Altered dopaminergic function and negative symptoms in drug-free patients with schizophrenia

1997 ◽  
Vol 171 (6) ◽  
pp. 574-577 ◽  
Author(s):  
Michael B. Knable ◽  
Michael F. Egan ◽  
Andreas Heinz ◽  
Julia Gorey ◽  
Kan Sam Lee ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Endogenous Dopamine ◽  
Significant Difference ◽  
Drug Free ◽  
Neuroleptic Withdrawal ◽  
Scanning Session

BackgroundPrevious in vivo studies of schizophrenia with dopamine D2 receptor radioligands have yielded contradictory results. No prior study has used multiple scans to examine within-subject clinical change.MethodTwenty-one patients were studied with [1231]-iodobenzamide single photon emission computed tomography about two weeks after neuroleptic withdrawal. Thirteen of the 21 completed a second scan about four weeks after neuroleptic withdrawal. Sixteen controls were scanned for comparison.ResultsThere was no significant difference between groups in [1231]-iodobenzamide uptake at either scanning session. No significant correlations with demographic variables (age, illness duration, drug-free period), or clinical ratings (positive and negative symptoms, movement disorder) were observed at either scanning session. There was a significant correlation between change in [1231]-iodobenzamide uptake and change in negative symptom ratings for the subjects who underwent two scans (r=0.72, P < 0.05)ConclusionsWorsening of negative symptoms may be associated with increased availability of striatal D2 receptors, perhaps because of decreased concentrations of endogenous dopamine.

scholarly journals Sorbitol as a Polar Pharmacological Modifier to Enhance the Hydrophilicity of 99mTc-Tricarbonyl-Based Radiopharmaceuticals

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2680
Author(s):  
Carolina Giammei ◽  
Theresa Balber ◽  
Katarina Benčurová ◽  
Jens Cardinale ◽  
Neydher Berroterán-Infante ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
General Applicability ◽  
Cell Internalization ◽  
Significant Difference ◽  
Pharmacokinetic Properties

The organometallic technetium-99m tricarbonyl core, [99mTc][Tc(CO)3(H2O)3]+, is a versatile precursor for the development of radiotracers for single photon emission computed tomography (SPECT). A drawback of the 99mTc-tricarbonyl core is its lipophilicity, which can influence the pharmacokinetic properties of the SPECT imaging probe. Addition of polar pharmacological modifiers to 99mTc-tricarbonyl conjugates holds the promise to counteract this effect and provide tumor-targeting radiopharmaceuticals with improved hydrophilicities, e.g., resulting in a favorable fast renal excretion in vivo. We applied the “Click-to-Chelate” strategy for the assembly of a novel 99mTc-tricarbonyl labeled conjugate made of the tumor-targeting, modified bombesin binding sequence [Nle14]BBN(7–14) and the carbohydrate sorbitol as a polar modifier. The 99mTc-radiopeptide was evaluated in vitro with PC-3 cells and in Fox-1nu mice bearing PC-3 xenografts including a direct comparison with a reference conjugate lacking the sorbitol moiety. The glycated 99mTc-tricarbonyl peptide conjugate exhibited an increased hydrophilicity as well as a retained affinity toward the Gastrin releasing peptide receptor and cell internalization properties. However, there was no significant difference in vivo in terms of pharmacokinetic properties. In particular, the rate and route of excretion was unaltered in comparison to the more lipophilic reference compound. This could be attributed to the intrinsic properties of the peptide and/or its metabolites. We report a novel glycated (sorbitol-containing) alkyne substrate for the “Click-to-Chelate” methodology, which is potentially of general applicability for the development of 99mTc-tricarbonyl based radiotracers displaying an enhanced hydrophilicity.

Correlation between in vitro and in vivo Data of Radiolabeled Peptide for Tumor Targeting

2019 ◽  
Vol 19 (12) ◽  
pp. 950-960
Author(s):  
Soghra Farzipour ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Tumor Targeting ◽  
Single Photon ◽  
Specific Binding ◽  
Specific Interaction ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Mixed Effect ◽  
Radiolabeled Peptides

Tumor-targeting peptides have been generally developed for the overexpression of tumor specific receptors in cancer cells. The use of specific radiolabeled peptide allows tumor visualization by single photon emission computed tomography (SPECT) and positron emission tomography (PET) tools. The high affinity and specific binding of radiolabeled peptide are focusing on tumoral receptors. The character of the peptide itself, in particular, its complex molecular structure and behaviors influence on its specific interaction with receptors which are overexpressed in tumor. This review summarizes various strategies which are applied for the expansion of radiolabeled peptides for tumor targeting based on in vitro and in vivo specific tumor data and then their data were compared to find any correlation between these experiments. With a careful look at previous studies, it can be found that in vitro unblock-block ratio was unable to correlate the tumor to muscle ratio and the success of radiolabeled peptide for in vivo tumor targeting. The introduction of modifiers’ approaches, nature of peptides, and type of chelators and co-ligands have mixed effect on the in vitro and in vivo specificity of radiolabeled peptides.

scholarly journals Dopamine D2/3 Receptor Availabilities and Evoked Dopamine Release in Striatum Differentially Predict Impulsivity and Novelty Preference in Roman High- and Low-Avoidance Rats

2020 ◽  
Author(s):  
Lidia Bellés ◽  
Andrea Dimiziani ◽  
Stergios Tsartsalis ◽  
Philippe Millet ◽  
François R Herrmann ◽  
...  
Keyword(s):  
Ventral Striatum ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Dorsal Striatum ◽  
Reaction Time Task ◽  
Emission Computed Tomography ◽  
Novelty Preference ◽  
Da Release

Abstract Background Impulsivity and novelty preference are both associated with an increased propensity to develop addiction-like behaviors, but their relationship and respective underlying dopamine (DA) underpinnings are not fully elucidated. Methods We evaluated a large cohort (n = 49) of Roman high- and low-avoidance rats using single photon emission computed tomography to concurrently measure in vivo striatal D2/3 receptor (D2/3R) availability and amphetamine (AMPH)-induced DA release in relation to impulsivity and novelty preference using a within-subject design. To further examine the DA-dependent processes related to these traits, midbrain D2/3-autoreceptor levels were measured using ex vivo autoradiography in the same animals. Results We replicated a robust inverse relationship between impulsivity, as measured with the 5-choice serial reaction time task, and D2/3R availability in ventral striatum and extended this relationship to D2/3R levels measured in dorsal striatum. Novelty preference was positively related to impulsivity and showed inverse associations with D2/3R availability in dorsal striatum and ventral striatum. A high magnitude of AMPH-induced DA release in striatum predicted both impulsivity and novelty preference, perhaps owing to the diminished midbrain D2/3-autoreceptor availability measured in high-impulsive/novelty-preferring Roman high-avoidance animals that may amplify AMPH effect on DA transmission. Mediation analyses revealed that while D2/3R availability and AMPH-induced DA release in striatum are both significant predictors of impulsivity, the effect of striatal D2/3R availability on novelty preference is fully mediated by evoked striatal DA release. Conclusions Impulsivity and novelty preference are related but mediated by overlapping, yet dissociable, DA-dependent mechanisms in striatum that may interact to promote the emergence of an addiction-prone phenotype.

scholarly journals Degradation of Drug Delivery Nanocarriers and Payload Release: A Review of Physical Methods for Tracing Nanocarrier Biological Fate

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 770
Author(s):  
Patrick M. Perrigue ◽  
Richard A. Murray ◽  
Angelika Mielcarek ◽  
Agata Henschke ◽  
Sergio E. Moya
Keyword(s):  
Drug Delivery ◽  
Laser Scanning ◽  
Single Photon ◽  
Photon Emission ◽  
Correlation Spectroscopy ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Emission Computed Tomography ◽  
Systemic Delivery

Nanoformulations offer multiple advantages over conventional drug delivery, enhancing solubility, biocompatibility, and bioavailability of drugs. Nanocarriers can be engineered with targeting ligands for reaching specific tissue or cells, thus reducing the side effects of payloads. Following systemic delivery, nanocarriers must deliver encapsulated drugs, usually through nanocarrier degradation. A premature degradation, or the loss of the nanocarrier coating, may prevent the drug’s delivery to the targeted tissue. Despite their importance, stability and degradation of nanocarriers in biological environments are largely not studied in the literature. Here we review techniques for tracing the fate of nanocarriers, focusing on nanocarrier degradation and drug release both intracellularly and in vivo. Intracellularly, we will discuss different fluorescence techniques: confocal laser scanning microscopy, fluorescence correlation spectroscopy, lifetime imaging, flow cytometry, etc. We also consider confocal Raman microscopy as a label-free technique to trace colocalization of nanocarriers and drugs. In vivo we will consider fluorescence and nuclear imaging for tracing nanocarriers. Positron emission tomography and single-photon emission computed tomography are used for a quantitative assessment of nanocarrier and payload biodistribution. Strategies for dual radiolabelling of the nanocarriers and the payload for tracing carrier degradation, as well as the efficacy of the payload delivery in vivo, are also discussed.

scholarly journals Relationships of Pelvic Vein Diameter and Reflux with Clinical Manifestations of Pelvic Venous Disorder

Diagnostics ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 145
Author(s):  
Sergey Gavrilov ◽  
Anatoly Karalkin ◽  
Nadezhda Mishakina ◽  
Oksana Efremova ◽  
Anastasia Grishenkova
Keyword(s):  
Single Photon ◽  
Photon Emission ◽  
Clinical Manifestations ◽  
Emission Computed Tomography ◽  
Type I ◽  
Pelvic Vein ◽  
Asymptomatic Patients ◽  
Strong Positive Relationship ◽  
Vein Diameter

The causes of chronic pelvic pain (CPP) in patients with pelvic venous disorder (PeVD) are not completely understood. Various authors consider dilation of pelvic veins (PeVs) and pelvic venous reflux (PVR) as the main mechanisms underlying symptomatic forms of PeVD. The aim of this study was to assess relationships of pelvic vein dilation and PVR with clinical manifestations of PeVD. This non-randomized comparative cohort study included 80 female patients with PeVD who were allocated into two groups with symptomatic (n = 42) and asymptomatic (n = 38) forms of the disease. All patients underwent duplex scanning and single-photon emission computed tomography (SPECT) of PeVs with in vivo labeled red blood cells (RBCs). The PeV diameters, the presence, duration and pattern of PVR in the pelvic veins, as well as the coefficient of pelvic venous congestion (CPVC) were assessed. Two groups did not differ significantly in pelvic vein diameters (gonadal veins (GVs): 7.7 ± 1.3 vs. 8.5 ± 0.5 mm; parametrial veins (PVs): 9.8 ± 0.9 vs. 9.5 ± 0.9 mm; and uterine veins (UVs): 5.6 ± 0.2 vs. 5.5 ± 0.6 mm). Despite this, CPVC was significantly higher in symptomatic versus asymptomatic patients (1.9 ± 0.4 vs. 0.7 ± 0.2, respectively; p = 0.008). Symptomatic patients had type II or III PVR, while asymptomatic patients had type I PVR. The reflux duration was found to be significantly greater in symptomatic versus asymptomatic patients (median and interquartile range: 4.0 [3.0; 5.0] vs. 1.0 [0; 2.0] s for GVs, p = 0.008; 4.0 [3.0; 5.0] vs. 1.1 [1.0; 2.0] s for PVs, p = 0.007; and 2.0 [2.0; 3.0] vs. 1.0 [1.0; 2.0] s for UVs, p = 0.04). Linear correlation analysis revealed a strong positive relationship (Pearson’s r = 0.78; p = 0.007) of CPP with the PVR duration but not with vein diameter. The grade of PeV dilation may not be a determining factor in CPP development in patients with PeVD. The presence and duration of reflux in the pelvic veins were found to be predictors of the development of symptomatic PeVD.

scholarly journals Imaging Amyloid-β Deposits In Vivo

2002 ◽  
Vol 22 (9) ◽  
pp. 1035-1041 ◽  
Author(s):  
Brian J. Bacskai ◽  
William E. Klunk ◽  
Chester A. Mathis ◽  
Bradley T. Hyman
Keyword(s):  
Single Photon ◽  
Senile Plaques ◽  
Photon Emission ◽  
Multiphoton Microscopy ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
High Sensitivity ◽  
Emission Computed Tomography ◽  
Tissue Samples

Alzheimer disease (AD) is an illness that can only be diagnosed with certainty with postmortem examination of brain tissue. Tissue samples from afflicted patients show neuronal loss, neurofibrillary tangles (NFTs), and amyloid-β plaques. An imaging technique that permitted in vivo detection of NFTs or amyloid-β plaques would be extremely valuable. For example, chronic imaging of senile plaques would provide a readout of the efficacy of experimental therapeutics aimed at removing these neuropathologic lesions. This review discusses the available techniques for imaging amyloid-β deposits in the intact brain, including magnetic resonance imaging, positron emission tomography, single photon emission computed tomography, and multiphoton microscopy. A variety of agents that target amyloid-β deposits specifically have been developed using one or several of these imaging modalities. The difficulty in developing these tools lies in the need for the agents to cross the blood-brain barrier while recognizing amyloid-β with high sensitivity and specificity. This review describes the progress in developing reagents suitable for in vivo imaging of senile plaques.

Basic principles and technological state of the art: SPECT

ESC CardioMed ◽  
2018 ◽  
pp. 573-577
Author(s):  
Alessia Gimelli ◽  
Riccardo Liga
Keyword(s):  
Single Photon ◽  
Imaging Modality ◽  
Photon Emission ◽  
Nuclear Imaging ◽  
The Body ◽  
Emission Computed Tomography ◽  
Non Invasive ◽  
Photon Emission Computed Tomography ◽  
Invasive Evaluation

Single-photon emission computed tomography (SPECT) photons as a medical imaging technique detects the radiation emitted by radioisotopes injected into the body to provide in vivo measurements of regional tissue function. From its introduction in the cardiologic clinical field, nuclear imaging has classically represented the reference technique for the non-invasive evaluation of myocardial perfusion, becoming the most frequently performed imaging modality for the functional assessment of patients with ischaemic heart disease.

scholarly journals Dopamine transporter imaging in neurodegenerative movement disorders: PET vs. SPECT

2020 ◽  
Vol 8 (5) ◽  
pp. 349-356
Author(s):  
Vera S. Kerstens ◽  
A. Varrone
Keyword(s):  
Dopamine Transporter ◽  
Pet Imaging ◽  
Single Photon ◽  
Relevant Literature ◽  
Photon Emission ◽  
Active Role ◽  
Emission Computed Tomography ◽  
Parkinsonian Syndromes ◽  
Dat Spect

Abstract Purpose The dopamine transporter (DAT) serves as biomarker for parkinsonian syndromes. DAT can be measured in vivo with single-photon emission computed tomography (SPECT) and positron emission tomography (PET). DAT-SPECT is the current clinical molecular imaging standard. However, PET has advantages over SPECT measurements, and PET radioligands with the necessary properties for clinical applications are on the rise. Therefore, it is time to review the role of DAT imaging with SPECT compared to PET. Methods PubMed and Web of Science were searched for relevant literature of the previous 10 years. Four topics for comparison were used: diagnostic accuracy, quantitative accuracy, logistics, and flexibility. Results There are a few studies directly comparing DAT-PET and DAT-SPECT. PET and SPECT both perform well in discriminating neurodegenerative from non-neurodegenerative parkinsonism. Clinical DAT-PET imaging seems feasible only recently, thanks to simplified DAT assessments and better availability of PET radioligands and systems. The higher resolution of PET makes more comprehensive assessments of disease progression in the basal ganglia possible. Additionally, it has the possibility of multimodal target assessment. Conclusion DAT-SPECT is established for differentiating degenerative from non-degenerative parkinsonism. For further differentiation within neurodegenerative Parkinsonian syndromes, DAT-PET has essential benefits. Nowadays, because of wider availability of PET systems and radioligand production centers, and the possibility to use simplified quantification methods, DAT-PET imaging is feasible for clinical use. Therefore, DAT-PET needs to be considered for a more active role in the clinic to take a step forward to a more comprehensive understanding and assessment of Parkinson’s disease.

scholarly journals A Novel Automatic Approach for Calculation of the Specific Binding Ratio in [I-123]FP-CIT SPECT

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 289
Author(s):  
Mahmudur G. M. Rahman ◽  
Muhammad M. Islam ◽  
Tetsuya Tsujikawa ◽  
Hidehiko Okazawa
Keyword(s):  
Single Photon ◽  
Specific Binding ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Automatic Method ◽  
Characteristic Analysis ◽  
Specific Binding Ratio ◽  
Binding Ratio ◽  
Significant Difference ◽  
Fully Automatic

A fully automatic method for specific binding ratio (SBR) calculation in [123I]ioflupane single-photon emission computed tomography (SPECT) studies was proposed by creating volumes of interest of the striatum (VOIst) and reference region (VOIref) without manual handling to avoid operator-induced variability. The study involved 105 patients (72 ± 10 years) suspected of parkinsonian syndrome (PS) who underwent [123I]ioflupane SPECT. The 200 images from our previous study were used for evaluation and validation of the new program. All patients were classified into PS and non-PS groups according to the results of clinical follow-up. A trapezoidal volume of interest (VOIt) containing all striatal intensive counts was created automatically, followed by VOIst setting using the previous method. SBR values were calculated from the mean values of VOIst and VOIref determined by the whole brain outside of VOIt. The low count voxels in the VOIref were excluded using an appropriate threshold. The SBR values from the new method were compared with the previous semi-automatic method and the Tossici–Bolt (TB) method. The SBRs from the semi- and fully automatic methods showed a good linear correlation (r > 0.98). The areas under the curves (AUCs) of receiver operating characteristic analysis showed no significant difference between the two methods for both our previous (AUC > 0.99) and new (AUC > 0.95) data. The diagnostic accuracy of the two methods showed similar results (>92%), and both were better than the TB method. The proposed method successfully created the automatic VOIs and calculated SBR rapidly (9 ± 1 s/patient), avoiding operator-induced variability and providing objective SBR results.

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