Vandehey, Nicholas T;
Moirano, Jeffrey M;
Converse, Alexander K;
Holden, James E;
Mukherjee, Jogesh;
Murali, Dhanabalan;
Nickles, R Jerry;
Davidson, Richard J;
Schneider, Mary L;
Christian, Bradley T
High-Affinity Dopamine D2/D3 PET Radioligands 18F-Fallypride and 11C-FLB457: A Comparison of Kinetics in Extrastriatal Regions Using a Multiple-Injection Protocol
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Media type:
E-Article
Title:
High-Affinity Dopamine D2/D3 PET Radioligands 18F-Fallypride and 11C-FLB457: A Comparison of Kinetics in Extrastriatal Regions Using a Multiple-Injection Protocol
Contributor:
Vandehey, Nicholas T;
Moirano, Jeffrey M;
Converse, Alexander K;
Holden, James E;
Mukherjee, Jogesh;
Murali, Dhanabalan;
Nickles, R Jerry;
Davidson, Richard J;
Schneider, Mary L;
Christian, Bradley T
Published:
SAGE Publications, 2010
Published in:
Journal of Cerebral Blood Flow & Metabolism, 30 (2010) 5, Seite 994-1007
Description:
<jats:p> <jats:sup>18</jats:sup>F-Fallypride and <jats:sup>11</jats:sup>C-FLB457 are commonly used PET radioligands for imaging extrastriatal dopamine D<jats:sub>2</jats:sub>/D<jats:sub>3</jats:sub> receptors, but differences in their in vivo kinetics may affect the sensitivity for measuring subtle changes in receptor binding. Focusing on regions of low binding, a direct comparison of the kinetics of <jats:sup>18</jats:sup>F-fallypride and <jats:sup>11</jats:sup>C-FLB457 was made using a MI protocol. Injection protocols were designed to estimate K<jats:sub>1</jats:sub>, k<jats:sub>2</jats:sub>, f<jats:sub>ND</jats:sub> k<jats:sub>on</jats:sub>, B<jats:sub>max</jats:sub>, and k<jats:sub>off</jats:sub> in the midbrain and cortical regions of the rhesus monkey. <jats:sup>11</jats:sup>C-FLB457 cleared from the arterial plasma faster and yielded a ND space distribution volume ( K<jats:sub>1</jats:sub>/ k<jats:sub>2</jats:sub>) that is three times higher than <jats:sup>18</jats:sup>F-fallypride, primarily due to a slower k<jats:sub>2</jats:sub> (FAL:FLB; k<jats:sub>2</jats:sub>=0.54 min<jats:sup>−1</jats:sup>:0.18 min<jats:sup>−1</jats:sup>). The dissociation rate constant, k<jats:sub>off</jats:sub>, was slower for <jats:sup>11</jats:sup>C-FLB457, resulting in a lower K<jats:sub>Dapp</jats:sub> than <jats:sup>18</jats:sup>F-fallypride (FAL:FLB; 0.39 nM:0.13 nM). Specific D<jats:sub>2</jats:sub>/D<jats:sub>3</jats:sub> binding could be detected in the cerebellum for <jats:sup>11</jats:sup>C-FLB457 but not <jats:sup>18</jats:sup>F-fallypride. Both radioligands can be used to image extrastriatal D<jats:sub>2</jats:sub>/D<jats:sub>3</jats:sub> receptors, with <jats:sup>11</jats:sup>C-FLB457 providing greater sensitivity to subtle changes in low-receptor-density cortical regions and <jats:sup>18</jats:sup>F-fallypride being more sensitive to endogenous dopamine displacement in medium-to-high-receptor-density regions. In the presence of specific D<jats:sub>2</jats:sub>/D<jats:sub>3</jats:sub> binding in the cerebellum, reference region analysis methods will give a greater bias in BP<jats:sub>ND</jats:sub> with <jats:sup>11</jats:sup>C-FLB457 than with <jats:sup>18</jats:sup>F-fallypride. </jats:p>