title: Whole-body biodistribution and dosimetry estimates of a novel radiotracer for imaging of serotonin 4 receptors in brain: [¹⁸F]MNI-698.
abstract: BACKGROUND
  A new radiotracer for imaging the serotonin 4 receptors (5-HT4) in brain, [¹⁸F]MNI-698, was recently developed by our group. Evaluation in nonhuman primates indicates the novel radiotracer holds promise as an imaging agent of 5-HT4 in brain. This paper aims to describe the whole-body biodistribution and dosimetry estimates of [¹⁸F]MNI-698.
  
  
  METHODS
  Whole-body positron emission tomography (PET) images were acquired over 240 minutes after intravenous bolus injection of [¹⁸F]MNI-698 in adult rhesus monkeys. Different models were investigated for quantification of radiation absorbed and effective doses using OLINDA/EXM 1.0 software.
  
  
  RESULTS
  The radiotracer main elimination route was found to be urinary and the critical organ was the urinary bladder. Modeling of the urinary bladder voiding interval had a considerable effect on the estimated effective dose. Normalization of rhesus monkeys' organs and whole-body masses to human equivalent reduced the calculated dosimetry values. The effective dose ranged between 0.017 and 0.027 mSv/MBq.
  
  
  CONCLUSIONS
  The dosimetry estimates, obtained when normalizing organ and whole-body weights and applying the urinary bladder model, indicate that the radiation doses from [¹⁸F]MNI-698 comply with limits and guidelines recommended by key regulatory authorities that govern the translation of radiotracers to human clinical trials. The timing of urinary bladder emptying should be considered when designing future clinical protocols with [¹⁸F]MNI-698, in order to minimize the subject absorbed doses.
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, CT, USA. Electronic address: adriana_tavares@msn.com.
authors.forename: Adriana Alexandre S
authors.initials: AA
authors.lastname: Tavares
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, CT, USA; Institute for Neurodegenerative Disorders, New Haven, CT, USA.
authors.forename: Fabien
authors.initials: F
authors.lastname: Caillé
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, CT, USA; Institute for Neurodegenerative Disorders, New Haven, CT, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Barret
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, CT, USA; Institute for Neurodegenerative Disorders, New Haven, CT, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Papin
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, CT, USA; Institute for Neurodegenerative Disorders, New Haven, CT, USA.
authors.forename: Hsiaoju
authors.initials: H
authors.lastname: Lee
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, CT, USA; Institute for Neurodegenerative Disorders, New Haven, CT, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Morley
authors.affiliation: Yale University, New Haven, CT, USA.
authors.forename: Krista
authors.initials: K
authors.lastname: Fowles
authors.affiliation: Yale University, New Haven, CT, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Holden
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, CT, USA; Institute for Neurodegenerative Disorders, New Haven, CT, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Seibyl
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, CT, USA; Institute for Neurodegenerative Disorders, New Haven, CT, USA.
authors.forename: David
authors.initials: D
authors.lastname: Alagille
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, CT, USA; Institute for Neurodegenerative Disorders, New Haven, CT, USA. Electronic address: gtamagnan@mnimaging.com.
authors.forename: Gilles D
authors.initials: GD
authors.lastname: Tamagnan
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004146:Dioxanes / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D010880:Piperidines / Q000493:pharmacokinetics*; D011849:Radioactive Tracers; D011874:Radiometry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism*; D014018:Tissue Distribution; D051598:Whole Body Imaging
chemical_list: C000593529:(1-(2-fluoroethyl)piperidin-4-yl)methyl 8-amino-7-chloro-2,3-dihydrobenzo(b)(1,4)dioxine-5-carboxylate; D004146:Dioxanes; D010880:Piperidines; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; D044422:Receptors, Serotonin, 5-HT4
keywords: 5-HT(4) receptors; Biodistribution; Brain imaging; Dosimetry; [(18)F]MNI-698