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Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [11C]SNAP-7941
Published on: April 28, 2019
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.
Purpose:
Preclinical positron emission tomography studies are important to follow disease progression and develop new pharmacological agents. We investigated whether kinetic modeling of 5-HT2A tracer [(11)C]MDL 100907 is possible in rats.
Procedures And Results:
Kinetic modeling with either metabolite-corrected plasma curve or with the cerebellum as a reference tissue resulted in a good correlation of nondisplaceable binding potential (BPND) calculated from a two-tissue compartment model (2TCM) or different reference tissue models. Injecting the tracer by a slower bolus decreases the variation in 2TCM outcome parameters and results in a good correlation between k3/k4 and the other models. Application of 0.2 mg/kg cold MDL 100907 resulted in almost complete occupancy of 5-HT2A receptors.
Conclusions:
A reference tissue model can be used for [(11)C]MDL kinetic modeling in rats, which is preferable in pharmacological or longitudinal studies.
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.

