Evaluation of the Metabotropic Glutamate Receptor Subtype 5 Using PET and ¹¹C-ABP688: Assessment of Methods

¹ PET Center, Division of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland
² Division of Psychiatry Research, University of Zurich, Zurich, Switzerland
³ Center for Radiopharmaceutical Science of ETH, PSI, and USZ, Department of Chemistry and Applied Biosciences of ETH, Zurich, Zurich, Switzerland
⁴ Novartis Pharma AG, Basel, Switzerland
⁵ Novartis Institutes for Biomedical Research, Basel, Switzerland

^* To whom correspondence should be addressed. E-mail: fred.buck{at}usz.ch.

	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, DV_C2 (= K₁/k₂' x k₃'/k₄, 2 tissue compartments); and DV_tot for the noncompartmental 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 DV_tot, 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.

Key Words: positron emission tomography, kinetic modeling, molecular imaging, mGlu₅, ¹¹C-ABP688

This article has been cited by other articles:

				C. J. Endres, M. G. Pomper, M. James, O. Uzuner, D. A. Hammoud, C. C. Watkins, A. Reynolds, J. Hilton, R. F. Dannals, and M. Kassiou Initial Evaluation of 11C-DPA-713, a Novel TSPO PET Ligand, in Humans J. Nucl. Med., August 1, 2009; 50(8): 1276 - 1282. [Abstract] [Full Text] [PDF]