine, Washington UniversitySt. Louis, MO 63110, USA; Department of Neurology, School of Medicine, Washington UniversitySt. Louis, MO 63110, USA.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Perlmutter
authors.affiliation: Mallinckrodt Institute of Radiology, School of Medicine, Washington University St. Louis, MO 63110, USA.
authors.forename: Zhude
authors.initials: Z
authors.lastname: Tu
keywords: D3 receptors; Fluorine-18; PET; Parkinson disease; [18F]FluorTriopride; dosimetry