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Brain imaging of 18 F‐fallypride in normal volunteers: Blood analysis, distribution, test‐retest studies, and preliminary assessment of sensitivity to aging effects on dopamine D‐2/D‐3 receptors
Author(s) -
Mukherjee Jogeshwar,
Christian Bradley T.,
Dunigan Kelly A.,
Shi Bingzhi,
Narayanan Tanjore K.,
Satter Martin,
Mantil Joseph
Publication year - 2002
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10128
Subject(s) - putamen , orbitofrontal cortex , nuclear medicine , temporal cortex , dopamine receptor d3 , entorhinal cortex , hippocampus , cortex (anatomy) , medicine , neuroscience , dopamine , psychology , dopamine receptor , prefrontal cortex , cognition
Human studies of dopamine D2/D3 receptors using 18 F‐fallypride‐PET in normal volunteers were performed to evaluate brain distribution in striatal and extrastriatal regions, evaluate metabolites in blood plasma, establish PET imaging protocol for this new radiotracer, evaluate graphical methods of analysis to quantitate D2/D3 receptors, and assess the ability of 18 F‐fallypride to measure changes in D2/D3 receptors with aging as a model. Subjects (6; 21–63 years) had a PET scan on a Siemens HR+ scanner with 18 F‐fallypride and a T1‐weighted MRI scan on a 1.5T GE scanner for purposes of anatomical coregistration with PET. A 3‐h PET scan with 18 F‐fallypride (0.07 mCi/Kg) was carried out on each subject and repeated in 4–6 weeks. Arterial or arterialized venous blood was obtained in all subjects in order to evaluate blood activity levels and analyze metabolites in the plasma. Brain regions‐of‐interest were identified and drawn using PET and PET‐MR coregistered images. PET data was analyzed using graphical methods in which cerebellum was used as the reference region providing distribution volume ratios (DVR) from which binding potential (BP) was derived and used as a measure of concentration of receptors. Distribution of 18 F‐fallypride was consistent in all subjects studied and the rank order of receptor concentration was putamen > caudate > thalamus = pituitary > amygdala > colliculi > substantia nigra > hippocampus = temporal cortex > parietal cortex = occipital cortex = orbitofrontal cortex. For younger subjects, BP ranged from 37 for the putamen to 0.4 for orbitofrontal cortex, with a test–retest error of about 10%. Both hydrophilic and lipophilic metabolites were observed in arterial blood plasma and analyses showed approx. 30–40% of plasma radioactivity at 3 h was 18 F‐fallypride. With aging, all brain regions exhibited a significant decrease (>10% per decade) in binding of 18 F‐fallypride. PET studies with 18 F‐fallypride are thus suitable to study changes in D2/D3 receptors in striatal and extrastriatal brain regions. Synapse 46:170–188, 2002. © 2002 Wiley‐Liss, Inc.