Evaluation of [ 18 F]FNM biodistribution and dosimetry based on whole-body PET imaging of rats

Nucl Med Biol. 2018 Apr;59:1-8. doi: 10.1016/j.nucmedbio.2017.12.003. Epub 2017 Dec 21.

Abstract

Introduction: The aim of this work was to study the biodistribution, metabolism and radiation dosimetry of rats injected with [18F]FNM using PET/CT images. This novel radiotracer targeting NMDA receptor has potential for investigation for neurological and psychiatric diseases.

Methods: Free fraction and stability in fresh human plasma were determined in vitro. PET/CT was performed on anesthetized rats. Organs were identified and 3D volumes of interest (VOIs) were manually drawn on the CT in the center of each organ. Time activity curves (TACs) were created with these VOIs, enabling the calculation of residence times. To confirm these values, ex vivo measurements of organs were performed. Plasma and urine were also collected to study in vivo metabolism. Data was extrapolated to humans, effective doses were estimated using ICRP-60 and ICRP-89 dosimetric models and absorbed doses were estimated using OLINDA/EXM V1.0 and OLINDA/EXM V2.0 (which use weighting factors from ICRP-103 to do the calculations).

Results: The [18F]FNM was stable in human plasma and the diffusible free fraction was 53%. As with memantine, this tracer is poorly metabolized in vivo. Ex vivo distributions validated PET/CT data as well as demonstrating a decrease of radiotracer uptake in the brain due to anesthesia. Total effective dose was around 6.11 μSv/MBq and 4.65 μSv/MBq for female and male human dosimetric models, respectively.

Conclusions: This study shows that the presented compound exhibits stability in plasma and plasma protein binding very similar to memantine. Its dosimetry shows that it is suitable for use in humans due to a low total effective dose compared to other PET radiotracers.

Keywords: Dosimetry; NMDA receptor; OLINDA; Position emission tomography (PET); [(18)F]FNM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Proteins / metabolism
  • Drug Stability
  • Female
  • Humans
  • Memantine / analogs & derivatives*
  • Memantine / chemical synthesis
  • Memantine / metabolism
  • Memantine / pharmacokinetics
  • Positron Emission Tomography Computed Tomography*
  • Radiometry
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution
  • Whole Body Imaging*

Substances

  • Blood Proteins
  • fluoroethylnormemantine
  • Memantine