Quantification of dopamine D(2/3) receptors in rat brain using factor analysis corrected [18F]Fallypride images.
The goal of this work is to quantify the binding parameters of [(18)F]Fallypride in the striatal and extrastriatal regions of the rat brain using factor analysis (FA) to correct small animal PET kinetic imaging for spillover defluorination radioactivity. Eleven rats were employed for YAP-(S)PET acquisitions and metabolite studies. All kinetic parameters including B'(max) and K(d)V(R) were estimated with a three-tissue compartment seven-parameter model (3T-7k) on the basis of all the FA-corrected data from the multi-injection protocol. Binding potential (BP(ND)) was calculated with Logan's graphical analysis taking cerebellum as the reference region and using the first injection raw (BP(ND-RAW)) and FA-corrected (BP(ND-FA)) data. Three distinct factors corresponding to free+non-specific binding, specific binding and skull and gland accumulation were recovered from FA with their corresponding spatial distributions. The resulting reconstructed images without skull and gland accumulation were improved to provide a better contrast between specific and non-specific regions. Very bad fits were obtained when using time-activity curves (TACs) calculated from the raw [(18)F]Fallypride data, whereas all TACs were well fitted by the 3T-7k model after FA correction. FA-corrected data enables the cerebellar region to be used as reference for the Logan approach. The magnitude of the BP(ND-FA) values was increased from 21% to 108% across regions and the rank order of BP(ND-FA) values (Cx<Hip<MB≈Thal<VST<DST) matched those of B'(max) values. This [(18)F]Fallypride study in rats shows that all brain regions are contaminated by skull and gland radioactivity accumulation. We show that FA is a very effective method of correcting kinetic data for spillover activity. Moreover, the approach presented here with [(18)F]Fallypride data can be extended to other radioligands and also to human data which can be highly distorted by radiodefluorination as shown in the literature.
Clinical Neurophysiology and Neuroimaging Unit, Division of Neuropsychiatry, Department of Psychiatry, University Hospitals of Geneva, Switzerland. Philippe.Millet@hcuge.ch
Philippe
P
Millet
Marcelle
M
Moulin-Sallanon
Benjamin B
BB
Tournier
Noé
N
Dumas
Yves
Y
Charnay
Vicente
V
Ibáñez
Nathalie
N
Ginovart
D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D001923:Brain Chemistry; D005163:Factor Analysis, Statistical; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000032:analysis*; D050637:Receptors, Dopamine D3 / Q000032:analysis*; D014018:Tissue Distribution
D001549:Benzamides; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C574003:fallypride