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

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.