Evaluation of the metabotropic glutamate receptor subtype 5 using PET and 11C-ABP688: assessment of methods.
(11)C-ABP688 is a new PET ligand to assess the subtype 5 metabotropic glutamate receptor (mGlu(5)). The purpose of this study was to evaluate different methods for the analysis of human (11)C-ABP688 data acquired from 6 healthy, young volunteers.


METHODS
The methods were a 1-tissue-compartment model (K(1), k(2)''), 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'' (= K(1)/k(2)'', 1 tissue compartment); specific DV, DV(C2) (= K(1)/k(2)' x k(3)'/k(4), 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 mGlu(5) receptors. The first-pass extraction fraction exceeded 95%. The minimal scan duration to obtain stable results was estimated to be 45 min.


CONCLUSIONS
(11)C-ABP688 displays favorable kinetics for assessing mGlu(5) 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.
Treyer
Valerie
V
PET Center, Division of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland.
Streffer
Johannes
J
Wyss
Matthias T
MT
Bettio
Andrea
A
Ametamey
Simon M
SM
Fischer
Uta
U
Schmidt
Mark
M
Gasparini
Fabrizio
F
Hock
Christoph
C
Buck
Alfred
A
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005069:Evaluation Studies as Topic; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008954:Models, Biological; D010091:Oximes / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods; D011725:Pyridines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D002250:Carbon Radioisotopes; D010091:Oximes; D011725:Pyridines; D019275:Radiopharmaceuticals; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate