In vivo affinity of [18F]fallypride for striatal and extrastriatal dopamine D2 receptors in nonhuman primates

Slifstein, Mark; Hwang, Dah‐Ren; Huang, Yiyun; Guo, Ningning; Sudo, Yasuhiko; Narendran, Raj; Talbot, Peter S.; Laruelle, Marc

doi:10.1007/s00213-004-1830-x

Cited by 66 publications

(60 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…18 F]fallypride from in vivo imaging data in baboons has shown its affinity to be more on the order of 10-fold higher than that of [ 11 C]raclopride (Slifstein et al, 2004), a result that is consistent with quantitative comparison between these ligands from our own imaging data in humans (Abi-Dargham et al, 2000a;Mawlawi et al, 2001). These results show that while rodent and in vitro studies may be appropriate for proof of concept, quantitative information about radioligand binding in humans is more appropriately derived from in vivo studies in humans and nonhuman primates.…”

Section: Relationship Between In Vitro and In Vivo Studiessupporting

confidence: 80%

[¹¹C]NNC 112 Selectivity for Dopamine D₁and Serotonin 5-HT_2AReceptors: A PET Study in Healthy Human Subjects

Slifstein

Kegeles

Gonzales³

et al. 2007

J Cereb Blood Flow Metab

Self Cite

View full text Add to dashboard Cite

The dopamine D 1 receptor antagonist radioligand [11 C]NNC 112 has previously been reported to have 100-fold selectivity for the D 1 receptor compared with the serotonin 5-HT 2A receptor. In this study, we tested the selectivity by scanning seven healthy human research volunteers with [11 C]NNC 112 before and after 2 mg of the antipsychotic drug risperidone, a dose that putatively blocks all 5-HT 2A receptors with negligible effect on D 1 receptors. We found that specific binding in cortical regions was reduced by 20% to 30%, whereas the striatum showed no change. Based on the known relative densities of these receptors in humans, our results suggest 5-to 10-fold selectivity of [ 11 C]NNC 112 for D 1 versus 5-HT 2A as opposed to 100-fold selectivity. These results suggest caution in interpreting data from studies using this tracer to measure cortical D 1 receptors as well as the need for more selective radioligands to assess cortical D 1 receptors.

show abstract

Section: Relationship Between In Vitro and In Vivo Studiessupporting

confidence: 80%

[¹¹C]NNC 112 Selectivity for Dopamine D₁and Serotonin 5-HT_2AReceptors: A PET Study in Healthy Human Subjects

Slifstein

Kegeles

Gonzales³

et al. 2007

J Cereb Blood Flow Metab

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the saline control monkeys, BPs of both D2 receptors and DAT for the caudate, putamen and substantia nigra were within accepted ranges comparable to previous research (Slifstein et al 2004;Mukherjee et al 2002;Siessmeier et al 2005;Carbon et al 2004). The BP values of D2 receptors in the ACC of the control monkeys were on the higher end of reported BP ranges, but still comparable (Suhara et al 2002;Hagelberg et al 2004;Talvik et al 2003;Kaasinen et al 2000).…”

Section: Effect Of Prenatal Cocaine Exposuresupporting

confidence: 87%

“…[ 18 F]fallypride ( Figure 1a) is a radioactive tracer molecule that binds to both striatal and cortical dopamine D2 and D3 receptors. 1 Due to its high affinity for D2 and D3 receptors, fallypride provides for a higher signal-to-noise ratio than other D2-like ligands (Slifstein et al 2004). [ 18 F]FECNT (Figure 1b) is a radioactive dopamine transporter (DAT) probe.…”

Section: Figurementioning

confidence: 99%

Effect of Prenatal Cocaine Exposure on D2 Receptors and DAT in Rhesus Macaques

Pryweller¹

2006

VURJ

View full text Add to dashboard Cite

Five adult rhesus monkeys with a history of prenatal cocaine exposure (PNCE) region was implemented in the PMOD software package to determine ligand binding potentials for D2/D3 receptors and dopamine transporters (DAT) in each of the ROIs to test whether fallypride and/or FECNT binding potentials, measures of D2/D3 and DAT levels respectively, were influenced by prenatal cocaine exposure. Preliminary results suggest a trend of reduced D2/D3 binding potential with increased PNCE, but future research is necessary.Despite some variability amongst individual studies, a consensus is emerging that prenatal cocaine exposure (PNCE) can have dose dependent effects on the development of dopaminergic circuits . A range of impairments, including deficits in recognition memory, processing speed, task persistence, arousal, distractibility, and stress-responsiveness, have been reported in infants and children exposed to cocaine in utero (Azuma et

show abstract

“…Whereas monkey PET studies found striatum-to-cerebellum ratios ranging from 3 to 9, depending on the time frame (6,21,23), prolonged recordings 18 F-fallypride gave BP ND estimates of 27 (24) and 23 (25). Thus, results in the monkey compare well with those in the human brain (26)(27)(28), as expected for the primate striatum, which is 10-to 20-fold larger than in rodents.…”

Section: Discussionmentioning

confidence: 53%

Validation of the Octamouse for Simultaneous ¹⁸F-Fallypride Small-Animal PET Recordings from 8 Mice

Rominger¹,

Mille²,

Zhang³

et al. 2010

J Nucl Med

View full text Add to dashboard Cite

Data collection in preclinical small-animal PET studies has been hindered by the small number of recordings typically obtained for a single radiosynthesis. Therefore, we tested procedures for obtaining 8 simultaneous small-animal PET recordings from the brains of 8 mice using an acrylic anesthesia distributor (the Octamouse), with the dopamine D 2/3 ligand 18 F-fallypride serving as a test substance for brain receptor imaging. Methods: The effect of scatter correction on the small-animal PET recordings was first evaluated in phantom studies in which sources of different radioactivity concentration were placed within the chambers of the Octamouse. Next, potential effects of mass on the 18 F-fallypride binding potential (BP ND ) in the striatum were tested in groups of mice receiving 18 F-fallypride at 2 different specific activities (140 and 50 GBq/mmol), with and without scatter correction. Finally, the relationship between BP ND and injected dose of 18 F-fallypride (3.5-17 MBq/mouse) was tested. Results: Scatter correction improved the contrast between sources and air space within the Octamouse phantom. The magnitude of 18 F-fallypride BP ND in mouse striatum was invariant across the tested range of specific activities, and scatter correction increased BP ND by a mean of 6%; covariances of the inter-and intraoperator variability of BP ND were 10%. There was a positive correlation between radiochemical dose and BP ND with (R 2 5 0.53) and without (R 2 5 0.63) scatter correction, which was driven by increasing area under the percentage injected dose curve in the striatum. Conclusion: The quantitation of emission sources placed within the Octamouse is linear over a wide range of source activities. In the striatum of living mice, the magnitude of 18 F-fallypride BP ND was highly reproducible between operators and was constant over a 3-fold range of specific activities, indicating a lack of significant occupancy. Scatter correction improved quantitation but did not entirely correct for the dependence of BP ND on injected dose, which was deemed to arise because of effects propagating from detector dead time when the total radiochemical dose in the field of view exceeded 50 MBq. Given this consideration, we were still able to quantify 18 F-fallypride BP ND in 16 mice from a single radiosynthesis, an economy that should be generalizable to brain studies of diverse radioligands.

show abstract

In vivo affinity of [18F]fallypride for striatal and extrastriatal dopamine D2 receptors in nonhuman primates

Cited by 66 publications

References 51 publications

[¹¹C]NNC 112 Selectivity for Dopamine D₁and Serotonin 5-HT_2AReceptors: A PET Study in Healthy Human Subjects

[¹¹C]NNC 112 Selectivity for Dopamine D₁and Serotonin 5-HT_2AReceptors: A PET Study in Healthy Human Subjects

Effect of Prenatal Cocaine Exposure on D2 Receptors and DAT in Rhesus Macaques

Validation of the Octamouse for Simultaneous ¹⁸F-Fallypride Small-Animal PET Recordings from 8 Mice

Contact Info

Product

Resources

About

In vivo affinity of [18F]fallypride for striatal and extrastriatal dopamine D2 receptors in nonhuman primates

Cited by 66 publications

References 51 publications

[11C]NNC 112 Selectivity for Dopamine D1and Serotonin 5-HT2AReceptors: A PET Study in Healthy Human Subjects

[11C]NNC 112 Selectivity for Dopamine D1and Serotonin 5-HT2AReceptors: A PET Study in Healthy Human Subjects

Effect of Prenatal Cocaine Exposure on D2 Receptors and DAT in Rhesus Macaques

Validation of the Octamouse for Simultaneous 18F-Fallypride Small-Animal PET Recordings from 8 Mice

Contact Info

Product

Resources

About

[¹¹C]NNC 112 Selectivity for Dopamine D₁and Serotonin 5-HT_2AReceptors: A PET Study in Healthy Human Subjects

[¹¹C]NNC 112 Selectivity for Dopamine D₁and Serotonin 5-HT_2AReceptors: A PET Study in Healthy Human Subjects

Validation of the Octamouse for Simultaneous ¹⁸F-Fallypride Small-Animal PET Recordings from 8 Mice