In vivo affinity of [18F]fallypride for striatal and extrastriatal dopamine D2 receptors in nonhuman primates.
BACKGROUND
[18F]Fallypride is a new and promising radiotracer, suitable for imaging D2 receptors with Positron Emission Tomography (PET) in both striatal and extrastriatal regions. The high signal to noise ratio of [18F]fallypride has been attributed to its high affinity for D2 receptors (K(D) of 0.03 nM, measured in vitro at room temperature).


OBJECTIVE
We sought to further characterize this tracer in terms of its in vivo affinity, possible affinity differences between brain regions and dependence of in vitro affinity on temperature.


METHODS
PET scans were performed in baboons over a wide range of concentrations to measure the in vivo K(D) of [18F]fallypride in striatal and extrastriatal regions. Several analytical approaches were used, including nonlinear kinetic modeling and equilibrium methods. Also, in vitro assays were performed at 22 and 37 degrees C.


RESULTS
No significant differences in the in vivo K(D) were detected between regions. In vivo K(D) of [18F]fallypride was 0.22+/-0.05 nM in striatum, 0.17+/-0.05 nM in thalamus, and 0.21+/-0.07 nM in hippocampus. These values were intermediate between in vitro K(D) measured at 22 (0.04+/-0.03 nM) and 37 degrees (2.03+/-1.07 nM).


CONCLUSIONS
The in vivo affinity of [18F]fallypride was not as high as previously estimated from in vitro values. This property might contribute to the favorable kinetic properties of the tracer. The in vivo affinity was similar between striatal and extrastriatal regions. This result indicates that the measured regional in vivo affinities of this tracer are not affected by putative regional differences in endogenous dopamine, and that [18F]fallypride is an appropriate tool to provide unbiased estimates of the occupancy of D2 receptors by antipsychotic drugs in striatal and extrastriatal regions.
Slifstein
Mark
M
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA. mms218@columbia.edu
Hwang
Dah-Ren
DR
Huang
Yiyun
Y
Guo
Ningning
N
Sudo
Yasuhiko
Y
Narendran
Raj
R
Talbot
Peter
P
Laruelle
Marc
M
D000818:Animals; D001549:Benzamides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D066298:In Vitro Techniques; D008297:Male; D009928:Organ Specificity; D010215:Papio; D049268:Positron-Emission Tomography / Q000379:methods; D011759:Pyrrolidines / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
D001549:Benzamides; D005462:Fluorine Radioisotopes; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2