In vivo evaluation of radiotracers targeting the melanin-concentrating hormone receptor 1: [11C]SNAP-7941 and [18F]FE@SNAP reveal specific uptake in the ventricular system

Sci Rep. 2017 Aug 14;7(1):8054. doi: 10.1038/s41598-017-08684-6.

Abstract

The MCHR1 is involved in the regulation of energy homeostasis and changes of the expression are linked to a variety of associated diseases, such as diabetes and adiposity. The study aimed at the in vitro and in vivo evaluation of [11C]SNAP-7941 and [18F]FE@SNAP as potential PET-tracers for the MCHR1. Competitive binding studies with non-radioactive derivatives and small-animal PET/CT and MRI brain studies were performed under baseline conditions and tracer displacement with the unlabelled MCHR1 antagonist (±)-SNAP-7941. Binding studies evinced high binding affinity of the non-radioactive derivatives. Small-animal imaging of [11C]SNAP-7941 and [18F]FE@SNAP evinced high tracer uptake in MCHR1-rich regions of the ventricular system. Quantitative analysis depicted a significant tracer reduction after displacement with (±)-SNAP-7941. Due to the high binding affinity of the non-labelled derivatives and the high specific tracer uptake of [11C]SNAP-7941 and [18F]FE@SNAP, there is strong evidence that both radiotracers may serve as highly suitable agents for specific MCHR1 imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Radioisotopes / metabolism*
  • Cerebral Ventricles / metabolism*
  • Evaluation Studies as Topic
  • Fluorine Radioisotopes / metabolism*
  • Magnetic Resonance Imaging / methods
  • Male
  • Piperidines / metabolism*
  • Positron Emission Tomography Computed Tomography / methods
  • Pyrimidines / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Somatostatin / metabolism*

Substances

  • Carbon Radioisotopes
  • Carbon-11
  • Fluorine Radioisotopes
  • MCHR1 protein, rat
  • Piperidines
  • Pyrimidines
  • Receptors, Somatostatin
  • SNAP7941
  • Fluorine-18