Acute effects of three club drugs on the striatum of rats: Evaluation by quantitative autoradiography with [18F]FDOPA

Fang, Cheng; Chen, Hong Wen; Wang, Wei Hsun; Liu, Ren Shen; Hwang, Jeng Jong

doi:10.1016/j.apradiso.2013.03.091

Cited by 6 publications

(8 citation statements)

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“…Virtually all of the selective binding, as indicated by the ratios of striatum/cerebellum, can be blocked by posttreatments with recreational drugs, ketamine, cocaine, and methamphetamine. We also observed the dose-dependent effect of acute administration of these drugs by using PET and QWBAR, which was in a good agreement with previous studies [18, 26, 27]. The inhibition effects of the [ 18 F]FDOPA accumulation in striatum or tissues were varied.…”

Section: Discussionsupporting

confidence: 91%

“…In comparison with previous reports of [ 18 F]FDOPA [15, 18], our results provided more information on tissue distribution either by tissue dissection or QWBAR and also the distribution in later time points. In the current study, despite the good SBR in striatum and cerebellum of the mice, the hepatobiliary clearance followed two-phase exponential dissociation kinetics with a fast initial phase (0–15 minutes) and a very slow subsequent phase (30–240 minutes).…”

Section: Discussionsupporting

confidence: 59%

“…The effects of recreational drug such as ketamine, cocaine, and methamphetamine on dopamine neurons have been reported in the brains in rodent [18], nonhuman primate models [19], or human studies [20]; however, there is little investigation for the functional roles of peripheral dopamine or the side effects of these drugs in peripheral organs. The goal of this study was to evaluate the alteration of presynaptic dopaminergic terminal function after acute administration of ketamine by in vivo [ 18 F]FDOPA PET imaging and quantitative whole-body autoradiography (QWBAR).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Inhibitory Effect of Recreational Drugs on Dopaminergic Terminal Neuron by PET and Whole-Body Autoradiography

Yeh

Lin

Kong

et al. 2014

BioMed Research International

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There is little investigation for the functional roles of peripheral dopamine. [18F]FDOPA has been used in cancer imaging (i.e., neuroendocrine and tumors pancreatic tumors) and neuroimaging (i.e., Parkinson's disease and Huntington's disease). Here, we accessed side effects of recreational drugs such as ketamine, cocaine, and methamphetamine on dopamine neurons in peripheral organs by using positron emission tomography (PET) imaging and quantitative whole-body autoradiography (QWBAR) with [18F]FDOPA. The images were applied for the measurement of specific binding ratios (SBRs) of striatum with the cerebellum as the reference region. Clear striatal [18F]FDOPA-derived radioactivity was observed. Moderate level of radiotracer accumulation was presented in the mucosal layers of the stomach and small intestine. The medulla layers of kidney had higher radioactivity than that of the cortex. Blocking images markedly eliminated the specific binding of [18F]FDOPA in the striatum and in peripheral organs such as stomachs, intestines, and kidney. Ketamine showed the highest inhibitory effect on striatal [18F]FDOPA-derived radioactivity followed by cocaine and methamphetamine. The current results demonstrated a useful crossing-validating tool that enhances the capability of [18F]FDOPA for further investigations of the alteration of dopaminergic neurons in the brain disorder or cancer diseases in peripheral tissues.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

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Evaluation of Inhibitory Effect of Recreational Drugs on Dopaminergic Terminal Neuron by PET and Whole-Body Autoradiography

Yeh

Lin

Kong

et al. 2014

BioMed Research International

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“…As these studies were all done in chronic users it is not known if acute use results in reduced dopamine synthesis capacity in humans but there is some evidence from two animal studies that acute use results in dose-dependent decreases in presynaptic dopamine activity with increasing cocaine concentrations (Fang et al, 2013; Yeh et al, 2014). However, these studies used quantitative autoradiography techniques to measure specific binding ratios at a fixed time (2hrs) after [ 18 F]-FDOPA administration to determine tracer uptake.…”

Section: Introductionmentioning

confidence: 99%

Single cocaine exposure does not alter striatal pre‐synaptic dopamine function in mice: an [¹⁸F]‐FDOPA PET study

Bonsall

Kokkinou

Veronese

et al. 2017

Journal of Neurochemistry

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Cocaine is a recreational drug of abuse that binds to the dopamine transporter (DAT), preventing reuptake of dopamine into presynaptic terminals. The increased presence of synaptic dopamine results in stimulation of both pre- and postsynaptic dopamine receptors, considered an important mechanism by which cocaine elicits its reinforcing properties. However, the effects of acute cocaine administration on presynaptic dopamine function remain unclear. Non-invasive imaging techniques such as positron emission tomography (PET) have revealed impaired presynaptic dopamine function in chronic cocaine users. Similar impairments have been seen in animal studies, with microdialysis experiments indicating decreased basal dopamine release. Here we use μ-PET imaging techniques in mice to measure dopamine synthesis capacity and determine the effect of acute cocaine administration of presynaptic dopamine function. We show that a dose of 20mg/kg cocaine is sufficient to elicit hyperlocomotor activity, peaking 15-20 min post treatment (p<0.001). However, dopamine synthesis capacity in the striatum was not significantly altered by acute cocaine treatment (KiCer: 0.0097 min-1 vs. 0.0112 min-1 in vehicle controls, p>0.05). Furthermore, expression levels of two key enzymes related to dopamine synthesis, tyrosine hydroxylase and aromatic l-amino acid decarboxylase, within the striatum of scanned mice were not significantly affected by acute cocaine pre-treatment (p>0.05). Our findings suggest that while the regulation of dopamine synthesis and release in the striatum have been shown to change with chronic cocaine use, leading to a reduced basal tone, these adaptations to presynaptic dopaminergic neurons are not initiated following a single exposure to the drug.

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“…Autoradiography is a longstanding method for evaluating the distribution of target proteins using radiolabeled ligands ex vivo. The main uses of autoradiography have been the study of changes in neurotransmitter receptors in brain tissue (13)(14)(15) and the study of absorption, distribution, metabolism, and excretion (16,17).…”

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confidence: 99%

Dual-Isotope Cryoimaging Quantitative Autoradiography: Investigating Antibody–Drug Conjugate Distribution and Payload Delivery Through Imaging

et al. 2018

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In vitro properties of antibody-drug conjugates (ADCs) such as binding, internalization, and cytotoxicity are often well characterized before in vivo studies. Interpretation of in vivo studies might be significantly enhanced by molecular imaging tools. We present here a dual-isotope cryoimaging quantitative autoradiography (CIQA) methodology combined with advanced 3-dimensional imaging and analysis allowing for the simultaneous study of both antibody and payload distribution in tissues of interest in a preclinical setting. TAK-264, an investigational ADC targeting anti-guanylyl cyclase C (GCC), was synthesized using tritiated monomethyl auristatin E. The tritiated ADC was then conjugated to diethylenetriaminepentaacetic acid, labeled withIn, and evaluated in vivo in animals bearing GCC-positive and GCC-negative tumors. CIQA revealed the time course of drug release from ADC and its distribution into various tumor regions that are less accessible to the antibody. For GCC-positive tumors, a representative section obtained 96 h after tracer injection showed only 0.8% of the voxels to have colocalized signal, versus over 15% of the voxels for a GCC-negative tumor section, suggesting successful and specific cleaving of the toxin in the GCC-positive lesions. The combination of a veteran established autoradiography technology with advanced image analysis methodologies affords an experimental tool that can support detailed characterization of ADC tumor penetration and pharmacokinetics.

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Acute effects of three club drugs on the striatum of rats: Evaluation by quantitative autoradiography with [18F]FDOPA

Cited by 6 publications

References 53 publications

Evaluation of Inhibitory Effect of Recreational Drugs on Dopaminergic Terminal Neuron by PET and Whole-Body Autoradiography

Evaluation of Inhibitory Effect of Recreational Drugs on Dopaminergic Terminal Neuron by PET and Whole-Body Autoradiography

Single cocaine exposure does not alter striatal pre‐synaptic dopamine function in mice: an [¹⁸F]‐FDOPA PET study

Dual-Isotope Cryoimaging Quantitative Autoradiography: Investigating Antibody–Drug Conjugate Distribution and Payload Delivery Through Imaging

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Acute effects of three club drugs on the striatum of rats: Evaluation by quantitative autoradiography with [18F]FDOPA

Cited by 6 publications

References 53 publications

Evaluation of Inhibitory Effect of Recreational Drugs on Dopaminergic Terminal Neuron by PET and Whole-Body Autoradiography

Evaluation of Inhibitory Effect of Recreational Drugs on Dopaminergic Terminal Neuron by PET and Whole-Body Autoradiography

Single cocaine exposure does not alter striatal pre‐synaptic dopamine function in mice: an [18F]‐FDOPA PET study

Dual-Isotope Cryoimaging Quantitative Autoradiography: Investigating Antibody–Drug Conjugate Distribution and Payload Delivery Through Imaging

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Single cocaine exposure does not alter striatal pre‐synaptic dopamine function in mice: an [¹⁸F]‐FDOPA PET study