scholarly journals Molecular Imaging of Apoptosis: The Case of Caspase-3 Radiotracers

2021 ◽  
Vol 22 (8) ◽  
pp. 3948
Author(s):  
Lucas Beroske ◽  
Tim Van den Wyngaert ◽  
Sigrid Stroobants ◽  
Pieter Van der Veken ◽  
Filipe Elvas
Keyword(s):  
Molecular Imaging ◽  
Caspase 3 ◽  
Nuclear Imaging ◽  
High Sensitivity ◽  
Cell Permeability ◽  
Tissue Penetration ◽  
Apoptosis Imaging ◽  
Multiple Biomarkers ◽  
Executioner Caspases ◽  
High Depth

The molecular imaging of apoptosis remains an important method for the diagnosis and monitoring of the progression of certain diseases and the evaluation of the efficacy of anticancer apoptosis-inducing therapies. Among the multiple biomarkers involved in apoptosis, activated caspase-3 is an attractive target, as it is the most abundant of the executioner caspases. Nuclear imaging is a good candidate, as it combines a high depth of tissue penetration and high sensitivity, features necessary to detect small changes in levels of apoptosis. However, designing a caspase-3 radiotracer comes with challenges, such as selectivity, cell permeability and transient caspase-3 activation. In this review, we discuss the different caspase-3 radiotracers for the imaging of apoptosis together with the challenges of the translation of various apoptosis-imaging strategies in clinical trials.

scholarly journals Perfluorocarbon Nanoparticles: Evolution of a Multimodality and Multifunctional Imaging Agent

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Patrick M. Winter
Keyword(s):  
Drug Delivery ◽  
Molecular Imaging ◽  
Particle Surface ◽  
Nuclear Imaging ◽  
High Sensitivity ◽  
The Body ◽  
Low Levels ◽  
Potential Impact ◽  
High Payload

Perfluorocarbon nanoparticles offer a biologically inert, highly stable, and nontoxic platform that can be specifically designed to accomplish a range of molecular imaging and drug delivery functions in vivo. The particle surface can be decorated with targeting ligands to direct the agent to a variety of biomarkers that are associated with diseases such as cancer, cardiovascular disease, obesity, and thrombosis. The surface can also carry a high payload of imaging agents, ranging from paramagnetic metals for MRI, radionuclides for nuclear imaging, iodine for CT, and florescent tags for histology, allowing high sensitivity mapping of cellular receptors that may be expressed at very low levels in the body. In addition to these diagnostic imaging applications, the particles can be engineered to carry highly potent drugs and specifically deposit them into cell populations that display biosignatures of a variety of diseases. The highly flexible and robust nature of this combined molecular imaging and drug delivery vehicle has been exploited in a variety of animal models to demonstrate its potential impact on the care and treatment of patients suffering from some of the most debilitating diseases.

Radiolabeled Peptides for Molecular Imaging of Apoptosis

2020 ◽  
Vol 27 (41) ◽  
pp. 7064-7089
Author(s):  
Mona Mosayebnia ◽  
Maliheh Hajiramezanali ◽  
Soraya Shahhosseini
Keyword(s):  
Nuclear Imaging ◽  
High Sensitivity ◽  
Therapeutic Agents ◽  
Signal Pathways ◽  
Single Cell Level ◽  
Cell Level ◽  
Radiolabeled Peptides ◽  
Physiological Signal ◽  
Apoptosis Imaging ◽  
Regulated Cell Death

Apoptosis is a regulated cell death induced by extrinsic and intrinsic stimulants. Tracking of apoptosis provides an opportunity for the assessment of cardiovascular and neurodegenerative diseases as well as monitoring of cancer therapy at early stages. There are some key mediators in apoptosis cascade, which could be considered as specific targets for delivering imaging or therapeutic agents. The targeted radioisotope-based imaging agents are able to sensitively detect the physiological signal pathways which make them suitable for apoptosis imaging at a single-cell level. Radiopeptides take advantage of both the high sensitivity of nuclear imaging modalities and favorable features of peptide scaffolds. The aim of this study is to review the characteristics of those radiopeptides targeting apoptosis with different mechanisms.

scholarly journals Recent development of nanoparticles for molecular imaging

2017 ◽  
Vol 375 (2107) ◽  
pp. 20170022 ◽  
Author(s):  
Jonghoon Kim ◽  
Nohyun Lee ◽  
Taeghwan Hyeon
Keyword(s):  
Surface Modification ◽  
Molecular Imaging ◽  
Contrast Agents ◽  
Multimodal Imaging ◽  
High Sensitivity ◽  
Accurate Diagnosis ◽  
Biological Processes ◽  
Future Perspectives ◽  
Cellular Functions ◽  
Diagnosis Of Diseases

Molecular imaging enables us to non-invasively visualize cellular functions and biological processes in living subjects, allowing accurate diagnosis of diseases at early stages. For successful molecular imaging, a suitable contrast agent with high sensitivity is required. To date, various nanoparticles have been developed as contrast agents for medical imaging modalities. In comparison with conventional probes, nanoparticles offer several advantages, including controllable physical properties, facile surface modification and long circulation time. In addition, they can be integrated with various combinations for multimodal imaging and therapy. In this opinion piece, we highlight recent advances and future perspectives of nanomaterials for molecular imaging. This article is part of the themed issue ‘Challenges for chemistry in molecular imaging’.

scholarly journals Phylogenetic analysis of the caspase family in bivalves: implications for programmed cell death, immune response and development

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Susanne Vogeler ◽  
Stefano Carboni ◽  
Xiaoxu Li ◽  
Alyssa Joyce
Keyword(s):  
Immune Response ◽  
Caspase 3 ◽  
Developmental Stages ◽  
Phylogenetic Analyses ◽  
Apoptotic Pathway ◽  
Caspase Family ◽  
Executioner Caspases ◽  
And Function ◽  
Relationship Of ◽  
Inflammatory Caspases

Abstract Background Apoptosis is an important process for an organism’s innate immune system to respond to pathogens, while also allowing for cell differentiation and other essential life functions. Caspases are one of the key protease enzymes involved in the apoptotic process, however there is currently a very limited understanding of bivalve caspase diversity and function. Results In this work, we investigated the presence of caspase homologues using a combination of bioinformatics and phylogenetic analyses. We blasted the Crassostrea gigas genome for caspase homologues and identified 35 potential homologues in the addition to the already cloned 23 bivalve caspases. As such, we present information about the phylogenetic relationship of all identified bivalve caspases in relation to their homology to well-established vertebrate and invertebrate caspases. Our results reveal unexpected novelty and complexity in the bivalve caspase family. Notably, we were unable to identify direct homologues to the initiator caspase-9, a key-caspase in the vertebrate apoptotic pathway, inflammatory caspases (caspase-1, − 4 or − 5) or executioner caspases-3, − 6, − 7. We also explored the fact that bivalves appear to possess several unique homologues to the initiator caspase groups − 2 and − 8. Large expansions of caspase-3 like homologues (caspase-3A-C), caspase-3/7 group and caspase-3/7-like homologues were also identified, suggesting unusual roles of caspases with direct implications for our understanding of immune response in relation to common bivalve diseases. Furthermore, we assessed the gene expression of two initiator (Cg2A, Cg8B) and four executioner caspases (Cg3A, Cg3B, Cg3C, Cg3/7) in C. gigas late-larval development and during metamorphosis, indicating that caspase expression varies across the different developmental stages. Conclusion Our analysis provides the first overview of caspases across different bivalve species with essential new insights into caspase diversity, knowledge that can be used for further investigations into immune response to pathogens or regulation of developmental processes.

scholarly journals Identification of FDA-approved drugs as novel allosteric inhibitors of human executioner caspases

2018 ◽  
Author(s):  
R. N. V. Krishna Deepak ◽  
Ahmad Abdullah ◽  
Priti Talwar ◽  
Hao Fan ◽  
Palaniyandi Ravanan
Keyword(s):  
Active Site ◽  
Caspase 3 ◽  
Specific Activity ◽  
Special Importance ◽  
Allosteric Inhibitors ◽  
Dimerization Interface ◽  
Executioner Caspases ◽  
Approved Drugs ◽  
Fda Approved Drugs

AbstractThe regulation of apoptosis is a tightly-coordinated process and caspases are its chief regulators. Of special importance are the executioner caspases, caspase-3/7, the activation of which irreversibly sets the cell on the path of death. Dysregulation of apoptosis, particularly an increased rate of cell death lies at the root of numerous human diseases. Although several peptide-based inhibitors targeting the homologous active site region of caspases have been developed, owing to their non-specific activity and poor pharmacological properties their use has largely been restricted. Thus, we sought to identify FDA-approved drugs that could be repurposed as novel allosteric inhibitors of caspase-3/7. In this study, we virtually screened a catalog of FDA-approved drugs targeting an allosteric pocket located at the dimerization interface of caspase-3/7. From among the top-scoring hits we short-listed five compounds for experimental validation. Our enzymatic assays using recombinant caspase-3 suggested that four out of the five drugs effectively inhibited caspase-3 enzymatic activity in vitro with IC50 values ranging ~10-55 μM. Structural analysis of the docking poses show the four compounds forming specific non-covalent interactions at the allosteric pocket suggesting that these molecules could disrupt the adjacently-located active site. In summary, we report the identification of four novel non-peptide allosteric inhibitors of caspase-3/7 from among FDA-approved drugs.

In Vivo Evaluation of Radiofluorinated Caspase-3/7 Inhibitors as Radiotracers for Apoptosis Imaging and Comparison with [18F]ML-10 in a Stroke Model in the Rat

2015 ◽  
Vol 18 (1) ◽  
pp. 117-126 ◽  
Author(s):  
Marie Médoc ◽  
Martine Dhilly ◽  
Lidia Matesic ◽  
Jérôme Toutain ◽  
Anwen M. Krause-Heuer ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Stroke Model ◽  
In Vivo Evaluation ◽  
Apoptosis Imaging

6-[ 18 f]Fluorodopamine Positron Emission Tomographic (PET) Scanning in the Diagnostic Localization of Pheochromocytoma

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 714-715
Author(s):  
David S Goldstein ◽  
Graeme Eisenhofer ◽  
Sheng-Ting Li ◽  
Karel Pacak
Keyword(s):  
Nuclear Imaging ◽  
High Sensitivity ◽  
Good Sensitivity ◽  
Positron Emission Tomographic ◽  
Resonance Imaging ◽  
Positron Emission ◽  
Pet Scanning ◽  
Pet Scans ◽  
Initial Results ◽  
Limited Sensitivity

P119 The diagnosis and treatment of pheochromocytoma (PHEO) depend on means to localize the tumor. Computed tomography and magnetic resonance imaging have good sensitivity but poor specificity, and nuclear imaging has limited sensitivity. Here we report initial results of 6-[ 18 F]Fluorodopamine PET scanning in patients with known or suspected PHEO. Of 23 patients, 13 had the tumor. Ten had normal plasma levels of metanephrines, excluding PHEO. All 13 patients with PHEO had abnormal fluorodopamine PET scans that identified the tumors. The 10 patients without PHEO had negative PET scans. Fluorodopamine PET scanning detects PHEO with high sensitivity.

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