Whole-body biodistribution and dosimetry estimates of a novel radiotracer for imaging of serotonin 4 receptors in brain: [F-18]MNI-698

Adriana Alexandre S. Tavares, Fabien Caille, Olivier Barret, Caroline Papin, Hsiaoju Lee, Thomas J. Morley, Krista Fowles, Daniel Holden, John P. Seibyl, David Alagille, Gilles D. Tamagnan

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: A new radiotracer for imaging the serotonin 4 receptors (5-HT4) in brain, [F-18]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 [F-18]MNI-698.

Methods: Whole-body positron emission tomography (PET) images were acquired over 240 minutes after intravenous bolus injection of [F-18]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.

Conclusion: The dosimetry estimates, obtained when normalizing organ and whole-body weights and applying the urinary bladder model, indicate that the radiation doses from [F-18]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 [F-18]MNI-698, in order to minimize the subject absorbed doses. (C) 2014 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)432-439
Number of pages8
JournalNuclear Medicine and Biology
Volume41
Issue number5
DOIs
Publication statusPublished - 2014

Keywords

  • 5-HT4 receptors
  • Brain imaging
  • [F-18]MNI-698
  • Dosimetry
  • Biodistribution
  • POSITRON-EMISSION-TOMOGRAPHY
  • 5-HT4 RECEPTORS
  • IN-VIVO
  • RADIATION-DOSIMETRY
  • PET RADIOLIGAND
  • RATS
  • PHARMACOLOGY
  • ENHANCEMENT
  • ACTIVATION
  • AGONIST

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