Evaluation of the metabotropic glutamate receptor subtype 5 using PET and 11C-ABP688: Assessment of methods

Abstract

11C-ABP688 is a new PET ligand to assess the subtype 5 metabotropic glutamate receptor (mGlu5). The purpose of this study was to evaluate different methods for the analysis of human 11C- ABP688 data acquired from 6 healthy, young volunteers. Methods: The methods were a 1-tissue-compartment model (K1, k2″), a 2-tissue-compartment model (K1-k4), and the noncompartmental method developed by Logan. Parameters related to receptor density were the total distribution volume (DV), DV″ (= K1/k2″, 1 tissue compartment); specific DV, DVC2 (= K1/k2′ x k3′/k4, 2 tissue compartments); and DV tot for the non-compartmental method. Results: The 1-tissue-compartment model was too simple to adequately fit the data. DV C2 calculated with the 2-tissue-compartment model ranged from 5.45 ± 1.47 (anterior cingulate) to 1.91 ± 0.32 (cerebellum). The corresponding values for DVtot, calculated with the 2-tissue-compartment model and the Logan method (in parentheses), were 6.57 ± 1.45 (6.35 ± 1.32) and 2.93 ± 0.53 (2.48 ± 0.40). There was no clear evidence of a region devoid of mGlu5 receptors. The first-pass extraction fraction exceeded 95%. The minimal scan duration to obtain stable results was estimated to be 45 min. Conclusion: 11C-ABP688 displays favorable kinetics for assessing mGlu5 receptors. For tracer kinetic modeling, 2-tissue-compartment models are clearly superior to models with only 1 tissue compartment. In comparison to the compartmental models, the Logan method is equally useful if only DV tot values are required and fast pixelwise parametric maps are desired. The lack of regions devoid of receptors limits the use of reference region methods that do not require arterial blood sampling. Another advantage of the tracer is the fast kinetics that allow for relatively short acquisitions. Copyright © 2007 by the Society of Nuclear Medicine, Inc.