scholarly journals Radiolabeled Cationic Peptides for Targeted Imaging of Infection

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Tolulope A. Aweda ◽  
Zumrut F. B. Muftuler ◽  
Adriana V. F. Massicano ◽  
Dhruval Gadhia ◽  
Kelly A. McCarthy ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Membrane Lipids ◽  
Molecular Probes ◽  
Unnatural Amino Acid ◽  
Control Group ◽  
Post Injection ◽  
Bacterial Membranes ◽  
Biodistribution Studies ◽  
Infected Muscle

Molecular probes targeting bacteria provide opportunities to target bacterial infections in vivo for both imaging and therapy. In the current study, we report the development of positron emission tomography (PET) probes for imaging of live bacterial infection based on the small molecules HLys-DOTA, a polycationic peptide synthesized as the D-isomer (RYWVAWRNRG) conjugated to 1, 4, 7, 10-tetraazacyclododecane-N′,N″,N‴,N-tetraacetic acid (DOTA) and AB1-HLys-DOTA, which includes an unnatural amino acid AB1 that preferentially binds to bacteria membrane lipids with amine groups via formation of iminoboronates. HLys-DOTA and AB1-HLys-DOTA peptides were radiolabeled with 64Cu and investigated as PET imaging agents to track bacterial infection in vitro and in intramuscularly infected (IM) mice models. Cell uptake studies at 37°C in Staphylococcus aureus (SA) show higher uptake of 64Cu-AB1-HLys-DOTA; 98.47 ± 3.54% vs 64Cu-HLys-DOTA; 39.12 ± 3.27% at 24 h. Standard uptake values (SUV) analysis of the PET images resulted in mean SUV of 0.70 ± 0.08, 0.49 ± 0.04, and 0.31 ± 0.01 for 64Cu-AB1-HLys-DOTA and 0.17 ± 0.06, 0.16 ± 0.02, and 0.13 ± 0.01 for 64Cu-HLys-DOTA at 1, 4, and 24 h post injection, respectively, in the infected muscles. Similarly, in the biodistribution studies, dose uptake in the infected muscles was 4 times higher in the targeted 64Cu-AB1-HLys-DOTA group than in the 64Cu-HLys-DOTA group and 2‐3 times higher than in the PBS control group at 1, 4, and 24 h post injection. 64Cu-AB1-HLys-DOTA was able to distinguish between SA-infected muscle and Pseudomonas aeruginosa (PA) infected muscle with lower mean SUV of 0.28 ± 0.10 at 1 h post injection. This illustrates the utility of the AB1 covalently targeting group in synergy with the HLys peptide, which noncovalently binds to bacterial membranes. These results suggest that 64Cu-labeled AB1-HLys-DOTA peptide could be used as an imaging probe for detection of bacterial infection in vivo with specificity for Gram-positive bacteria.

Radioiodination and biological evaluation of Cimetidine as a new highly selective radiotracer for peptic ulcer disorder detection

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Mahmoud H. Sanad ◽  
Safaa B. Challan ◽  
Fawzy A. Marzook ◽  
Sayed M. Abd-Elhaliem ◽  
Ebtisam A. Marzook
Keyword(s):  
Peptic Ulcer ◽  
Nuclear Imaging ◽  
Radiochemical Yield ◽  
Biological Evaluation ◽  
Stomach Ulcer ◽  
Control Group ◽  
Factors Affecting ◽  
Biodistribution Studies

AbstractOne of the most famous techniques for stomach ulcer imaging is the nuclear imaging technique. We aim to focus on the synthesis of 125I-cimetidine (125I-cim) as an agent for peptic ulcer imaging. Cimetidine was labeled with Iodine-125 using a different oxidizing agent (Ch-T, NBS). All factors affecting the labeling yield were optimized. The radiochemical yield of 125I-cim was 98 ± 0.22% at optimum conditions. In vitro stability, in vivo biodistribution of 125I-cimetidine was studied in three groups: control group, pretreated group, and ulcer bearing group. In vivo biodistribution studies of 125I-cim revealed high uptake in the stomach ulcer, reaching about 75.4 ± 1.2% ID/g at 15 min post-injection, than pretreated groups compared to the control. The results showed the suitability of using 125I-cimetidine for stomach ulcer imaging.

Bifunctional HPPH-N2S2-99mTc conjugates as tumor imaging agents: synthesis and biodistribution studies

2003 ◽  
Vol 07 (07) ◽  
pp. 500-507 ◽  
Author(s):  
Bing Ma ◽  
Guolin Li ◽  
Peter Kanter ◽  
Dominick Lamonica ◽  
Zachary Grossman ◽  
...  
Keyword(s):  
Half Life ◽  
Tumor Imaging ◽  
Post Injection ◽  
Tumor Uptake ◽  
In Vivo Biodistribution ◽  
Structure Activity ◽  
Biodistribution Studies ◽  
Activity Screening ◽  
Pyropheophorbide A

Pyropheophorbide-a and the corresponding 3-(1'-hexyloxyethyl)-3-devinyl derivative ( HPPH ), the tumor-avid photosensitizers were conjugated with mono- or di-bisaminoethanethiols ( N 2 S 2 ligand). The in vivo biodistribution study of the related 99m Tc complexes was performed in F-344 rats bearing Ward colon tumors at 4 h and 24 h post injection. These data show that the complexes are stable and among four tracers, HPPH di-99 m Tc N 2 S 2 conjugate reaches the highest tumor uptake (%ID/g). The larger tumors reach higher concentrations of the tracer. However, the short 6 h half life of 99 m Tc is incompatible with the 24 h imaging time, suggesting that the use of a longer-lived isotope such as 111 In could still provide a useful scanning agent, or that further structure-activity screening could yield an HPPH analog with more appropriate pharmacokinetics for tumor imaging with 99 m Tc .

Isoflavone-Rich Soy Isolate Reduces Lipid Peroxidation in Mouse Liver

2008 ◽  
Vol 78 (45) ◽  
pp. 217-222 ◽  
Author(s):  
Wissam H. Ibrahim ◽  
Hosam M. Habib ◽  
Ching K. Chow ◽  
Geza G. Bruckner
Keyword(s):  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Glutathione Peroxidase ◽  
Membrane Lipids ◽  
Basal Diet ◽  
Conjugated Dienes ◽  
Control Group ◽  
Peroxidative Damage ◽  
Soy Isolate

The purpose of this study was to determine if an isoflavone-rich soy isolate affords protection against peroxidative damage in vivo. Weanling C57BL6 male mice were fed a basal diet (AIN-93G) supplemented with either nothing or 1.08 gram isoflavone-rich soy isolate/kg diet for 60 days. The soy isolate contained 400 mg/g isoflavone aglycones (226 mg/g genistein and 174 mg/g daidzein). Immediately following sacrifice liver was processed for measuring the levels of lipid peroxidation products, malondialdehyde (MDA) and conjugated dienes, and the levels of α-tocopherol, glutathione (GSH), and ascorbic acid, as well as the activities of catalase, selenium-dependent glutathione peroxidase (Se-GPx), selenium-nondependent glutathione peroxidase (non-Se-GPx), and superoxide dismutase (SOD). Compared with the control group, mice fed the diet supplemented with soy isolate had significantly (p < 0.05) lower hepatic levels of MDA and conjugated dienes. The activities of catalase and SOD were significantly increased (p < 0.05) in the liver of soy isolate-supplemented mice. The levels of vitamin E, GSH, and ascorbic acid and the activities of Se-GPx and non-Se-GPx were not significantly altered by the soy isolate. The results obtained provide experimental evidence that isoflavone supplementation confers protection against peroxidative damage to membrane lipids in vivo, possibly through enhancing the activities of the antioxidant enzymes catalase and SOD.

scholarly journals Synthesis, radiolabelling, and biodistribution studies of triazole derivatives for targeting melanoma

2016 ◽  
Vol 94 (9) ◽  
pp. 773-780 ◽  
Author(s):  
Stephanie M. Rathmann ◽  
Nancy Janzen ◽  
John F. Valliant
Keyword(s):  
Computed Tomography ◽  
Single Photon ◽  
Click Reaction ◽  
Photon Emission ◽  
Molecular Probes ◽  
High Signal ◽  
Emission Computed Tomography ◽  
In Vivo Evaluation ◽  
Biodistribution Studies

Molecular probes that target specific markers expressed in solid tumours are in demand for cancer imaging and radionuclide therapy applications. The synthesis, characterization, and in vivo evaluation of radioiodinated triazoles designed as probes to target melanoma are described here. Compounds were prepared using a thermal click reaction between ethynylstannane and methyl 2-azidoacetate, resulting in preferential formation of the corresponding 1,4-tin triazole. The primary amine of various targeting vectors was then coupled to the resulting tin triazole methyl ester. These precursors were labelled with no carrier added 123I or 125I and purified by high performance liquid chromatography to give isolated radiochemical yields between 6% and 51% and radiochemical purities of >95% in all cases. Among the evaluated compounds, N-(2-diethylamino-ethyl)-2-(4-iodo-[1,2,3]triazol-1-yl)acetamide (7a) and N-(1-benzylpiperidin-4-yl)-2-(4-iodo-1H-1,2,3-triazol-1-yl)acetamide (7d) showed the most promising in vivo data, and their 123I-labelled forms were used in single photon emission computed tomography computed tomography (SPECT–CT) imaging studies. The imaging data showed excellent tumour visualization with a very high signal to noise ratio.

scholarly journals CMKLR1-targeting peptide tracers for PET/MR imaging of breast cancer

2019 ◽  
Author(s):  
Sarah Erdmann ◽  
Lars Niederstadt ◽  
Eva Jolanthe Koziolek ◽  
Juan Daniel Castillo Gómez ◽  
Sonal Prasad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mr Imaging ◽  
Ex Vivo ◽  
Xenograft Model ◽  
Organ Distribution ◽  
Post Injection ◽  
Tumor Uptake ◽  
Biodistribution Studies ◽  
Targeting Peptide

AbstractMolecular targeting remains to be a promising approach in cancer medicine. Knowledge about molecular properties such as overexpression of G protein-coupled receptors (GPCRs) is thereby offering a powerful tool for tumor-selective imaging and treatment of cancer cells. We utilized chemerin-based peptides for CMKLR1 receptor targeting in a breast cancer xenograft model. By conjugation with radiolabeled chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), we obtained a family of highly specific and affine tracers for hybridin vivoimaging with positron emission tomography (PET)/ magnetic resonance (MR) and concomitant biodistribution studies.MethodsWe developed five highly specific and affine peptide tracers targeting CMKLR1 by linker-based conjugation of chemerin peptide analogs (CG34 and CG36) with radiolabeled (68Ga) chelator DOTA. Our established xenograft model with target-positive DU4475 and negative A549 tumors in immunodeficient nude mice enabled CMKLR1-specific imagingin vivo. Therefore, we acquired small animal PET/MR images, assessed biodistribution byex vivomeasurements and investigated the tracer specificity by blocking experiments.ResultsThe family of five CMKLR1-targeting peptide tracers demonstrated high biological activity and affinityin vitrowith EC50and IC50values being below 2 nM. Our target-positive (DU4475) and target-negative (A549) xenograft model could be confirmed byex vivoanalysis of CMKLR1 expression and binding. After preliminary PET imaging, the three most promising tracers68Ga-DOTA-AHX-CG34,68Ga-DOTA-KCap-CG34 and68Ga-DOTA-ADX-CG34 with apparent DU4475 tumor uptake were further analyzed. Hybrid PET/MR imaging along with concomitant biodistribution studies revealed distinct CMKLR1-specific uptake (5.1% IA/g, 4.5% IA/g and 6.2% IA/g 1 h post-injection) of our targeted tracers in DU4475 tumor tissue. More strikingly, the tumor uptake could be blocked by excess of unlabeled peptide (6.4-fold, 7.2-fold and 3.4-fold 1 h post-injection) and further confirmed the CMKLR1 specificity. As our five tracers, each with particular degree of hydrophobicity, showed different results regarding tumor uptake and organ distribution, we identified these three tracers with moderate, balanced properties to be the most potent in receptor-mediated tumor targeting.ConclusionWith the breast cancer cell line DU4475, we established a model endogenously expressing our target CMKLR1 to evaluate our chemerin-based peptide tracers as highly affine and specific targeting agents. Eventually, we demonstrated the applicability of our68Ga-labeled tracers by visualizing CMKLR1-positive breast cancer xenografts in PET/MR imaging and thus developed promising theranostics for tumor treatment.

scholarly journals Distinct functional roles for hopanoid composition in the chemical tolerance ofZymomonas mobilis

2018 ◽  
Author(s):  
Léa Brenac ◽  
Edward E.K. Baidoo ◽  
Jay D. Keasling ◽  
Itay Budin
Keyword(s):  
Group Composition ◽  
Membrane Lipids ◽  
Head Group ◽  
Polar Group ◽  
Measured Concentration ◽  
Growth And Survival ◽  
Functional Roles ◽  
Bacterial Membranes ◽  
Transposon Mutants

SummaryHopanoids are abundant membrane lipids found in diverse bacterial lineages, but their physiological roles are not well understood. The ethanol fermenterZymomonas mobilisfeatures the highest measured concentration of hopanoids, leading to the hypothesis that these lipids can protect against bacterial solvent toxicity. However, the lack of genetic tools for manipulating hopanoid compositionin vivohas limited their further functional analysis. Because of polyploidy (> 50 genome copies per cell), we found that disruptions of essential hopanoid biosynthesis (hpn) genes inZ. mobilisact as genetic knockdowns, reliably modulating the abundance of different hopanoid species. Using a set ofhpntransposon mutants, we demonstrate that both reduced hopanoid content and modified hopanoid head group composition mediate growth and survival in ethanol. In contrast, the amount of hopanoids, but not their polar group composition, contributes to fitness at low pH. Spectroscopic analysis of model membranes showed that hopanoids protect against several ethanol-driven phase transitions in membrane structure, including lipid interdigitation and bilayer dissolution. We propose that hopanoids act through a combination of hydrophobic and inter-lipid hydrogen bonding interactions to stabilize bacterial membranes against solvent stress.Graphical abstract

Facilitated migration of cells from a transected peripheral nerve over collagen fibers: in vivo observations

1989 ◽  
Vol 47 ◽  
pp. 888-889
Author(s):  
Arthur J. Wasserman ◽  
Azam Rizvi ◽  
George Zazanis ◽  
Frederick H. Silver
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Collagen Gel ◽  
Collagen Fibers ◽  
Control Group ◽  
Guide Tube ◽  
Sprague Dawley ◽  
Silicone Tube ◽  
Thin Sections

In cases of peripheral nerve damage the gap between proximal and distal stumps can be closed by suturing the ends together, using a nerve graft, or by nerve tubulization. Suturing allows regeneration but does not prevent formation of painful neuromas which adhere to adjacent tissues. Autografts are not reported to be as good as tubulization and require a second surgical site with additional risks and complications. Tubulization involves implanting a nerve guide tube that will provide a stable environment for axon proliferation while simultaneously preventing formation of fibrous scar tissue. Supplementing tubes with a collagen gel or collagen plus extracellular matrix factors is reported to increase axon proliferation when compared to controls. But there is no information regarding the use of collagen fibers to guide nerve cell migration through a tube. This communication reports ultrastructural observations on rat sciatic nerve regeneration through a silicone nerve stent containing crosslinked collagen fibers.Collagen fibers were prepared as described previously. The fibers were threaded through a silicone tube to form a central plug. One cm segments of sciatic nerve were excised from Sprague Dawley rats. A control group of rats received a silicone tube implant without collagen while an experimental group received the silicone tube containing a collagen fiber plug. At 4 and 6 weeks postoperatively, the implants were removed and fixed in 2.5% glutaraldehyde buffered by 0.1 M cacodylate containing 1.5 mM CaCl2 and balanced by 0.1 M sucrose. The explants were post-fixed in 1% OSO4, block stained in 1% uranyl acetate, dehydrated and embedded in Epon. Axons were counted on montages prepared at a total magnification of 1700x. Montages were viewed through a dissecting microscope. Thin sections were sampled from the proximal, middle and distal regions of regenerating sciatic plugs.

In-vitro- und In-vivo-Wirkung von Schilddrüsenhormon auf das Wachstum von Neuroblastomzellen

1990 ◽  
Vol 29 (03) ◽  
pp. 120-124
Author(s):  
R. P. Baum ◽  
E. Rohrbach ◽  
G. Hör ◽  
B. Kornhuber ◽  
E. Busse
Keyword(s):  
Cell Differentiation ◽  
Neuroblastoma Cells ◽  
Control Group ◽  
Initial Value ◽  
Initial Rise ◽  
Biphasic Effect ◽  
Contrast Microscopy ◽  
Morphological Sign

The effect of triiodothyronine (T3) on the differentiation of cultured neuroblastoma (NB) cells was studied after 9 days of treatment with a dose of 10-4 M/106 cells per day. Using phase contrast microscopy, 30-50% of NB cells showed formation of neurites as a morphological sign of cellular differentiation. The initial rise of the mitosis rate was followed by a plateau. Changes in cyclic nucleotide content, in the triphosphates and in the activity of the enzyme ornithine decarboxylase (ODC) were assessed in 2 human and 2 murine cell lines to serve as biochemical parameters of the cell differentiation induced by T3. Whereas the cAMP level increased significantly (3 to 7 fold compared with its initial value), the cGMP value dropped to 30 to 50% of that of the control group. ATP and GTP increased about 200%, the ODC showed a decrease of about 50%. The present studies show a biphasic effect of T3 on neuroblastoma cells: the initial rise of mitotic activity is followed by increased cell differentiation starting from day 4 of the treatment.

Platelet Aggregation in Diabetes Mellitus and the Effect of Insulin in Vivo on Aggregation

1972 ◽  
Vol 27 (01) ◽  
pp. 114-120 ◽  
Author(s):  
A. A Hassanein ◽  
Th. A El-Garf ◽  
Z El-Baz
Keyword(s):  
Platelet Aggregation ◽  
Rapid Onset ◽  
Control Group ◽  
Diabetic Patients ◽  
Fasting State ◽  
Clotting Time ◽  
Cholesterol Levels ◽  
Platelet Disaggregation ◽  
Aggregation And Disaggregation

SummaryADP-induced platelet aggregation and calcium-induced platelet aggregation tests were studied in 14 diabetic patients in the fasting state and half an hour after an intravenous injection of 0.1 unit insulin/kg body weight. Platelet disaggregation was significantly diminished as compared to a normal control group, and their results were negatively correlated with the corresponding serum cholesterol levels. Insulin caused significant diminution in the ADP-induced platelet aggregation as a result of rapid onset of aggregation and disaggregation. There was also a significant increase in platelet disaggregation. In the calcium-induced platelet aggregation test, there was a significant shortening of the aggregation time, its duration, and the clotting time. The optical density fall due to platelet aggregation showed a significant increase. Insulin may have a role in correcting platelet disaggregation possibly through improvement in the intracellular enzymatic activity.

Consumption of Hageman Factor Activity in the Generalized Shwartzman Reaction Induced by Liquoid

1970 ◽  
Vol 23 (02) ◽  
pp. 386-404 ◽  
Author(s):  
G Müller-Berghaus ◽  
H. G Lasch
Keyword(s):  
Partial Thromboplastin Time ◽  
Lethal Dose ◽  
Control Group ◽  
Factor V ◽  
Consumption Coagulopathy ◽  
Factor Activity ◽  
Hageman Factor ◽  
Intravascular Coagulation ◽  
Shwartzman Reaction

SummaryThe role of Hageman factor in triggering intravascular coagulation has been studied in rabbits injected intravenously with Liquoid. Besides changes of coagulation parameters characteristic of consumption coagulopathy (e.g. decrease in platelet counts, fibrinogen levels, factor V activity), a pronounced drop in Hageman factor activity was observed after injection of Liquoid. Likewise, the partial thromboplastin time became prolonged.The activation of Hageman factor in vivo could be prevented by intravenous infusion of lysozyme. Twenty min after starting the lysozyme infusion, the partial thromboplastin time became prolonged from a mean of 29 sec to 108 sec. Animals infused with lysozyme and injected with a lethal dose of Liquoid did not develop a consumption coagulopathy. In the same manner, none of 10 animals treated with lysozyme developed the generalized Shwartzman reaction, whereas in the control group 19 out of 20 animals showed fibrin thrombi in the glomerular capillaries.From the present study it may be concluded that the intravascular coagulation process after intravenous injection of Liquoid is triggered by Hageman factor activation.

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