Brain imaging of 18F‐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

Synapse - Tập 46 Số 3 - Trang 170-188 - 2002
Jogeshwar Mukherjee1,2, Bradley T. Christian2, Kelly Dunigan2, Bingzhi Shi2, Tanjore K. Narayanan2, Martin Satter2, Joseph Mantil2
1Brain Imaging Center, 162 Irvine Hall, Department of Psychiatry & Human Behavior, University of California‐Irvine, Irvine, CA 92697‐3960
2Department of Nuclear Medicine/PET, Kettering Medical Center, Dayton, Ohio 45429

Tóm tắt

AbstractHuman studies of dopamine D2/D3 receptors using 18F‐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 18F‐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 18F‐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 18F‐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 18F‐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 18F‐fallypride. With aging, all brain regions exhibited a significant decrease (>10% per decade) in binding of 18F‐fallypride. PET studies with 18F‐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.

Từ khóa


Tài liệu tham khảo

Abi‐Dargham A, 2000, Quantitative analysis of striatal and extrastriatal D2 receptors in humans with 18F‐fallypride: validation and reproducibility, Neuroimage, 11, S43

Agid Y, 1987, Biochemistry of neurotransmitters in Parkinson's disease, Mov Disord, 2, 166

10.1016/S0893-133X(97)00112-7

10.1210/edrv-13-2-220

10.1016/0306-4522(87)90008-X

Brix G, 1997, Performance evaluation of a whole‐body PET scanner using the NEMA protocol, J Nucl Med, 38, 1614

Buchholz HG, 2001, In vivo quantification of dopamine D2 receptor binding using PET: comparison of parametric images with ROI based quantification methods applied to PET ligands with different affinity, J Nucl Med, 42, 218P

10.1016/S0014-2999(99)00824-9

10.1093/schbul/16.3.425

10.1002/1098-2396(200010)38:1<71::AID-SYN8>3.0.CO;2-2

10.1007/s002590050358

10.1016/S0262-8856(00)00101-3

10.1016/S0006-3223(00)01038-6

10.1038/jcbfm.1989.98

10.1007/s002130050420

Feldman RS, 1997, Principles of neuropsychopharmacology, 303

10.1016/0306-4522(96)00132-7

10.1001/archpsyc.1997.01830190077008

10.1016/S0893-133X(98)00066-9

10.1038/sj.npp.1380111

10.1007/s002130050131

10.1002/(SICI)1098-2396(199606)23:2<115::AID-SYN7>3.0.CO;2-C

10.1002/(SICI)1098-2396(199611)24:3<224::AID-SYN4>3.0.CO;2-G

Ichise M, 1998, Age‐related changes in D2 receptor binding with iodine‐123‐iodobenzofuran, J Nucl Med, 39, 1511

10.1006/nimg.2000.0717

10.1523/JNEUROSCI.21-02-00676.2001

Janowski A, 1992, Extrastriatal dopamine D2 receptors: distribution, pharmacological characterization and region‐specific regulation by clozapine, J Pharmacol Exp Ther, 261, 1282

Joyce JN, 1994, Dopamine receptors and transporters: pharmacology, structure and function, 345

10.1016/0006-8993(85)90149-0

10.1016/0304-3940(93)90199-U

10.1016/S0006-8993(97)01005-6

10.1016/S0197-4580(00)00149-4

10.1176/appi.ajp.158.2.308

10.1002/(SICI)1096-9861(19981221)402:3<353::AID-CNE5>3.0.CO;2-4

10.1016/0006-8993(93)90878-Q

Kessler RM, 2000, 18F‐N‐ally‐5‐fluorproplepidepride (Fallypride): radiation dosimetry, quantification of striatal and extrastriatal dopamine receptors in man, Neuroimage, 11, S32

10.1016/0165-6147(92)90060-J

Kung HF, 1990, In vivo SPECT imaging of CNS D‐2 dopamine receptors: initial studies with iodine‐123 IBZM in humans, J Nucl Med, 31, 573

10.1097/00006231-199808000-00009

10.1073/pnas.86.16.6412

10.1016/0969-8051(96)00078-9

10.1016/S0969-8051(00)00137-2

10.1097/00004647-199609000-00008

Mai J, 1997, Atlas of the human brain

10.1016/S0893-133X(99)00139-6

10.1016/S0006-8993(00)03211-X

10.1002/ana.410150302

10.1016/0969-8051(94)00117-3

10.1016/S0969-8051(99)00012-8

10.1007/BF00496365

10.1006/nimg.1999.0502

Pohjalainen T, 1998, Sex differences in the striatal dopamine D2 receptor binding characteristics in vivo, Am J Psychiatry, 155, 768

10.1016/0893-133X(87)90004-2

10.1016/S0047-6374(00)00147-0

10.1006/nimg.2001.0761

ThompsonCJ KecaniS BoelenS.2000.Evaluation of a neck‐shield for use during neurological studies with a whole‐body PET scanner. IEEE Med Image Conference Lyon France.

10.1016/S0304-3940(98)00080-9

10.1007/s002130051163

10.1007/s002590000342

Volkow ND, 1993, Reproducibility of repeated measures of carbon‐11 raclopride binding in the human brain, J Nucl Med, 34, 609

Volkow ND, 1998, Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals, Am J Psychiat, 155, 344

10.1097/00004728-199707000-00007

Widman M, 1993, Disposition of remoxipride in different species. Species differences in metabolism, Arzneim‐Forsch/Drug Res, 43, 287

10.1097/00004728-199207000-00024

Thông tin
Thông tin xuất bản

Synapse

Tập 46 Số 3

170-188

Thông tin tác giả