High-Affinity Dopamine D2/D3 PET Radioligands 18F-Fallypride and 11C-FLB457: A Comparison of Kinetics in Extrastriatal Regions Using a Multiple-Injection Protocol
| Autor: | James E. Holden, R. Jerry Nickles, Jogesh Mukherjee, Dhanabalan Murali, Jeffrey M. Moirano, Richard J. Davidson, Bradley T. Christian, Mary L. Schneider, Alexander K. Converse, Nicholas T. Vandehey |
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| Rok vydání: | 2009 |
| Předmět: |
Fluorine Radioisotopes
medicine.medical_specialty Cerebellum Pyrrolidines Ligands Midbrain chemistry.chemical_compound Dopamine Dopamine receptor D2 Internal medicine Salicylamides medicine Animals Carbon Radioisotopes Neurotransmitter Receptor Receptors Dopamine D2 Chemistry Receptors Dopamine D3 Brain Macaca mulatta Endocrinology medicine.anatomical_structure Neurology Fallypride Positron-Emission Tomography Benzamides Biophysics Catecholamine Dopamine Antagonists Original Article Neurology (clinical) Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 30:994-1007 |
| ISSN: | 1559-7016 0271-678X |
| Popis: | 18F-Fallypride and 11C-FLB457 are commonly used PET radioligands for imaging extrastriatal dopamine D2/D3 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 18F-fallypride and 11C-FLB457 was made using a MI protocol. Injection protocols were designed to estimate K1, k2, fND kon, Bmax, and koff in the midbrain and cortical regions of the rhesus monkey. 11C-FLB457 cleared from the arterial plasma faster and yielded a ND space distribution volume ( K1/ k2) that is three times higher than 18F-fallypride, primarily due to a slower k2 (FAL:FLB; k2=0.54 min−1:0.18 min−1). The dissociation rate constant, koff, was slower for 11C-FLB457, resulting in a lower KDapp than 18F-fallypride (FAL:FLB; 0.39 nM:0.13 nM). Specific D2/D3 binding could be detected in the cerebellum for 11C-FLB457 but not 18F-fallypride. Both radioligands can be used to image extrastriatal D2/D3 receptors, with 11C-FLB457 providing greater sensitivity to subtle changes in low-receptor-density cortical regions and 18F-fallypride being more sensitive to endogenous dopamine displacement in medium-to-high-receptor-density regions. In the presence of specific D2/D3 binding in the cerebellum, reference region analysis methods will give a greater bias in BPND with 11C-FLB457 than with 18F-fallypride. |
| Databáze: | OpenAIRE |
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