scholarly journals Evaluation of dopamine D3 receptor occupancy by blonanserin using [11C]-(+)-PHNO in schizophrenia patients

2020 ◽  
Author(s):  
Takeshi Sakayori ◽  
Amane Tateno ◽  
Ryosuke Arakawa ◽  
Woo-chan Kim ◽  
Yoshiro Okubo
Keyword(s):  
Substantia Nigra ◽  
Globus Pallidus ◽  
Healthy Subjects ◽  
Receptor Occupancy ◽  
Binding Potential ◽  
Positron Emission ◽  
Dopamine D3 ◽  
Continued Use ◽  
Pet Scans ◽  
Average Occupancy

Abstract Rationale Unlike other antipsychotics, our previous positron emission tomography (PET) study demonstrated that a single dose of blonanserin occupied dopamine D3 as well as dopamine D2 receptors in healthy subjects. However, there has been no study concerning the continued use of blonanserin. Objectives We examined D2 and D3 receptor occupancies in patients with schizophrenia who had been treated with blonanserin. Methods Thirteen patients with schizophrenia participated. PET examinations were performed on patients treated with clinical dosage of blonanserin or olanzapine alone. A crossover design was used in which seven patients switched drugs after the first scan, and PET examinations were conducted again. D2 and D3 receptor occupancies were evaluated by [11C]-(+)-PHNO. We used nondisplaceable binding potential (BPND) of 6 healthy subjects which we previously reported as baseline. To consider the effect of upregulation of D3 receptor by continued use of antipsychotics, D3 receptor occupancy by blonanserin in seven subjects who completed 2 PET scans were re-analyzed by using BPND of olanzapine condition as baseline. Results Average occupancy by olanzapine (10.8 ± 6.0 mg/day) was as follows: caudate 32.8 ± 18.3%, putamen 26.3 ± 18.2%, globus pallidus − 33.7 ± 34.9%, substantia nigra − 112.8 ± 90.7%. Average occupancy by blonanserin (12.8 ± 5.6 mg/day) was as follows: caudate 61.0 ± 8.3%, putamen 55.5 ± 9.5%, globus pallidus 48.9 ± 12.4%, substantia nigra 34.0 ± 20.6%. EC50 was 0.30 ng/mL for D2 receptor for caudate and putamen (df = 19, p < 0.0001) and 0.70 ng/mL for D3 receptor for globus pallidus and substantia nigra (df = 19, p < 0.0001). EC50 for D3 receptor of blonanserin changed to 0.22 ng/mL (df = 13, p = 0.0041) when we used BPND of olanzapine condition as baseline. Conclusions Our study confirmed that blonanserin occupied both D2 and D3 receptors in patients with schizophrenia.

scholarly journals The applicability of SRTM in [18F]fallypride PET investigations: Impact of scan durations

2011 ◽  
Vol 31 (9) ◽  
pp. 1958-1966 ◽  
Author(s):  
Ingo Vernaleken ◽  
Lisa Peters ◽  
Mardjan Raptis ◽  
Robert Lin ◽  
Hans-Georg Buchholz ◽  
...  
Keyword(s):  
Temporal Cortex ◽  
Receptor Occupancy ◽  
Binding Potential ◽  
Reference Tissue ◽  
Scan Time ◽  
Positron Emission ◽  
Simplified Reference Tissue Model ◽  
Pet Scans ◽  
Drug Free ◽  
Time Point

The high-affinity radioligand [18F]fallypride (FP) is frequently used for quantification of striatal/extrastriatal D2/3 receptors and the receptor occupancies of antipsychotics (APs). Its 110 minutes half-life allows long scan durations. However, the optimum scan duration is a matter of debate. This investigation focuses on scan-duration-related effects on simplified reference tissue model (SRTM) results and the time point of transient equilibrium in a large sample of dynamic FP positron emission tomography (PET) scans. Fifty drug-free and 50 AP-treated subjects underwent FP-PET scans (180 minutes scan duration). The binding potential ( BPND) of the putamen, thalamus, and temporal cortex were calculated using the SRTM and the transient equilibrium model. Furthermore, receptor occupancies were calculated for AP-treated patients. Transient equilibrium in the unblocked putamen occurred after 121 ± 29.6 minutes. The transient equilibrium occurred much earlier in the extrastriatal regions or under AP treatment. Stepwise scan shortening caused BPND under-estimations of 0.58% for the first 10-minute reduction (putamen, SRTM), finally reaching 5.76% after 1 hour scan-time reduction. We observed preferential extrastriatal AP binding irrespective of the analytical method. [18F]fallypride scan durations of 180 minutes reliably reach equilibrium even in D2/3-receptor-rich regions. Moderate reductions in FP scan durations only caused small changes to SRTM results even in receptor-rich regions. Apparently, the D2/3 receptor occupancy results of APs, especially preferential extrastriatal binding observations, are not relevantly biased by inappropriate scan durations.

scholarly journals Determination of receptor occupancy in the presence of mass dose: [11C]GSK189254 PET imaging of histamine H3 receptor occupancy by PF-03654746

2016 ◽  
Vol 37 (3) ◽  
pp. 1095-1107 ◽  
Author(s):  
Jean-Dominique Gallezot ◽  
Beata Planeta ◽  
Nabeel Nabulsi ◽  
Donna Palumbo ◽  
Xiaoxi Li ◽  
...  
Keyword(s):  
Binding Sites ◽  
Human Subjects ◽  
Receptor Occupancy ◽  
Healthy Human ◽  
Positron Emission ◽  
Relationship Of ◽  
The Relationship ◽  
Pet Scans

Measurements of drug occupancies using positron emission tomography (PET) can be biased if the radioligand concentration exceeds “tracer” levels. Negative bias would also arise in successive PET scans if clearance of the radioligand is slow, resulting in a carryover effect. We developed a method to (1) estimate the in vivo dissociation constant Kd of a radioligand from PET studies displaying a non-tracer carryover (NTCO) effect and (2) correct the NTCO bias in occupancy studies taking into account the plasma concentration of the radioligand and its in vivo Kd. This method was applied in a study of healthy human subjects with the histamine H3 receptor radioligand [11C]GSK189254 to measure the PK-occupancy relationship of the H3 antagonist PF-03654746. From three test/retest studies, [11C]GSK189254 Kd was estimated to be 9.5 ± 5.9 pM. Oral administration of 0.1 to 4 mg of PF-03654746 resulted in occupancy estimates of 71%–97% and 30%–93% at 3 and 24 h post-drug, respectively. NTCO correction adjusted the occupancy estimates by 0%–15%. Analysis of the relationship between corrected occupancies and PF-03654746 plasma levels indicated that PF-03654746 can fully occupy H3 binding sites ( ROmax = 100%), and its IC50 was estimated to be 0.144 ± 0.010 ng/mL. The uncorrected IC50 was 26% higher.

In Vivo PET Measurements with [11C]PE2I to Evaluate Fetal Mesencephalic Transplantations to Unilateral 6-OHDA-Lesioned Rats

2005 ◽  
Vol 14 (9) ◽  
pp. 655-663 ◽  
Author(s):  
Motoki Inaji ◽  
Takahito Yoshizaki ◽  
Takashi Okauchi ◽  
Jun Maeda ◽  
Yuji Nagai ◽  
...  
Keyword(s):  
Dopamine Transporter ◽  
High Performance ◽  
Emission Tomography ◽  
Binding Potential ◽  
In Vitro Autoradiography ◽  
Positron Emission ◽  
Pet Scans ◽  
Mesencephalic Cells

Positron emission tomography (PET) is a useful tool to assess and visualize neurotransmissions in vivo. In this study, we performed repeated PET scans with [11C]PE2I, a tracer of the dopamine transporter, to evaluate the alteration of the expression of dopamine (DA) transmission component after a fetal mesencephalic transplantation. The fetal mesencephalic cells were transplanted into the striatum of unilateral 6-OHDA-lesioned rats. PET scans with [11C]PE2I were performed to evaluate the DA transporter before and 2 and 4 weeks after the transplantation. Rotation behavior tests, in vitro autoradiography, measurements of DA contents in the striatum by high-performance liquid chromatography (HPLC), and tyrosine hydroxylase (TH) immuno-histological examinations were performed at the same time points and examined for their relationship to changes in the dopamine transporter. The number of ipsilateral rotations induced by methamphetamine injections decreased. DA contents in the striatum measured with HPLC significantly increased. In the PET study, the binding potential of [11C]PE2I increased at 4 weeks. The results of the in vitro autoradiography study corresponded with those of the PET study. The degrees of the change in the binding potentials correlated with those of the numbers of rotations in the behavioral study and the DA contents in the striatum. In the histological examination, TH-positive cells with axons were observed at 2 and 4 weeks after the transplantation. As the dopamine transporter exists only in the axon terminal of DA neurons, these results suggested that PET measurements of [11C]PE2I binding indicated not only survival, but maturity and functioning of the transplanted cells. Repeated PET measurements of DA transporters are a useful tool in assessing the effectiveness of neural transplantations.

scholarly journals The influence of conditioned stimuli on [11C]-(+)-PHNO PET binding in tobacco smokers after a one week abstinence

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Patricia Di Ciano ◽  
Harriet de Wit ◽  
Esmaeil Mansouri ◽  
Sylvain Houle ◽  
Isabelle Boileau ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Preliminary Finding ◽  
Regions Of Interest ◽  
Ventral Pallidum ◽  
Binding Potential ◽  
Brain Areas ◽  
Positron Emission ◽  
Smoking Cues ◽  
Pet Scans ◽  
Larger Sample

AbstractStimuli previously paired with drugs of dependence can produce cravings that are associated with increased dopamine (DA) levels in limbic and striatal brain areas. Positron Emission Tomography (PET) imaging with [11C]-(+)-PHNO allows for a sensitive measurement of changes in DA levels. The purpose of the present study was to investigate changes in DA levels, measured with PET imaging with [11C]-(+)-PHNO, in regions of interest in smokers who had maintained abstinence for 7–10 days. Participants (N = 10) underwent two PET scans on separate days, during which they viewed either smoking-related or neutral images, in counterbalanced order. Craving was measured with the 12-item Tobacco Craving Questionnaire (TCQ) and the Questionnaire on Smoking Urges-Brief (QSU-B). Compared to neutral cues, smoking cues did not increase craving. There were no changes in [11C]-(+)-PHNO binding in the cue condition compared to the neutral condition for most regions of interest (ventral pallidum, globus pallidus, limbic striatum, associative striatum, sensorimotor striatum). However, binding potential in the substantia nigra was greater in the smoking-cue condition, indicating decreased synaptic dopamine. There is a potential change of DA level occurring in midbrain following the presentation of smoking-related cues. However, this preliminary finding would need to be validated with a larger sample.

A PET study with [11C]AZ10419369 to determine brain 5-HT1B receptor occupancy of zolmitriptan in healthy male volunteers

Cephalalgia ◽  
2013 ◽  
Vol 33 (10) ◽  
pp. 853-860 ◽  
Author(s):  
Katarina Varnäs ◽  
Aurelija Jučaitė ◽  
Dennis J McCarthy ◽  
Per Stenkrona ◽  
Magdalena Nord ◽  
...  
Keyword(s):  
Human Subjects ◽  
Negative Relationship ◽  
Receptor Occupancy ◽  
G Protein Coupled Receptors ◽  
Binding Potential ◽  
Healthy Male ◽  
Orodispersible Tablets ◽  
Positron Emission ◽  
Significant Negative Relationship ◽  
G Protein Coupled

Aim To investigate the occupancy at brain 5-hydroxytryptamine (5-HT) 1B receptors in human subjects after administration of the antimigraine drug zolmitriptan. Methods Positron emission tomography (PET) studies were undertaken using the radioligand [11C]AZ10419369 in eight control subjects at baseline and after administration of zolmitriptan orodispersible tablets. The subjects were examined after two consecutive administrations of 10 mg zolmitriptan, approximately 1 week apart. Two of the subjects were subsequently examined after administration of 5 mg zolmitriptan. One week after the last administration of zolmitriptan five of the subjects underwent additional PET measurements without drug pretreatment. Results After administration of 10 mg zolmitriptan, mean receptor occupancy was 4–5%. No consistent changes in 5-HT1B receptor binding were observed for subjects who received 5 mg zolmitriptan. There was a statistically significant negative relationship between binding potential ( BPND) and plasma concentration of zolmitriptan and the active metabolite 183C91, respectively. All of the five subjects who were examined 1 week after dosing with zolmitriptan showed higher BPND post drug administration compared with baseline. Conclusion This is the first demonstration of CNS 5-HT1B receptor occupancy of a triptan. The findings are consistent with the low receptor occupancy previously reported in PET studies with agonists at other G protein coupled receptors.

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