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

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.

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Early environmental enrichment and impoverishment differentially affect addiction-related behavioral traits, cocaine-taking, and dopamine D2/3 receptor signaling in a rat model of vulnerability to drug abuse

Psychopharmacology ◽

10.1007/s00213-021-05971-z ◽

2021 ◽

Author(s):

Lidia Bellés ◽

Andrea Dimiziani ◽

François R. Herrmann ◽

Nathalie Ginovart

Keyword(s):

Environmental Enrichment ◽

Single Photon ◽

Photon Emission ◽

Emission Computed Tomography ◽

Novelty Preference ◽

Self Administration ◽

Rearing Environment ◽

Behavioral Traits ◽

Da Release ◽

Early Rearing

Abstract Rationale Risk factors for drug addiction include genetics, environment, and behavioral traits such as impulsivity and novelty preference (NP), which have been related to deficits in striatal dopamine (DA) D2/3-receptors (D2/3R) and heightened amphetamine (AMPH)-induced DA release. However, the influence of the early rearing environment on these behavioral and neurochemical variables is not clear. Objectives We investigated the influence of early rearing environment on striatal D2/3R availabilities and AMPH-induced DA release in relation to impulsivity, NP, and propensity to drug self-administration (SA) in “addiction-prone” Roman high- (RHA) and “addiction-resistant” Roman low-avoidance (RLA) rats. Methods Animals were reared post-weaning in either environmental enrichment (EE) or impoverishment (EI) and were assessed at adulthood for impulsivity, NP, and propensity to cocaine SA. EE and EI rats were also scanned using single-photon emission computed tomography to concurrently measure in vivo striatal D2/3R availability and AMPH-induced DA release. Results EE vs. EI was associated with heightened impulsivity and a lack of NP in both rat lines. Higher dorsal striatal D2/3R densities were found in RHA EE and higher AMPH-induced DA release in RLA EE. Both impulsivity and NP were negatively correlated to dorsal striatal D2/3R availabilities and positively correlated with AMPH-induced DA release in EI but not in EE. EE vs. EI was related to a faster rate of cocaine intake and elevated active timeout responses in RHAs. Conclusion Our results suggest non-monotonic, environment-dependent, relationships between impulsivity, NP, and D2/3R-mediated signaling, and suggest that EI vs. EE may decrease the reinforcing effects of psychostimulants in predisposed individuals.

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NIRF-Molecular Imaging with Synovial Macrophages-Targeting Vsig4 Nanobody for Disease Monitoring in a Mouse Model of Arthritis

International Journal of Molecular Sciences ◽

10.3390/ijms20133347 ◽

2019 ◽

Vol 20 (13) ◽

pp. 3347 ◽

Cited By ~ 2

Author(s):

Fang Zheng ◽

Siyu Luo ◽

Zhenlin Ouyang ◽

Jinhong Zhou ◽

Huanye Mo ◽

...

Keyword(s):

Fluorescence Microscopy ◽

Near Infrared ◽

Single Photon ◽

Ex Vivo ◽

Photon Emission ◽

Joint Inflammation ◽

Experimental Arthritis ◽

Emission Computed Tomography ◽

Nirf Imaging

Nanobody against V-set and Ig domain-containing 4 (Vsig4) on tissue macrophages, such as synovial macrophages, could visualize joint inflammation in multiple experimental arthritis models via single-photon emission computed tomography imaging. Here, we further addressed the specificity and assessed the potential for arthritis monitoring using near-infrared fluorescence (NIRF) Cy7-labeled Vsig4 nanobody (Cy7-Nb119). In vivo NIRF-imaging of collagen-induced arthritis (CIA) was performed using Cy7-Nb119. Signals obtained with Cy7-Nb119 or isotope control Cy7-NbBCII10 were compared in joints of naive mice versus CIA mice. In addition, pathological microscopy and fluorescence microscopy were used to validate the arthritis development in CIA. Cy7-Nb119 accumulated in inflamed joints of CIA mice, but not the naive mice. Development of symptoms in CIA was reflected in increased joint accumulation of Cy7-Nb119, which correlated with the conventional measurements of disease. Vsig4 is co-expressed with F4/80, indicating targeting of the increasing number of synovial macrophages associated with the severity of inflammation by the Vsig4 nanobody. NIRF imaging with Cy7-Nb119 allows specific assessment of inflammation in experimental arthritis and provides complementary information to clinical scoring for quantitative, non-invasive and economical monitoring of the pathological process. Nanobody labelled with fluorescence can also be used for ex vivo validation experiments using flow cytometry and fluorescence microscopy.

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A Dual-Labeled Annexin A5 is not Suited for SPECT Imaging of Brain Cell Death in Experimental Murine Stroke

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.115 ◽

2014 ◽

Vol 34 (9) ◽

pp. e1-e7 ◽

Cited By ~ 4

Author(s):

Marietta Zille ◽

Denise Harhausen ◽

Marijke De Saint-Hubert ◽

Roger Michel ◽

Chris P Reutelingsperger ◽

...

Keyword(s):

Cell Death ◽

Fluorescence Microscopy ◽

Single Photon ◽

Ex Vivo ◽

Photon Emission ◽

Spect Imaging ◽

Experimental Stroke ◽

Emission Computed Tomography ◽

Annexin A5

Cell death is one of the pathophysiological hallmarks after stroke. Markers to image cell death pathways in vivo are highly desirable. We previously showed that fluorescently labeled Annexin A5 (An×A5), which binds specifically to phosphatidylserine (PS) on dead/dying cells, can be used in experimental stroke for monitoring cell death with optical imaging. Here we investigated whether dual-labeled An×A5 (technetium and fluorescence label) can be used for single-photon emission computed tomography (SPECT) of cell death in the same model. C57Bl6/N mice were subjected to 60-minute middle cerebral artery occlusion (MCAO) and underwent SPECT imaging at 24, 48, and 72 hours afterwards. They were injected intravenously with either PS-binding An×A5 or the nonfunctional An×A5 (negative control), labeled with 99mTc and Alexa Fluor 568, respectively. After SPECT imaging, brain sections were cut for autoradiography and fluorescence microscopy. Ethanol-induced cell death in the femur muscle was used as positive control. We detected dual-labeled An×A5 in the model of ethanol-induced cell death in the femur muscle, but not after MCAO at any time point, either with SPECT or with ex vivo autoradiography or fluorescence microscopy. Dual-labeled An×A5 appears to be unsuited for visualizing death of brain cells in this MCAO model.

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In situ lymphoma imaging in a spontaneous mouse model using the Cerenkov Luminescence of F-18 and Ga-67 isotopes

10.21203/rs.3.rs-289118/v1 ◽

2021 ◽

Author(s):

Zsombor Ritter ◽

Katalin Zámbó ◽

Péter Balogh ◽

Dávid Szöllősi ◽

Xinkai Jia ◽

...

Keyword(s):

Lymph Nodes ◽

Single Photon ◽

Ex Vivo ◽

Photon Emission ◽

Emission Computed Tomography ◽

Advanced Stage ◽

Terminal Stage ◽

Imaging Results ◽

67Ga Citrate

Abstract We aimed to study lymphoma diagnostics by Cerenkov luminescence imaging (CLI). We monitored the dissemination of a spontaneous high-grade mouse lymphoma (Bc.DLFL1) in early stage; advanced stage; and terminal stage with in vivo 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) / magnetic resonance imaging (MRI) and 67Ga-citrate single photon emission computed tomography (SPECT) / MRI. In vivo imaging was combined with ex vivo high resolution CLI. The use of CLI with Fluorine-18 and Gallium-67 to select infiltrated lymph nodes for tumor staging pathology was thus tested. At advanced stage, [18F]FDG PET/MRI plus ex vivo CLI allowed accurate detection of [18F]FDG accumulation in lymphoma-infiltrated tissues. At terminal stage we detected tumorous lymph nodes with SPECT/MRI and we could report the Cerenkov light emission of 67Ga. CLI with 67Ga-citrate revealed lymphoma accumulation in distant lymph node locations, unnoticeable with only MRI. Flow cytometry and immunohistochemistry confirmed these imaging results. Our study promotes the combined use of PET and CLI in preclinical studies and clinical practice. Heterogeneous [18F]FDG distribution in lymph nodes detected at sampling surgery has implications for tissue pathology processing and could direct therapy. The results with 67Ga also point to the opportunities to further apply suitable SPECT radiopharmaceuticals for CLI.

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

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557519666190304120011 ◽

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.

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

Pharmaceutics ◽

10.3390/pharmaceutics13060770 ◽

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.

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Visualisation of interstitial lung disease by molecular imaging of integrin αvβ3 and somatostatin receptor 2

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-214322 ◽

2018 ◽

Vol 78 (2) ◽

pp. 218-227 ◽

Cited By ~ 10

Author(s):

Janine Schniering ◽

Martina Benešová ◽

Matthias Brunner ◽

Stephanie Haller ◽

Susan Cohrs ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Single Photon ◽

Ex Vivo ◽

Somatostatin Receptor ◽

Photon Emission ◽

Nuclear Imaging ◽

Integrin Αvβ3 ◽

Biodistribution Studies

ObjectiveTo evaluate integrin αvβ3 (alpha-v-beta-3)-targeted and somatostatin receptor 2 (SSTR2)-targeted nuclear imaging for the visualisation of interstitial lung disease (ILD).MethodsThe pulmonary expression of integrin αvβ3 and SSTR2 was analysed in patients with different forms of ILD as well as in bleomycin (BLM)-treated mice and respective controls using immunohistochemistry. Single photon emission CT/CT (SPECT/CT) was performed on days 3, 7 and 14 after BLM instillation using the integrin αvβ3-targeting 177Lu-DOTA-RGD and the SSTR2-targeting 177Lu-DOTA-NOC radiotracer. The specific pulmonary accumulation of the radiotracers over time was assessed by in vivo and ex vivo SPECT/CT scans and by biodistribution studies.ResultsExpression of integrin αvβ3 and SSTR2 was substantially increased in human ILD regardless of the subtype. Similarly, in lungs of BLM-challenged mice, but not of controls, both imaging targets were stage-specifically overexpressed. While integrin αvβ3 was most abundantly upregulated on day 7, the inflammatory stage of BLM-induced lung fibrosis, SSTR2 expression peaked on day 14, the established fibrotic stage. In agreement with the findings on tissue level, targeted nuclear imaging using SPECT/CT specifically detected both imaging targets ex vivo and in vivo, and thus visualised different stages of experimental ILD.ConclusionOur preclinical proof-of-concept study suggests that specific visualisation of molecular processes in ILD by targeted nuclear imaging is feasible. If transferred into clinics, where imaging is considered an integral part of patients’ management, the additional information derived from specific imaging tools could represent a first step towards precision medicine in ILD.

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

Diagnostics ◽

10.3390/diagnostics12010145 ◽

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.

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Imaging Amyloid-β Deposits In Vivo

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200209000-00001 ◽

2002 ◽

Vol 22 (9) ◽

pp. 1035-1041 ◽

Cited By ~ 76

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.

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Basic principles and technological state of the art: SPECT

ESC CardioMed ◽

10.1093/med/9780198784906.003.0119_update_001 ◽

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.

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