In vitro and in vivo evaluation of the binding of the dopamine D2 receptor agonist11C-(R,S)-5-hydroxy-2-(di-n-propylamino)tetralin in rodents and nonhuman primate

Narayanan, Tanjore K.; Christian, Bradley T.; Shi, Bingzhi; Dunigan, Kelly; Mantil, Joseph

doi:10.1002/(sici)1098-2396(200007)37:1<64::aid-syn7>3.0.co;2-f

Cited by 18 publications

(14 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Like PHNO, 3 H‐PD128907 is likely a D3R preferred radioligand with a high liklihood of binding to D2 high sites as well. Similarly, we have reported 11 C‐5‐OH‐DPAT and 18 F‐5‐OH‐FPPAT, which bind to striatum in vitro and in vivo and are sensitive to Gpp(NH)p and are considered as D2R high binding agents (Mukherjee et al, ; Shi et al, ). The D3R component of these derivatives have yet to be determined.…”

Section: Evidence Of D3 Receptors Using Imaging Methodsmentioning

confidence: 79%

See 1 more Smart Citation

Dopamine D3 receptor binding of¹⁸F-fallypride: Evaluation usingin vitroandin vivoPET imaging studies

Mukherjee

Constantinescu

Hoang

et al. 2015

Synapse

Self Cite

View full text Add to dashboard Cite

Identification of dopamine D3 receptors (D3R) in vivo is important to understand several brain functions related to addiction. The goal of this work was to identify D3R binding of the dopamine D2 receptor (D2R)/D3R imaging agent, 18F-fallypride. Brain slices from male Sprague-Dawley rats (n=6) and New Zealand White rabbits (n=6) were incubated with 18F-fallypride and D3R selective agonist (R)-7-OH-DPAT (98-fold D3R selective). Rat slices were also treated with BP 897 (68-fold D3R selective partial agonist) and NGB 2904 (56-fold D3R selective antagonist). In vivo rat studies (n=6) were done on Inveon PET using 18–37 MBq 18F-fallypride and drug-induced displacement by (R)-7-OH-DPAT, BP 897 and NGB 2904. PET/CT imaging of wild type (WT, n=2) and D2R knock-out (KO, n=2) mice were carried out with 18F-fallypride. (R)-7-OH-DPAT displaced binding of 18F-fallypride, both in vitro and in vivo. In vitro, at 10 nM (R)-7-OH-DPAT, 18F-fallypride binding in the rat ventral striatum (VST) and dorsal striatum (DST) and rabbit nucleus accumbens were reduced by ~10–15%. At 10 µM (R)-7-OH-DPAT all regions in rat and rabbit were reduced by ≥85%. In vivo reductions for DST and VST before and after (R)-7-OH-DPAT were: low-dose (0.015mg/kg) DST −22%, VST −29%; high-dose (1.88 mg/kg) DST −58%, VST −77%, suggesting D3R/D2R displacement. BP 897 and NGB 2904 competed with 18F-fallypride in vitro, but unlike BP 897, NGB2904 did not displace 18F-fallypride in vivo. The D2R KO mice lacked 18F-fallypride binding in the DST. In summary, our findings suggest that up to 20% of 18F-fallypride may be bound to D3R sites in vivo.

show abstract

Section: Evidence Of D3 Receptors Using Imaging Methodsmentioning

confidence: 79%

“…The binding of 7‐OH‐DPAT to the uncoupled D2R low‐affinity (D2 low ) sites was found to be too low (Gonzalez and Sibley, ). We have previously shown that 11 C‐5‐OH‐DPAT is able to penetrate the rodent and nonhuman primate brain (Mukherjee et al, ). Uptake of 11 C‐5‐OH‐DPAT in the rat brain was ∼1% of the injected dose.…”

Section: Discussionmentioning

confidence: 97%

Dopamine D3 receptor binding of¹⁸F-fallypride: Evaluation usingin vitroandin vivoPET imaging studies

Mukherjee

Constantinescu

Hoang

et al. 2015

Synapse

Self Cite

View full text Add to dashboard Cite

show abstract

“…Several agonists have been pursued for in vivo imaging. Aminotetralins, 11 C‐5‐OH‐DPAT, 11 C‐PPHT, 11 C‐ZYY339, and 18 F‐5‐OH‐FPPAT have been reported by us for successful PET imaging of dopamine receptors (Mukherjee et al, ; Shi et al, ). Depending on the position of the phenolic hydroxyl (5‐ or 7), the aminotetralins can exhibit higher affinity for D2 while maintaining a similar affinity for D3 receptors (Figure , 1 ).…”

Section: Introductionmentioning

confidence: 99%

PET radiotracer development for imaging high‐affinity state of dopamine D2 and D3 receptors: Binding studies of fluorine‐18 labeled aminotetralins in rodents

Majji

Kaur

Constantinescu

et al. 2016

Synapse

Self Cite

View full text Add to dashboard Cite

Imaging the high-affinity, functional state (HA) of dopamine D2 and D3 receptors has been pursued in PET imaging studies of various brain functions. We report further evaluation of 18F-5-OH-FPPAT, and the newer 18F-5-OH-FHXPAT and 18F-7-OH-FHXPAT. Syntheses of 18F-5-OH-FHXPAT and 18F-7-OH-FHXPAT were improved by modifications of our previously reported procedures. Brain slices and brain homogenates from male Sprague-Dawley rats were used with the 3 radiotracers (74–111 kBq/cc). Competition with dopamine (1–100 nM) and Gpp(NH)p (10–50 μM) were carried out to demonstrate binding to dopamine D2 and D3 HA-states and binding kinetics of 18F-5-OH-FPPAT measured. Ex vivo brain slice autoradiography was carried out on rats administered with 18F-5-OH-FHXPAT to ascertain HA-state binding. PET/CT imaging in rats and wild type (WT) and D2 knock-out mice were carried out using 18F-7-OH-FHXPAT (2–37 MBq). Striatum was clearly visualized by the three radiotracers in brain slices and dopamine displaced more than 80% of binding, with dissociation rate in homogenates of 2.2 × 10−2 min−1 for 18F-5-OH-FPPAT. Treatment with Gpp(NH)p significantly reduced 50–80% striatal binding with faster dissociation rates (5.0 × 10−2 min−1), suggesting HA-state binding of 18F-5-OH-FPPAT and 18F-5-OH-FHXPAT. Striatal binding of 18F-5-OH-FHXPAT in ex vivo brain slices were sensitive to Gpp(NH)p, suggesting HA-state binding in vivo. PET binding ratios of 18F-7-OH-FHXPAT in rat brain were ventral striatum/cerebellum=2.09 and dorsal striatum/cerebellum=1.65; similar binding ratios were found in the D2 WT mice. These results suggest that in vivo PET measures of agonists in the brain at least in part reflect binding to the membrane-bound HA-state of the dopamine receptor.

show abstract

“…So far, all D 2/3 radioligands used in human PET or SPECT studies are radio-labelled antagonists, which do not differentiate between D 2 high and D 2 low . Several research groups have recently reported on development and experimental use of newly developed D 2/3 agonist radioligands (Zijlstra et al, 1993a, b;Shi et al, 1999Shi et al, , 2004Hwang et al, 2000;Mukherjee et al, 2000Mukherjee et al, , 2004Finnema et al, 2005;Narendran et al, 2004). Similar to dopamine, D 2/3 agonist radioligands are expected to bind mainly to D 2 high .…”

Section: Introductionmentioning

confidence: 99%

First Human Evidence of d-Amphetamine Induced Displacement of a D2/3 Agonist Radioligand: A [11C]-(+)-PHNO Positron Emission Tomography Study

Willeit

Ginovart

Graff

et al. 2007

Neuropsychopharmacol

100

View full text Add to dashboard Cite

Imaging the competition between D(2/3) radioligands and endogenous dopamine is so far the only way to measure dopamine release in the living human brain. The dopamine D(2) receptor exists in a high (D(2)(high)) and a low-affinity state for dopamine. Under physiological conditions, dopamine is expected to bind to D(2)(high) only. [(11)C]-(+)-4-propyl-9-hydroxynaphthoxazine ((+)-PHNO) is the first D(2/3) agonist radioligand for positron emission tomography (PET) imaging in humans. Since [(11)C]-(+)-PHNO is expected to bind preferentially to D(2)(high), it should be particularly vulnerable to competition with endogenous dopamine. Nine healthy subjects participated in two PET scans, one after administration of d-amphetamine and one after placebo. [(11)C]-(+)-PHNO PET test re-test variability was determined in 11 healthy subjects. Binding potentials (BPs) were calculated for caudate, putamen, ventral striatum, and globus pallidus. d-Amphetamine led to a significant decrease of [(11)C]-(+)-PHNO BPs in caudate (-13.2%), putamen (-20.8%), and ventral striatum (-24.9%), but not in globus pallidus (-6.5%). d-Amphetamine-induced displacement correlated with serum d-amphetamine levels in all regions but caudate. This is the first report on competition between endogenous dopamine and a D(2/3) agonist radioligand in humans. [(11)C]-(+)-PHNO PET might be a superior measure for release of endogenous dopamine than PET employing conventional D(2/3) antagonist radioligands.

show abstract

In vitro and in vivo evaluation of the binding of the dopamine D2 receptor agonist11C-(R,S)-5-hydroxy-2-(di-n-propylamino)tetralin in rodents and nonhuman primate

Cited by 18 publications

References 16 publications

Dopamine D3 receptor binding of¹⁸F-fallypride: Evaluation usingin vitroandin vivoPET imaging studies

Dopamine D3 receptor binding of¹⁸F-fallypride: Evaluation usingin vitroandin vivoPET imaging studies

PET radiotracer development for imaging high‐affinity state of dopamine D2 and D3 receptors: Binding studies of fluorine‐18 labeled aminotetralins in rodents

First Human Evidence of d-Amphetamine Induced Displacement of a D2/3 Agonist Radioligand: A [11C]-(+)-PHNO Positron Emission Tomography Study

Contact Info

Product

Resources

About

In vitro and in vivo evaluation of the binding of the dopamine D2 receptor agonist11C-(R,S)-5-hydroxy-2-(di-n-propylamino)tetralin in rodents and nonhuman primate

Cited by 18 publications

References 16 publications

Dopamine D3 receptor binding of18F-fallypride: Evaluation usingin vitroandin vivoPET imaging studies

Dopamine D3 receptor binding of18F-fallypride: Evaluation usingin vitroandin vivoPET imaging studies

PET radiotracer development for imaging high‐affinity state of dopamine D2 and D3 receptors: Binding studies of fluorine‐18 labeled aminotetralins in rodents

First Human Evidence of d-Amphetamine Induced Displacement of a D2/3 Agonist Radioligand: A [11C]-(+)-PHNO Positron Emission Tomography Study

Contact Info

Product

Resources

About

Dopamine D3 receptor binding of¹⁸F-fallypride: Evaluation usingin vitroandin vivoPET imaging studies

Dopamine D3 receptor binding of¹⁸F-fallypride: Evaluation usingin vitroandin vivoPET imaging studies