scholarly journals Striatal dopamine D2/3 receptors in medication-naïve schizophrenia: an [123I] IBZM SPECT study

2021 ◽  
pp. 1-9
Author(s):  
Kao Chin Chen ◽  
Yen Kuang Yang ◽  
Oliver D. Howes ◽  
I Hui Lee ◽  
Tzung Lieh Yeh ◽  
...  
Keyword(s):  
Single Photon ◽  
Imaging Techniques ◽  
Photon Emission ◽  
Striatal Dopamine ◽  
Dopamine Synthesis ◽  
Emission Computed Tomography ◽  
Healthy Controls ◽  
Recent Onset ◽  
Significant Difference ◽  
The Mean

Abstract Background The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels. Methods We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia. Result The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI −0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = −0.01(binding ratio); 95% CI −0.01 to −0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores. Conclusions Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.

scholarly journals Standardization of the [68Ga]Ga-PSMA-11 Radiolabeling Protocol in an Automatic Synthesis Module: Assessments for PET Imaging of Prostate Cancer

2021 ◽  
Vol 14 (5) ◽  
pp. 385
Author(s):  
Leonardo L. Fuscaldi ◽  
Danielle V. Sobral ◽  
Ana Claudia R. Durante ◽  
Fernanda F. Mendonça ◽  
Ana Cláudia C. Miranda ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Pet Imaging ◽  
Saline Solution ◽  
Serum Proteins ◽  
Single Photon ◽  
Imaging Techniques ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Lncap Cells ◽  
Automatic Synthesis

Prostate-specific membrane antigen (PSMA) is a glycoprotein present in the prostate, that is overexpressed in prostate cancer (PCa). Recently, PSMA-directed radiopharmaceuticals have been developed, allowing the pinpointing of tumors with the Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) imaging techniques. The aim of the present work was to standardize and validate an automatic synthesis module-based radiolabeling protocol for [68Ga]Ga-PSMA-11, as well as to produce a radiopharmaceutical for PET imaging of PCa malignancies. [68Ga]Ga-PSMA-11 was evaluated to determine the radiochemical purity (RCP), stability in saline solution and serum, lipophilicity, affinity to serum proteins, binding and internalization to lymph node carcinoma of the prostate (LNCaP) cells, and ex vivo biodistribution in mice. The radiopharmaceutical was produced with an RCP of 99.06 ± 0.10%, which was assessed with reversed-phase high-performance liquid chromatography (RP-HPLC). The product was stable in saline solution for up to 4 h (RCP > 98%) and in serum for up to 1 h (RCP > 95%). The lipophilicity was determined as −3.80 ± 0.15, while the serum protein binding (SPB) was <17%. The percentages of binding to LNCaP cells were 4.07 ± 0.51% (30 min) and 4.56 ± 0.46% (60 min), while 19.22 ± 2.73% (30 min) and 16.85 ± 1.34% (60 min) of bound material was internalized. High accumulation of [68Ga]Ga-PSMA-11 was observed in the kidneys, spleen, and tumor, with a tumor-to-contralateral-muscle ratio of >8.5 and a tumor-to-blood ratio of >3.5. In conclusion, an automatic synthesis module-based radiolabeling protocol for [68Ga]Ga-PSMA-11 was standardized and the product was evaluated, thus verifying its characteristics for PET imaging of PCa tumors in a clinical environment.

scholarly journals INTEGRATION OF COMPLEMENTARY BIOMARKERS IN PATIENTS WITH FIRST EPISODE PSYCHOSIS: RESEARCH PROTOCOL OF A PROSPECTIVE FOLLOW UP STUDY

2019 ◽  
Author(s):  
Petra ◽  
Martina Rojnic Kuzman ◽  
Porin Makaric ◽  
Dina Bosnjak Kuharic ◽  
Ivana Kekin ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Single Photon ◽  
Single Gene ◽  
Photon Emission ◽  
Blood Perfusion ◽  
First Episode ◽  
Emission Computed Tomography ◽  
Healthy Controls ◽  
Post Mortem

In this project, we recruited a sample of 150 patients with first episode of psychosis with schizophrenia features (FEP) and 100 healthy controls. We assessed the differences between these two groups, as well as the changes between the acute phase of illness and subsequent remission among patients over 18-month longitudinal follow-up. The assessments were divided into four work packages (WP): WP1- psychopathological status, neurocognitive functioning and emotional recognition; WP2- stress response measured by saliva cortisol during a stress paradigm; cerebral blood perfusion in the resting state (with single photon emission computed tomography (SPECT) and during activation paradigm (with Transcranial Ultrasonography Doppler (TCD); WP3-post mortem analysis in histologically prepared human cortical tissue of post mortem samples of subjects with schizophrenia in the region that synaptic alteration was suggested by WP1 and WP2; WP4- pharmacogenetic analysis (single gene polymorphisms and genome wide association study (GWAS). We expect that the analysis of these data will identify a set of markers that differentiate healthy controls from patients with FEP, and serve as an additional diagnostic tool in the first episode of psychosis, and prediction tool which can be then used to help tailoring individualized treatment options. In this paper, we describe the project protocol including aims and methods and provide a brief description of planned post mortem studies and pharmacogenetic analysis.

scholarly journals Radionuclide-Based Imaging of Breast Cancer: State of the Art

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5459
Author(s):  
Huiling Li ◽  
Zhen Liu ◽  
Lujie Yuan ◽  
Kevin Fan ◽  
Yongxue Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Imaging ◽  
Single Photon ◽  
Morphological Changes ◽  
Imaging Techniques ◽  
Rapid Development ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Biological Processes ◽  
Functional Perspective

Breast cancer is a malignant tumor that can affect women worldwide and endanger their health and wellbeing. Early detection of breast cancer can significantly improve the prognosis and survival rate of patients, but with traditional anatomical imagine methods, it is difficult to detect lesions before morphological changes occur. Radionuclide-based molecular imaging based on positron emission tomography (PET) and single-photon emission computed tomography (SPECT) displays its advantages for detecting breast cancer from a functional perspective. Radionuclide labeling of small metabolic compounds can be used for imaging biological processes, while radionuclide labeling of ligands/antibodies can be used for imaging receptors. Noninvasive visualization of biological processes helps elucidate the metabolic state of breast cancer, while receptor-targeted radionuclide molecular imaging is sensitive and specific for visualization of the overexpressed molecular markers in breast cancer, contributing to early diagnosis and better management of cancer patients. The rapid development of radionuclide probes aids the diagnosis of breast cancer in various aspects. These probes target metabolism, amino acid transporters, cell proliferation, hypoxia, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), gastrin-releasing peptide receptor (GRPR) and so on. This article provides an overview of the development of radionuclide molecular imaging techniques present in preclinical or clinical studies, which are used as tools for early breast cancer diagnosis.

Nuclear cardiology: state of the art

Heart ◽  
2021 ◽  
pp. heartjnl-2019-315628
Author(s):  
Rebecca Schofield ◽  
Leon Menezes ◽  
Stephen Richard Underwood
Keyword(s):  
Heart Failure ◽  
Myocardial Perfusion ◽  
Radionuclide Imaging ◽  
Single Photon ◽  
Imaging Techniques ◽  
Sympathetic Innervation ◽  
Photon Emission ◽  
Myocardial Inflammation ◽  
Emission Computed Tomography ◽  
Device Infection

Radionuclide imaging remains an essential component of modern cardiology. There is overlap with the information from other imaging techniques, but no technique is static and new developments have expanded its role. This review focuses on ischaemic heart disease, heart failure, infection and inflammation. Radiopharmaceutical development includes the wider availability of positron emission tomography (PET) tracers such as rubidium-82, which allows myocardial perfusion to be quantified in absolute terms. Compared with alternative techniques, myocardial perfusion scintigraphy PET and single photon emission computed tomography (SPECT) have the advantages of being widely applicable using exercise or pharmacological stress, full coverage of the myocardium and a measure of ischaemic burden, which helps to triage patients between medical therapy and revascularisation. Disadvantages include the availability of expertise in some cardiac centres and the lack of simple SPECT quantification, meaning that global abnormalities can be underestimated. In patients with heart failure, despite the findings of the STICH (Surgical Treatment for Ischemic Heart Failure) trial, there are still data to support the assessment of myocardial hibernation in predicting when abolition of ischaemia might lead to improvement in ventricular function. Imaging of sympathetic innervation is well validated, but simpler markers of prognosis mean that it has not been widely adopted. There are insufficient data to support its use in predicting the need for implanted devices, but non-randomised studies are promising. Other areas where radionuclide imaging is uniquely valuable are detection and monitoring of endocarditis, device infection, myocardial inflammation in sarcoidosis, myocarditis and so on, and reliable detection of deposition in suspected transthyretin-related amyloidosis.

scholarly journals O5.1. STRIATAL DOPAMINE AND REDUCED REWARD PREDICTION ERROR SIGNALING IN UNMEDICATED SCHIZOPHRENIA PATIENTS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S11-S11
Author(s):  
Teresa Katthagen ◽  
Jakob Kaminski ◽  
Andreas Heinz ◽  
Ralph Buchert ◽  
Florian Schlagenhauf
Keyword(s):  
Prediction Error ◽  
Negative Symptoms ◽  
Ventral Striatum ◽  
Striatal Dopamine ◽  
Dopamine Synthesis ◽  
Positive Symptoms ◽  
Healthy Controls ◽  
Reward Prediction Error ◽  
Reward Prediction ◽  
Significant Difference

Abstract Background Increased striatal dopamine synthesis capacity (DSC) has consistently been reported in patients with schizophrenia (Sz). However, the functional mechanism translating this into behavior and symptoms remains unclear. It has been proposed that heightened striatal dopamine may blunt dopaminergic reward prediction error (RPE) signaling during reinforcement learning. Methods In this study, we investigated striatal DSC and RPEs and their association in unmedicated Sz and healthy controls. 23 healthy controls (HC) and 20 unmedicated Sz took part in an FDOPA-PET scan measuring DSC and underwent fMRI scanning, where they performed a reversal learning paradigm. We compared groups regarding DSC und neural RPE signals and probed the respective correlation (23 HC and 16 Sz for both measures). Results There was no significant difference between HC and Sz in DSC. Taking into account comorbid alcohol abuse revealed that only patients without such abuse showed elevated DSC in the associative and sensorimotor striatum, while those with abuse did not differ from HC. Patients performed worse during learning, accompanied by a reduced RPE signal in the ventral striatum. In HC, the DSC in the limbic striatum correlated with higher RPE signaling, while there was no significant association in patients. DSC in the associative striatum correlated with higher positive symptoms, and blunted RPE signaling was associated with negative symptoms. Discussion Our results suggest that dopamine modulation of RPE is impaired in schizophrenia. Furthermore, we observed a dissociation with elevated DSC in the associative and sensorimotor striatum contributing to positive symptoms and blunted RPE in the ventral striatum to negative symptoms.

scholarly journals Recent applications of nuclear medicine in diagnostics: II part

2013 ◽  
pp. 159-166
Author(s):  
Giorgio Treglia ◽  
Ernesto Cason ◽  
Giorgio Fagioli
Keyword(s):  
Nuclear Medicine ◽  
Single Photon ◽  
Imaging Techniques ◽  
Photon Emission ◽  
Cellular Level ◽  
Accurate Information ◽  
Emission Computed Tomography ◽  
Nuclear Medicine Imaging ◽  
Positron Emission ◽  
Artery Disease

Introduction: Positron-emission tomography (PET) and single photon emission computed tomography (SPECT) are effective diagnostic imaging tools in several clinical settings. The aim of this article (the second of a 2-part series) is to examine some of the more recent applications of nuclear medicine imaging techniques, particularly in the fields of neurology, cardiology, and infection/inflammation. Discussion: A review of the literature reveals that in the field of neurology nuclear medicine techniques are most widely used to investigate cognitive deficits and dementia (particularly those associated with Alzheimer disease), epilepsy, and movement disorders. In cardiology, SPECT and PET also play important roles in the work-up of patients with coronary artery disease, providing accurate information on the state of the myocardium (perfusion, metabolism, and innervation). White blood cell scintigraphy and FDG-PET are widely used to investigate many infectious/inflammatory processes. In each of these areas, the review discusses the use of recently developed radiopharmaceuticals, the growth of tomographic nuclear medicine techniques, and the ways in which these advances are improving molecular imaging of biologic processes at the cellular level.

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.

scholarly journals Development of Antibody Immuno-PET/SPECT Radiopharmaceuticals for Imaging of Oncological Disorders—An Update

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1868
Author(s):  
Jonatan Dewulf ◽  
Karuna Adhikari ◽  
Christel Vangestel ◽  
Tim Van Den Wyngaert ◽  
Filipe Elvas
Keyword(s):  
Clinical Decision Making ◽  
Single Photon ◽  
Imaging Techniques ◽  
Photon Emission ◽  
Therapy Response ◽  
High Specificity ◽  
Clinical Decision ◽  
Disease Diagnosis ◽  
Emission Computed Tomography ◽  
Wide Range

Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are molecular imaging strategies that typically use radioactively labeled ligands to selectively visualize molecular targets. The nanomolar sensitivity of PET and SPECT combined with the high specificity and affinity of monoclonal antibodies have shown great potential in oncology imaging. Over the past decades a wide range of radio-isotopes have been developed into immuno-SPECT/PET imaging agents, made possible by novel conjugation strategies (e.g., site-specific labeling, click chemistry) and optimization and development of novel radiochemistry procedures. In addition, new strategies such as pretargeting and the use of antibody fragments have entered the field of immuno-PET/SPECT expanding the range of imaging applications. Non-invasive imaging techniques revealing tumor antigen biodistribution, expression and heterogeneity have the potential to contribute to disease diagnosis, therapy selection, patient stratification and therapy response prediction achieving personalized treatments for each patient and therefore assisting in clinical decision making.

scholarly journals Ocular Biodistribution Studies Using Molecular Imaging

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 237 ◽  
Author(s):  
Ana Castro-Balado ◽  
Cristina Mondelo-García ◽  
Miguel González-Barcia ◽  
Irene Zarra-Ferro ◽  
Francisco J Otero-Espinar ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Single Photon ◽  
Imaging Techniques ◽  
Photon Emission ◽  
High Sensitivity ◽  
New Drugs ◽  
Emission Computed Tomography ◽  
Pharmacokinetic Data ◽  
Biodistribution Studies

Classical methodologies used in ocular pharmacokinetics studies have difficulties to obtain information about topical and intraocular distribution and clearance of drugs and formulations. This is associated with multiple factors related to ophthalmic physiology, as well as the complexity and invasiveness intrinsic to the sampling. Molecular imaging is a new diagnostic discipline for in vivo imaging, which is emerging and spreading rapidly. Recent developments in molecular imaging techniques, such as positron emission tomography (PET), single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI), allow obtaining reliable pharmacokinetic data, which can be translated into improving the permanence of the ophthalmic drugs in its action site, leading to dosage optimisation. They can be used to study either topical or intraocular administration. With these techniques it is possible to obtain real-time visualisation, localisation, characterisation and quantification of the compounds after their administration, all in a reliable, safe and non-invasive way. None of these novel techniques presents simultaneously high sensitivity and specificity, but it is possible to study biological procedures with the information provided when the techniques are combined. With the results obtained, it is possible to assume that molecular imaging techniques are postulated as a resource with great potential for the research and development of new drugs and ophthalmic delivery systems.

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