Striatal and Extrastriatal MicroPET Imaging of D2/D3 Dopamine Receptors in Rat Brain With [18F] Fallypride and [18F] Desmethoxyfallypride

被引:31
作者
Constantinescu, Cristian C. [1 ]
Coleman, Robert A. [1 ]
Pan, Min-Liang [1 ]
Mukherjee, Jogeshwar [1 ]
机构
[1] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92697 USA
关键词
PET (positron emission tomography); D2; receptors; small animals; preclinical; imaging; BP; striatum; extrastriatal; F-18]fallypride; F-18]desmethoxyfallypride; POSITRON-EMISSION-TOMOGRAPHY; NONHUMAN-PRIMATES; BINDING PARAMETERS; TEST-RETEST; PET; F-18-FALLYPRIDE; QUANTITATION; RADIOLIGAND; VOLUNTEERS; AFFINITY;
D O I
10.1002/syn.20904
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In this study, we compared two different D2/3 receptor ligands, [F-18]fallypride and [F-18] desmethoxyfallypride ([F-18]DMFP) with respect to the duration of the scan, visualization of extrastriatal receptors, and binding potentials (BPND) in the rat brain. In addition, we studied the feasibility of using these tracers following a period of awake tracer uptake, during which the animal may perform a behavioral task. Male Sprague-Dawley rats were imaged with [F-18] fallypride and with [F-18] DMFP in four different studies using microPET. All scans were performed under isoflurane anesthesia. The first (test) and second (retest) study were 150-min baseline scans. No retest scans were performed with [F-18] DMFP. A third study was a 60-min awake uptake of radiotracer followed by a 90-min scan. A fourth study was a 150-min competition scan with haloperidol (0.2 mg/kg) administered via tail vein at 90-min post-[F-18] fallypride injection and 60-min post-[F-18] DMFP. For the test-retest studies, BPND was measured using both Logan noninvasive (LNI) method and the interval ratios (ITR) method. Cerebellum was used as a reference region. For the third study, the binding was measured only with the ITR method, and the results were compared to the baseline results. Studies showed that the average transient equilibrium time in the dorsal striatum (DSTR) was at 90 min for [F-18] fallypride and 30 min for [F-18] DMFP. The average BPND for [F-18] fallypride was 14.4 in DSTR, 6.8 in ventral striatum (VSTR), 1.3 in substantia nigra/ventral tegmental area (SN/VTA), 1.4 in colliculi (COL), and 1.5 in central gray area. In the case of [F-18] DMFP, the average BPND values were 2.2 in DSTR, 2.7 in VSTR, and 0.8 in SN/VTA. The haloperidol blockade showed detectable decrease in binding of both tracers in striatal regions with a faster displacement of [F-18] DMFP. No significant changes in BPND of [F-18] fallypride due to the initial awake state of the animal were found, whereas BPND of [F-18] DMFP was significantly higher in the awake state compared to baseline. We were able to demonstrate that dynamic PET using MicroPET Inveon allows quantification of both striatal and extrastriatal [F-18] fallypride binding in rats in vivo. Quantification of the striatal regions could be achieved with [F-18] DMFP. Synapse 65:778-787, 2011. (C) 2011 Wiley-Liss, Inc.
引用
收藏
页码:778 / 787
页数:10
相关论文
共 27 条
[11]   Comparison of the transient equilibrium and continuous infusion method for quantitative PET analysis of [11C]raclopride binding [J].
Ito, H ;
Hietala, J ;
Blomqvist, G ;
Halldin, C ;
Farde, L .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1998, 18 (09) :941-950
[12]   3-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1H-pyrrolo[2,3-b]pyridine: An antagonist with high affinity and selectivity for the human dopamine D-4 receptor [J].
Kulagowski, JJ ;
Broughton, HB ;
Curtis, NR ;
Mawer, IM ;
Ridgill, MP ;
Baker, R ;
Emms, F ;
Freedman, SB ;
Marwood, R ;
Patel, S ;
Patel, S ;
Ragan, CI ;
Leeson, PD .
JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (10) :1941-1942
[13]   Simplified reference tissue model for PET receptor studies [J].
Lammertsma, AA ;
Hume, SP .
NEUROIMAGE, 1996, 4 (03) :153-158
[14]   Distribution volume ratios without blood sampling from graphical analysis of PET data [J].
Logan, J ;
Fowler, JS ;
Volkow, ND ;
Wang, GJ ;
Ding, YS ;
Alexoff, DL .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1996, 16 (05) :834-840
[15]   Measurement of d-amphetamine-induced effects on the binding of dopamine D-2/D-3 receptor radioligand, 18F-fallypride in extrastriatal brain regions in non-human primates using PET [J].
Mukherjee, J ;
Christian, BT ;
Narayanan, TK ;
Shi, BZ ;
Collins, D .
BRAIN RESEARCH, 2005, 1032 (1-2) :77-84
[16]   FLUORINATED BENZAMIDE NEUROLEPTICS .3. DEVELOPMENT OF (S)-N-[(1-ALLYL-2-PYRROLIDINYL)METHYL]-5-(3-[F-18] FLUOROPROPYL)-2,3-DIMETHOXYBENZAMIDE AS AN IMPROVED DOPAMINE D-2 RECEPTOR TRACER [J].
MUKHERJEE, J ;
YANG, ZY ;
DAS, MK ;
BROWN, T .
NUCLEAR MEDICINE AND BIOLOGY, 1995, 22 (03) :283-296
[17]   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 [J].
Mukherjee, J ;
Christian, BT ;
Dunigan, KA ;
Shi, BZ ;
Narayanan, TK ;
Satter, M ;
Mantil, J .
SYNAPSE, 2002, 46 (03) :170-188
[18]   F-18-desmethoxyfallypride: A fluorine-18 labeled radiotracer with properties similar to carbon-11 raclopride for pet imaging studies of dopamine D-2 receptors [J].
Mukherjee, J ;
Yang, ZY ;
Brown, T ;
Roemer, J ;
Cooper, M .
LIFE SCIENCES, 1996, 59 (08) :669-678
[19]   Imaging dopamine release with Positron Emission Tomography (PET) and 11C-raclopride in freely moving animals [J].
Patel, Vinal D. ;
Lee, Dianne E. ;
Alexoff, David L. ;
Dewey, Stephen L. ;
Schiffer, Wynne K. .
NEUROIMAGE, 2008, 41 (03) :1051-1066
[20]  
Paxinos G., 1997, RAT BRAIN STEROTAXIC, VThird