Analysis of 5-HT(2A) receptor binding with [(11)C]MDL 100907 in rats: optimization of kinetic modeling

Anniek K D Visser1, Erik F J De Vries, Nisha K Ramakrishnan

  • 1Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands, visserakd@umcg.nl.

Abstract

Insights

Kinetic modeling of the serotonin 5-HT2A receptor tracer [(11)C]MDL 100907 is feasible in rats. A reference tissue model provides reliable results for preclinical positron emission tomography studies.

Area of Science:

  • Neuroscience
  • Radiochemistry
  • Pharmacology

Background:

  • Preclinical positron emission tomography (PET) is crucial for tracking disease progression and evaluating new drugs.
  • Understanding serotonin 5-HT2A receptor kinetics is vital for neurological research.

Purpose of the Study:

  • To determine the feasibility of kinetic modeling for the 5-HT2A tracer [(11)C]MDL 100907 in a rat model.
  • To assess the reliability of different kinetic modeling approaches for this tracer.

Main Methods:

  • Investigated kinetic modeling of [(11)C]MDL 100907 in rats using PET.
  • Compared metabolite-corrected plasma curves and reference tissue models (e.g., cerebellum).
  • Evaluated the impact of tracer injection method and receptor occupancy on modeling outcomes.

Main Results:

  • Good correlation was observed between nondisplaceable binding potential (BPND) values derived from two-tissue compartment models (2TCM) and reference tissue models.
  • Slower tracer bolus injection reduced variability in 2TCM parameters and improved correlation with other models.
  • A dose of 0.2 mg/kg cold MDL 100907 achieved near-complete 5-HT2A receptor occupancy.

Conclusions:

  • A reference tissue model is suitable for [(11)C]MDL 100907 kinetic modeling in rats.
  • This approach is advantageous for pharmacological and longitudinal preclinical studies.
  • The findings support the use of [(11)C]MDL 100907 for in vivo 5-HT2A receptor research in rats.