Imaging serotonin transporters using [123I]ADAM SPECT in a parkinsonian primate model

Ma, Kuo‐Hsing; Huang, Wen‐Sheng; Huang, San-Yuan; Cheng, Cheng‐Yi; Chen, Ching-Yuan; Shen, Lie-Hang; Liu, Jiang-Chuan; Fu, Ying

doi:10.1016/j.apradiso.2008.06.033

Cited by 11 publications

(10 citation statements)

References 28 publications

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“…In a previous study, we demonstrated that lower 4-[ 18 F]ADAM PET binding was associated with reduced SERT immunoreactivity by 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in a rat model [25]. This result was in agreement with the study that reported by [ 123 I]ADAM/SPECT imaging that SERT levels were decreased in monkey brains following 6-OHDA injections into the medial forebrain bundle [26]. Those studies determined that 4-[ 18 F]ADAM PET could be used to detect serotonergic neuron loss or dysfunction of SERTs.…”

Section: Introductionsupporting

confidence: 89%

In vivo long-lasting alterations of central serotonin transporter activity and associated dopamine synthesis after acute repeated administration of methamphetamine

et al. 2019

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Background Methamphetamine (METH)-associated alterations in the striatal dopamine (DA) system or dopamine transport (DAT) have been identified in clinical and preclinical studies with positron emission tomography (PET) imaging but have not been well correlated with in vivo serotonin transporter (SERT) availability due to the lack of appropriate imaging agents to assess SERTs. N,N-dimethyl-2-(2-amino-4-[18F]-fluorophenylthio) benzylamine (4-[18F]-ADAM) has been developed by our group and validated for its high affinity and selectivity for SERTs, allowing the in vivo examination of SERT density, location, and binding function. The aims of this study were to investigate the potential of SERT imaging using 4-[18F]-ADAM PET to estimate the long-lasting effects of METH-induced serotonergic neurotoxicity, and further determine whether a correlative relationship exists between SERT availability/activity and tyrosine hydroxylase (TH) activity in various brain regions due to the long-lasting consequences of METH treatment. Results Male rats received four administrations of METH (5 or 10 mg/kg, s.c.) or saline (1 ml/kg, s.c.) at 1-h intervals. At 30 days post-administration, in vivo SERT availability and activity were measured by 4-[18F]ADAM PET imaging. In contrast to the controls, the uptake of 4-[18F]ADAM in METH-treated mice was significantly reduced in a dose-dependent manner in the midbrain, followed by the hypothalamus, thalamus, striatum, hippocampus, and frontal cortex. The regional effects of METH on TH activity were assessed by quantitative immunohistochemistry and presented as integrated optical density (IOD). A significant decrease in TH immunostaining and IOD ratios was seen in the caudate, putamen, nucleus accumbens, substantia nigra pars compacta, and substantia nigra pars reticulata in the METH-treated rats compared to controls. Conclusion The present results suggested that the long-lasting response to METH decreased the uptake of 4-[18F]-ADAM and varied regionally along with TH immunoreactivity. In addition, 4-[18F]ADAM PET could be used to detect serotonergic neuron loss and to evaluate the severity of serotonergic neurotoxicity of METH.

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Section: Introductionsupporting

confidence: 89%

In vivo long-lasting alterations of central serotonin transporter activity and associated dopamine synthesis after acute repeated administration of methamphetamine

et al. 2019

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“…have suggested that used [ 123 I]-ADAM to demonstrate decreased SERT binding in midbrain of patients with major depression27. In our previous studies, [ 123 I]-ADAM was used to monitor the serotonergic system in brain of non-human primate2829. We also found that MDMA induced neurite damage and neuron death in serotonergic neuron in vitro 30.…”

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confidence: 83%

Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT

Hsing

Liu

Weng

et al. 2016

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3,4-Methylenedioxymethamphetamine (MDMA), a common recreational drug, is known to cause serotonergic neurotoxicity in the brain. Dextromethorphan (DM) is a widely used antitussive reported to exert anti-inflammatory effect in vivo. In this study, we examined the long-term effect of MDMA on the primate serotonergic system and the protective property of DM against MDMA-induced serotonergic abnormality using single photon emission computed tomography (SPECT). Nine monkeys (Macaca cyclopis) were divided into three groups, namely control, MDMA and co-treatment (MDMA/DM). [123I]-ADAM was used as the radioligand for serotonin transporters (SERT) in SPECT scans. SERT levels of the brain were evaluated and presented as the uptake ratios (URs) of [123I]-ADAM in several regions of interest of the brain including midbrain, thalamus and striatum. We found that the URs of [123I]-ADAM were significantly lower in the brains of MDMA than control group, indicating lower brain SERT levels in the MDMA-treated monkeys. This MDMA-induced decrease in brain SERT levels could persist for over four years. However, the loss of brain SERT levels was not observed in co-treatment group. These results suggest that DM may exert a protective effect against MDMA-induced serotonergic toxicity in the brains of the non-human primate.

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“…While considered primarily a disease of dopaminergic neurons, some symptoms of PD may result from loss of non-dopaminergic neurons including serotonergic neurons in the median raphe, noradrenergic neurons in the locus coeruleus, cholinergic neurons in the nucleus basalis, as well as other pigmented and brainstem nuclei (2,6). Recently, in order to better elucidate the various aspects of PD, positron emission tomography (PET) and single photon emission computed tomography (SPECT) have provided powerful noninvasive methods for examining changes in monoaminergic systems and monitoring the progress of disease, as well as the effectiveness of therapies (9,25,29,34).…”

Section: Introductionmentioning

confidence: 99%

PET Imaging of Serotonin Transporters with 4-[¹⁸F]-ADAM in a Parkinsonian Rat Model

et al. 2013

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This study was undertaken to address the effects of fetal mesencephalic tissue transplantation on the serotonin system in a rat model of Parkinson's disease (PD) while also investigating the usefulness of 4-[18 F]-ADAM (a serotonin transporter imaging agent) coupled with micro-PET for imaging serotonin transporters (SERTs). A PD model was induced by unilateral injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle of the nigrostriatal pathway, while cell transplantation was performed via intrastriatal injection of mesencephalic brain tissue dissected from embryonic (E14) rats. The 4-[18 F]-ADAM/micro-PET scanning was performed following both 6-OHDA lesioning and transplantation. Immunohistochemistry (IHC) studies were also performed following the final PET scan, and the results were compared to show a 17-43% decrease in the specific uptake ratio (SUR) and a 23-52% decrease in serotonin transporter immunoreactivity (SERT-ir) within various brain regions on the lesioned side. The number of methamphetamine-induced rotations also decreased significantly at the 4th week postgraft. In addition, striatal SUR and the SERT-ir levels were restored to 77% and 83% 5 weeks postgraft. These results suggest that Parkinson's disease also affects the serotonergic system, while both the dopaminergic and serotonergic systems can be partially restored in a rat model of PD after E14 mesencephalic tissue transplantation. In addition, we have also determined that 4-[ 18 F]-ADAM/micro-PET can be used to detect serotonergic neuron loss, monitor the progress of Parkinson's disease, and oversee the effectiveness of therapy.

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Imaging serotonin transporters using [123I]ADAM SPECT in a parkinsonian primate model

Cited by 11 publications

References 28 publications

In vivo long-lasting alterations of central serotonin transporter activity and associated dopamine synthesis after acute repeated administration of methamphetamine

In vivo long-lasting alterations of central serotonin transporter activity and associated dopamine synthesis after acute repeated administration of methamphetamine

Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT

PET Imaging of Serotonin Transporters with 4-[¹⁸F]-ADAM in a Parkinsonian Rat Model

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Imaging serotonin transporters using [123I]ADAM SPECT in a parkinsonian primate model

Cited by 11 publications

References 28 publications

In vivo long-lasting alterations of central serotonin transporter activity and associated dopamine synthesis after acute repeated administration of methamphetamine

In vivo long-lasting alterations of central serotonin transporter activity and associated dopamine synthesis after acute repeated administration of methamphetamine

Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT

PET Imaging of Serotonin Transporters with 4-[18F]-ADAM in a Parkinsonian Rat Model

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PET Imaging of Serotonin Transporters with 4-[¹⁸F]-ADAM in a Parkinsonian Rat Model