scholarly journals An insight into tumoral hypoxia: the radiomarkers and clinical applications

2011 ◽  
Vol 3 (1) ◽  
pp. 3
Author(s):  
Ana Margarida Abrantes ◽  
Maria Elisa Serra ◽  
Dina Murtinho ◽  
Antonio Rocha Gonsalves ◽  
Maria Filomena Botelho
Keyword(s):  
Single Photon ◽  
Cellular Functions ◽  
O2 Concentration ◽  
Structural Abnormalities ◽  
Imaging Probes ◽  
Cellular Hypoxia ◽  
O2 Diffusion ◽  
Positron Emitters ◽  
Tumoral Hypoxia

Tumoral hypoxia is related to severe structural abnormalities of tumor microvessels, leading to deteriorated O2 diffusion. This decreased O2 concentration in cancer cells compromises cellular functions, besides being responsible for resistance to radiation therapy. Consequently, it is very important to know the hypoxic status of a tumor. In this review, the different methodologies available for evaluating cellular hypoxia in vivo are discussed, particularly those in which the hypoxia information is obtained through imaging. Among these the nuclear medicine approach uses ligands to complex with radionuclides. The resulting radioactive complexes which may be single photon or positron emitters, are very useful as imaging probes. The nature of ligands and their corresponding complexes, with application or potential application as hypoxia detectors, will be described. A summary of the most significant results so far obtained in clinical or preclinical applications will also be discussed.

scholarly journals Mitochondrial-Targeted Molecular Imaging in Cardiac Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jinhui Li ◽  
Jing Lu ◽  
You Zhou
Keyword(s):  
Molecular Imaging ◽  
Cardiac Disease ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Positron Emission ◽  
Molecular Imaging Probes ◽  
Imaging Probes ◽  
Targeted Molecular Imaging

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.

Optical imaging probes and their potential contribution to radiotracer development

2016 ◽  
Vol 55 (02) ◽  
pp. 51-62 ◽  
Author(s):  
S. Hermann ◽  
M. Schäfers ◽  
C. Höltke ◽  
A. Faust
Keyword(s):  
Optical Imaging ◽  
Fluorescent Dyes ◽  
Great Influence ◽  
Potential Contribution ◽  
Preclinical Evaluation ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Imaging Probes ◽  
Unspecific Binding

SummaryOptical imaging has long been considered a method for histological or microscopic investigations. Over the last 15 years, however, this method was applied for preclinical molecular imaging and, just recently, was also able to show its principal potential for clinical applications (e.g. fluorescence-guided surgery). Reviewing the development and preclinical evaluation of new fluorescent dyes and target-specific dye conjugates, these often show characteristic patterns of their routes of excretion and biodistribution, which could also be interesting for the development and optimization of radiopharmaceuticals. Especially ionic charges show a great influence on biodistribution and netcharge and charge-distribution on a conjugate often determines unspecific binding or background signals in liver, kidney or intestine, and other organs.Learning from fluorescent probe behaviour in vivo and translating this knowledge to radio-pharmaceuticals might be useful to further optimize emerging and existing radiopharmaceuticals with respect to their biodistribution and thereby availability for binding to their targets.

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.

Inhibition of dihydropyridine-sensitive calcium entry in hypoxic relaxation of airway smooth muscle

1995 ◽  
Vol 268 (2) ◽  
pp. L201-L206 ◽  
Author(s):  
C. Vannier ◽  
T. L. Croxton ◽  
L. S. Farley ◽  
C. A. Hirshman
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Bay K 8644 ◽  
O2 Concentration ◽  
Voltage Dependent ◽  
Progressive Hypoxia ◽  
Carbamyl Choline

Hypoxia dilates airways in vivo and reduces active tension of airway smooth muscle in vitro. To determine whether hypoxia impairs Ca2+ entry through voltage-dependent channels (VDC), we tested the ability of dihydropyridines to modulate hypoxia-induced relaxation of KCl- and carbamyl choline (carbachol)-contracted porcine bronchi. Carbachol- or KCl-contracted bronchial rings were exposed to progressive hypoxia in the presence or absence of 1 microM BAY K 8644 (an L-type-channel agonist). In separate experiments, rings were contracted with carbachol or KCl, treated with nifedipine (a VDC antagonist), and finally exposed to hypoxia. BAY K 8644 prevented hypoxia-induced relaxation in KCl-contracted bronchi. Nifedipine (10(-5) M) totally relaxed KCl- contracted bronchi. Carbachol-contracted bronchi were only partially relaxed by nifedipine but were completely relaxed when the O2 concentration of the gas was reduced from 95 to 0%. These data indicate that hypoxia can reduce airway smooth muscle tone by limiting entry of Ca2+ through a dihydropyridine-sensitive pathway, but that other mechanisms also contribute to hypoxia-induced relaxation of carbachol-contracted bronchi.

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 Roles for RNA export factor, Nxt1, in ensuring muscle integrity and normal RNA expression in Drosophila

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kevin van der Graaf ◽  
Katia Jindrich ◽  
Robert Mitchell ◽  
Helen White-Cooper
Keyword(s):  
Mrna Export ◽  
Rna Stability ◽  
Muscle Degeneration ◽  
Loss Of Function ◽  
Cellular Functions ◽  
Partial Loss ◽  
Export Pathway ◽  
Pathway Gene ◽  
Rna Export

Abstract The mRNA export pathway is responsible for the transport of mRNAs from the nucleus to the cytoplasm, and thus is essential for protein production and normal cellular functions. A partial loss of function allele of the mRNA export factor Nxt1 in Drosophila shows reduced viability and sterility. A previous study has shown that the male fertility defect is due to a defect in transcription and RNA stability, indicating the potential for this pathway to be implicated in processes beyond the known mRNA transport function. Here we investigate the reduced viability of Nxt1 partial loss of function mutants, and describe a defect in growth and maintenance of the larval muscles, leading to muscle degeneration. RNA-seq revealed reduced expression of a set of mRNAs, particularly from genes with long introns in Nxt1 mutant carcass. We detected differential expression of circRNA, and significantly fewer distinct circRNAs expressed in the mutants. Despite the widespread defects in gene expression, muscle degeneration was rescued by increased expression of the costamere component tn (abba) in muscles. This is the first report of a role for the RNA export pathway gene Nxt1 in the maintenance of muscle integrity. Our data also links the mRNA export pathway to a specific role in the expression of mRNA and circRNA from common precursor genes, in vivo.

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 Synthesis, Characterization and Evaluation of Peptide Nanostructures for Biomedical Applications

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4587
Author(s):  
Fanny d’Orlyé ◽  
Laura Trapiella-Alfonso ◽  
Camille Lescot ◽  
Marie Pinvidic ◽  
Bich-Thuy Doan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Biomedical Applications ◽  
Chemical Reactivity ◽  
Physical Stability ◽  
Chemical Properties ◽  
Building Blocks ◽  
Imaging Probes ◽  
Therapeutic Molecules

There is a challenging need for the development of new alternative nanostructures that can allow the coupling and/or encapsulation of therapeutic/diagnostic molecules while reducing their toxicity and improving their circulation and in-vivo targeting. Among the new materials using natural building blocks, peptides have attracted significant interest because of their simple structure, relative chemical and physical stability, diversity of sequences and forms, their easy functionalization with (bio)molecules and the possibility of synthesizing them in large quantities. A number of them have the ability to self-assemble into nanotubes, -spheres, -vesicles or -rods under mild conditions, which opens up new applications in biology and nanomedicine due to their intrinsic biocompatibility and biodegradability as well as their surface chemical reactivity via amino- and carboxyl groups. In order to obtain nanostructures suitable for biomedical applications, the structure, size, shape and surface chemistry of these nanoplatforms must be optimized. These properties depend directly on the nature and sequence of the amino acids that constitute them. It is therefore essential to control the order in which the amino acids are introduced during the synthesis of short peptide chains and to evaluate their in-vitro and in-vivo physico-chemical properties before testing them for biomedical applications. This review therefore focuses on the synthesis, functionalization and characterization of peptide sequences that can self-assemble to form nanostructures. The synthesis in batch or with new continuous flow and microflow techniques will be described and compared in terms of amino acids sequence, purification processes, functionalization or encapsulation of targeting ligands, imaging probes as well as therapeutic molecules. Their chemical and biological characterization will be presented to evaluate their purity, toxicity, biocompatibility and biodistribution, and some therapeutic properties in vitro and in vivo. Finally, their main applications in the biomedical field will be presented so as to highlight their importance and advantages over classical nanostructures.

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