Recent Advances in Targeting Nuclear Molecular Imaging Driven by Tetrazine Bioorthogonal Chemistry

2020 ◽  
Vol 27 (23) ◽  
pp. 3924-3943 ◽  
Author(s):  
Ping Dong ◽  
Xueyi Wang ◽  
Junwei Zheng ◽  
Xiaoyang Zhang ◽  
Yiwen Li ◽  
...  

Molecular imaging techniques apply sophisticated technologies to monitor, directly or indirectly, the spatiotemporal distribution of molecular or cellular processes for biomedical, diagnostic, or therapeutic purposes. For example, Single-Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) imaging, the most representative modalities of molecular imaging, enable earlier and more accurate diagnosis of cancer and cardiovascular diseases. New possibilities for noninvasive molecular imaging in vivo have emerged with advances in bioorthogonal chemistry. For example, tetrazine-related Inverse Electron Demand Diels-Alder (IEDDA) reactions can rapidly generate short-lived radioisotope probes in vivo that provide strong contrast for SPECT and PET. Here, we review pretargeting strategies for molecular imaging and novel radiotracers synthesized via tetrazine bioorthogonal chemistry. We systematically describe advances in direct radiolabeling and pretargeting approaches in SPECT and PET using metal and nonmetal radioisotopes based on tetrazine bioorthogonal reactions, and we discuss prospects for the future of such contrast agents.

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 ◽  
...  

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.


2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jinhui Li ◽  
Jing Lu ◽  
You Zhou

The present study aimed to discuss the role of mitochondrion in cardiac function and disease. The mitochondrion plays a fundamental role in cellular processes ranging from metabolism to apoptosis. The mitochondrial-targeted molecular imaging could potentially illustrate changes in global and regional cardiac dysfunction. The collective changes that occur in mitochondrial-targeted molecular imaging probes have been widely explored and developed. As probes currently used in the preclinical setting still have a lot of shortcomings, the development of myocardial metabolic activity, viability, perfusion, and blood flow molecular imaging probes holds great potential for accurately evaluating the myocardial viability and functional reserve. The advantages of molecular imaging provide a perspective on investigating the mitochondrial function of the myocardium in vivo noninvasively and quantitatively. The molecular imaging tracers of single-photon emission computed tomography and positron emission tomography could give more detailed information on myocardial metabolism and restoration. In this study, series mitochondrial-targeted99mTc-,123I-, and18F-labeled tracers displayed broad applications because they could provide a direct link between mitochondrial dysfunction and cardiac disease.


2020 ◽  
Vol 26 (10) ◽  
pp. 1470-1484 ◽  
Author(s):  
Mariane Le Fur ◽  
Iris Y Zhou ◽  
Onofrio Catalano ◽  
Peter Caravan

Abstract Inflammatory bowel disease (IBD) is defined by a chronic relapsing and remitting inflammation of the gastrointestinal tract, with intestinal fibrosis being a major complication. The etiology of IBD remains unknown, but it is thought to arise from a dysregulated and excessive immune response to gut luminal microbes triggered by genetic and environmental factors. To date, IBD has no cure, and treatments are currently directed at relieving symptoms and treating inflammation. The current diagnostic of IBD relies on endoscopy, which is invasive and does not provide information on the presence of extraluminal complications and molecular aspect of the disease. Cross-sectional imaging modalities such as computed tomography enterography (CTE), magnetic resonance enterography (MRE), positron emission tomography (PET), single photon emission computed tomography (SPECT), and hybrid modalities have demonstrated high accuracy for the diagnosis of IBD and can provide both functional and morphological information when combined with the use of molecular imaging probes. This review presents the state-of-the-art imaging techniques and molecular imaging approaches in the field of IBD and points out future directions that could help improve our understanding of IBD pathological processes, along with the development of efficient treatments.


Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5459
Author(s):  
Huiling Li ◽  
Zhen Liu ◽  
Lujie Yuan ◽  
Kevin Fan ◽  
Yongxue Zhang ◽  
...  

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.


2013 ◽  
pp. 159-166
Author(s):  
Giorgio Treglia ◽  
Ernesto Cason ◽  
Giorgio Fagioli

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.


2017 ◽  
Vol 1 ◽  
pp. 247054701771091 ◽  
Author(s):  
Margaret T. Davis ◽  
Sophie E. Holmes ◽  
Robert H. Pietrzak ◽  
Irina Esterlis

Chronic stress accounts for billions of dollars of economic loss annually in the United States alone, and is recognized as a major source of disability and mortality worldwide. Robust evidence suggests that chronic stress plays a significant role in the onset of severe and impairing psychiatric conditions, including major depressive disorder, bipolar disorder, and posttraumatic stress disorder. Application of molecular imaging techniques such as positron emission tomography and single photon emission computed tomography in recent years has begun to provide insight into the molecular mechanisms by which chronic stress confers risk for these disorders. The present paper provides a comprehensive review and synthesis of all positron emission tomography and single photon emission computed tomography imaging publications focused on the examination of molecular targets in individuals with major depressive disorder, posttraumatic stress disorder, or bipolar disorder to date. Critical discussion of discrepant findings and broad strengths and weaknesses of the current body of literature is provided. Recommended future directions for the field of molecular imaging to further elucidate the neurobiological substrates of chronic stress-related disorders are also discussed. This article is part of the inaugural issue for the journal focused on various aspects of chronic stress.


2006 ◽  
Vol 16 (06) ◽  
pp. 1671-1687 ◽  
Author(s):  
A. S. FOKAS ◽  
V. MARINAKIS

The imaging techniques of magnetoencephalography (MEG), computed tomography (CT), positron emission tomography (PET) and single photon emission computed tomography (SPECT) are reviewed, and the analytical solutions of the relevant inverse problems are presented. The numerical implementation of the exact formulas yield accurate reconstructions for both realistic phantoms as well as real data.


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 674 ◽  
Author(s):  
Daniel Harding ◽  
Bernard Prendergast

Infective endocarditis is a heterogeneous condition whose incidence is rising. Despite advances in surgery and diagnostic methods, one-year mortality has not changed and it remains at 30%. Patients with prosthetic valve and intra-cardiac device–related endocarditis are being seen more frequently and this condition is difficult to diagnose with conventional microbiological and imaging techniques. The modified Duke criteria lack sensitivity in this group and should be supplemented with newer imaging techniques, including 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and single-photon emission computed tomography (SPECT). In this article, we discuss these techniques and their role in the diagnosis of infective endocarditis.


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