scholarly journals Synthesis and Preliminary Evaluation of a Novel 18F-Labeled 2-Nitroimidazole Derivative for Hypoxia Imaging

2021 ◽  
Vol 10 ◽  
Author(s):  
Jing Lu ◽  
Chi Zhang ◽  
Xi Yang ◽  
Xi-Juan Yao ◽  
Qun Zhang ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Animal Studies ◽  
Radiochemical Purity ◽  
High Sensitivity ◽  
Preliminary Evaluation ◽  
Hypoxia Imaging ◽  
Promising Candidate ◽  
Micropet Imaging ◽  
Carcinoma Tissue ◽  
Hypoxic Tumor

ObjectiveHypoxia is prevalent in tumors and plays a pivotal role in resistance to chemoradiotherapy. 18F-MISO (18F-labeled fluoromisonidazole) is currently the preferred choice of PET hypoxia tracers in clinical practice, but has severe disadvantages involving complex labeling methods and low efficient imaging due to lipophilicity. We aimed to design a novel nitroimidazole derivative labeled by 18F via a chelation technique to detect hypoxic regions and provide a basis for planning radiotherapy.Materials and MethodsFirst, we synthesized a 2-nitroimidazole precursor, 2-[4-(carboxymethyl)-7-[2-(2-(2-nitro-1H-imidazol-1-yl)acetamido)ethyl]-1,4,7-triazanonan-1-yl]acetic acid (NOTA-NI). For 18F-labeling, a 18F solution was reacted with a mixture of AlCl3 and NOTA-NI at pH 3.5 and 100°C for 20 min, and the radiochemical purity and stability were evaluated. Biological behaviors of Al18F-NOTA-NI were analyzed by an uptake study in ECA109 normoxic and hypoxic cells, and a biodistribution study and microPET imaging in ECA109 xenografted mice.ResultsAl18F-NOTA-NI required a straightforward and efficient labeling procedure compared with 18F-MISO. The uptake values were distinctly higher in hypoxic tumor cells. Animal studies revealed that the imaging agent was principally excreted via the kidneys. Due to hydrophilicity, the radioactivities in blood and muscle were decreased, and we could clearly distinguish xenografted tumors from para-carcinoma tissue by PET imaging.ConclusionsThe nitroimidazole tracer Al18F-NOTA-NI steadily accumulated in hypoxic areas in tumors and was rapidly eliminated from normal tissue. It appears to be a promising candidate for hypoxia imaging with high sensitivity and resolution.

A Preliminary Evaluation of a Prototype Western Blot Confirmatory Test Kit for Syphilis

1994 ◽  
Vol 5 (6) ◽  
pp. 409-414 ◽  
Author(s):  
H Young ◽  
P J Walker ◽  
D Merry ◽  
A Mifsud
Keyword(s):  
Western Blot ◽  
False Positive ◽  
High Sensitivity ◽  
High Specificity ◽  
Confirmatory Test ◽  
Preliminary Evaluation ◽  
Serological Tests ◽  
Western Blot Test ◽  
Specificity And Sensitivity ◽  
Test Kit

A prototype Western blot kit was evaluated as a confirmatory test for syphilis using 131 sera characterized by other serological tests for syphilis. There were 114 treponemal sera (including 94 cases of early syphilis, 83 of which were untreated) and 17 non-treponemal problem sera (11 gave false positive reactions on screening with the TmpA recombinant antigen enzyme immunoassay (EIA), 3 gave false positive fluorescent treponemal antibody absorbed (FTA-abs) tests, and 3 false positive Captia Syphilis G EIA results). Based on the manufacturer's criteria of reactivity in multiple bands for designating a positive result the Western blot test gave a sensitivity of 99.1% (113/114) and a specificity of 88.2% (15/17) when indeterminate reactions were scored positive and 98.2% (112/114) and 100% (17/17) when indeterminate reactions were scored negative. Sensitivity was high in both treated and untreated infection. Corresponding sensitivities for the TPHA and FTA-abs when equivocal reactions were scored negative were 97.5% (111/114) and 99.1% (113/114). The high sensitivity of the FTA-abs in this study is probably due to the large number of untreated primary infections. Our results with the Western blot, confirm earlier studies using ‘in-house’ test systems and, support a role for a commercial Western blot test in the confirmatory diagnosis of syphilis. Further studies are required to confirm the high specificity and sensitivity of the kit in a larger series including a wider variety of non-treponemal cases as well as patients with untreated and treated infection.

NiFe/INSULATOR/Cu COMPOSITE WIRES AND THEIR GIANT MAGNETO-IMPEDANCE EFFECTS

2010 ◽  
Vol 17 (03) ◽  
pp. 369-373 ◽  
Author(s):  
N. NING ◽  
J. FAN ◽  
J. WU ◽  
H. CHIRIAC ◽  
X. P. LI
Keyword(s):  
Seed Layer ◽  
Copper Wire ◽  
Magnetic Layer ◽  
High Sensitivity ◽  
Composite Wire ◽  
Sensing Element ◽  
Promising Candidate ◽  
Insulator Layer ◽  
Giant Magneto Impedance ◽  
Composite Wires

In this work, two types of electrodeposited Ni–Fe /insulator/ Cu composite wires, namely Ni–Fe /seed layer/glass coated copper wire (Composite Wire A), and Ni–Fe /seed layer/sputtered SiO2/Cu (Composite Wire B), have been fabricated and their giant magneto-impedance effects have been investigated. With different implementations of the insulator layer, the magneto-impedance effect of Composite Wire A, whose insulator layer is cast from the melt Pyrex, is significantly higher than that of Composite Wire B with an insulator of sputtered SiO 2 layer. The profile of the insulator layer, as well as the thickness of magnetic layer and the diameter of the conductive core, greatly influences the interaction between the magnetic layer of Ni–Fe and the copper core, as shown in their giant magneto-impedance (GMI) effects. The maximum MI ratios obtained from Composite Wires A and B are 226% at 800 kHz when H ext = 0.87 Oe , and 95% at 1 MHz when H ext = 0 Oe , respectively. The Composite Wire A is a promising candidate for the sensing element of high sensitivity sensors to very weak magnetic field. For Composite Wire B, further improvement on its GMI effect and sensing performance requires optimization of its geometric parameters and the deposition conditions.

Identification and expression distribution of esophageal carcinoma autoantigens.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16520-e16520
Author(s):  
Fuchun Si
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Esophageal Carcinoma ◽  
Normal Tissue ◽  
Proteome Analysis ◽  
Tumor Rejection ◽  
Cancer Tissue ◽  
Carcinoma Tissue ◽  
Heat Shock Protein Gp96 ◽  
Tumor Rejection Antigen

e16520 Background: To identify the autoantigen protein molecules with autoserum in the tissues from the esophageal carcinoma (EC) patients, analyze autoantigen expression distribution in EC tissues, so as to provide basis for the molecular pathogenesis and clinical medication of EC. Methods: 69 cases of EC patients tissues and serum and 81 cases of healthy people serum were collected, serological proteome analysis (SERPA) was modified with sequential extraction of subcellular protein fractions to identify esophageal oncopathgensis stages autoantigen with autoserum in the tissues from the EC patients. Another 93 cases of EC patients tissue were collected, immunohistochemical and western blot method were used to detect expression distribution of EC autoantigens in esophageal carcinoma tissue, para-carcinoma tissue and normal tissue. Results: Autoantigens CK13, CK16, CaD, ACTG2, tumor rejection antigen (gp96) 1 variant, heat shock protein gp96 precursor were identified, among wihich, CK16, CaD, ACTG2, tumor rejection antigen (gp96)1 variant, heat shock protein gp96 precursor were firstly reported as EC autoantigens. Expression of autoantigens CK16, CaD, ACTG2 were increased in EC carcinoma tissue than para-carcinoma tissue and normal tissue, while CK13 were decreased. Positive expression level of CK16 in normal tissue, para-carcinoma tissue and cancer tissue of EC patients was 0.0076±0.0033, 0.0158±0.0065, 0.0356±0.0165 respectively, CaD was 0.0085±0.0048, 0.0107±0.0056, 0.0177±0.0103 respectively, ACTG2 was 0.0091±0.0039, 0.0136±0.0043, 0.0214±0.0110 respectively, and CK13 was 0.2053±0.0311, 0.1633±0.0280, 0.0412±0.0239 respectively. Conclusions: 6 EC autoantigens were identified, and 5 were first reported. Autoantigens CK13, CK16, CaD and ACTG2 were expressed in EC patients carcinoma tissue, which can be the potential biomarkers of esophageal carcinoma. This study provides new basis for the EC molecular mechanism and development of molecular drugs.

Monolayer Ti2CO2: A Promising Candidate for NH3 Sensor or Capturer with High Sensitivity and Selectivity

2015 ◽  
Vol 7 (24) ◽  
pp. 13707-13713 ◽  
Author(s):  
Xue-fang Yu ◽  
Yan-chun Li ◽  
Jian-bo Cheng ◽  
Zhen-bo Liu ◽  
Qing-zhong Li ◽  
...  
Keyword(s):  
High Sensitivity ◽  
Promising Candidate ◽  
Sensitivity And Selectivity ◽  
Nh3 Sensor

Direct evidence that prostate tumors show high sensitivity to fractionation (low α/β ratio), similar to late-responding normal tissue

2002 ◽  
Vol 52 (1) ◽  
pp. 6-13 ◽  
Author(s):  
David J Brenner ◽  
Alvaro A Martinez ◽  
Gregory K Edmundson ◽  
Christina Mitchell ◽  
Howard D Thames ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Direct Evidence ◽  
High Sensitivity ◽  
Prostate Tumors

scholarly journals Carbon Nitride Nanotube as a Chemical Sensor for Melamine: A Theoretical Study

2017 ◽  
Vol 60 (4) ◽  
Author(s):  
Reza Moradi ◽  
Javad Hosseini Hosseini
Keyword(s):  
Density Functional ◽  
Carbon Nitride ◽  
Adsorption Process ◽  
Chemical Sensor ◽  
Theoretical Study ◽  
Tube Wall ◽  
High Sensitivity ◽  
Tube Surface ◽  
Promising Candidate ◽  
Short Recovery Time

The interaction of a melamine molecule with a carbon nitride nanotube (CNNT) was explored by means of dispersion-corrected density functional calculations. It was found that melamine prefers to be adsorbed on the porous site of the tube wall with the adsorption energy of -21.9 kcal/mol. This adsorption process significantly shifts the HOMO of the tube to higher energies, thereby reducing the gap of the tube from 3.97 to 2.65 eV. Moreover, the work function is slightly decreased which can facilitate the field electron emission from the tube surface. It is expected that CNNT can be a promising candidate for sensor devices in detecting the melamine molecule with short recovery time and high sensitivity.

scholarly journals Targeted and Non-Targeted Mechanisms for Killing Hypoxic Tumour Cells—Are There New Avenues for Treatment?

2021 ◽  
Vol 22 (16) ◽  
pp. 8651
Author(s):  
Alyssa Gabrielle Apilan ◽  
Carmel Mothersill
Keyword(s):  
Normal Tissue ◽  
Drug Delivery Systems ◽  
Mechanisms Of Action ◽  
Tumour Cells ◽  
Cell Manipulation ◽  
Tumour Hypoxia ◽  
Compelling Evidence ◽  
Relative Resistance ◽  
Hypoxia Imaging ◽  
Normal Tissues

Purpose: A major issue in radiotherapy is the relative resistance of hypoxic cells to radiation. Historic approaches to this problem include the use of oxygen mimetic compounds to sensitize tumour cells, which were unsuccessful. This review looks at modern approaches aimed at increasing the efficacy of targeting and radiosensitizing hypoxic tumour microenvironments relative to normal tissues and asks the question of whether non-targeted effects in radiobiology may provide a new “target”. Novel techniques involve the integration of recent technological advancements such as nanotechnology, cell manipulation, and medical imaging. Particularly, the major areas of research discussed in this review include tumour hypoxia imaging through PET imaging to guide carbogen breathing, gold nanoparticles, macrophage-mediated drug delivery systems used for hypoxia-activate prodrugs, and autophagy inhibitors. Furthermore, this review outlines several features of these methods, including the mechanisms of action to induce radiosensitization, the increased accuracy in targeting hypoxic tumour microenvironments relative to normal tissue, preclinical/clinical trials, and future considerations. Conclusions: This review suggests that the four novel tumour hypoxia therapeutics demonstrate compelling evidence that these techniques can serve as powerful tools to increase targeting efficacy and radiosensitizing hypoxic tumour microenvironments relative to normal tissue. Each technique uses a different way to manipulate the therapeutic ratio, which we have labelled “oxygenate, target, use, and digest”. In addition, by focusing on emerging non-targeted and out-of-field effects, new umbrella targets are identified, which instead of sensitizing hypoxic cells, seek to reduce the radiosensitivity of normal tissues.

Cancer Imaging with CEA Antibodies: Historical and Current Perspectives

1992 ◽  
Vol 7 (3) ◽  
pp. 183-188 ◽  
Author(s):  
D.M. Goldenberg
Keyword(s):  
Monoclonal Antibody ◽  
Animal Studies ◽  
Clinical Success ◽  
Cancer Imaging ◽  
High Sensitivity ◽  
Antibody Fragments ◽  
Igg Antibodies ◽  
Fab Fragment ◽  
Dual Isotope ◽  
Radiolabeled Antibodies

This article reviews the history and status of cancer imaging with radiolabeled antibodies against carcinoembryonic antigen (CEA). Although CEA and many other cancer-associated antigens are not distinct for neoplasia, the quantitative increase of these markers in malignant tissues provides a sufficient differential for selective antibody targeting. Animal studies with xenografted human tumors provided the first evidence of the prospects of this technology, followed by initial clinical success with purified goat whole IgG antibodies to CEA, labeled with 131I and with the use of dual-isotope subtraction methods. Subsequently, improved and earlier imaging could be accomplished with monoclonal antibody fragments, which then would permit the use of shorter-lived radionuclides, such as 111In, 123I, and 99mTc. The preferred use of a monoclonal anti-CEA IgG Fab' fragment, labeled with 99mTc by a recently developed, simple and rapid kit, has enabled the detection of small lesions, including those in the liver, within 4 h of injection. By means of SPECT imaging, a high sensitivity and specificity for RAID could be achieved.

Preparation and Preliminary Evaluation of 68 Ga-Acridine: An Attempt to Study the Potential of Radiolabeled DNA Intercalator as a PET Radiotracer for Tumor Imaging

2020 ◽  
Vol 20 (13) ◽  
pp. 1538-1547 ◽  
Author(s):  
Subhajit Ghosh ◽  
Tapas Das ◽  
Shishu K. Suman ◽  
Haladhar D. Sarma ◽  
Ashutosh Dash
Keyword(s):  
Radiochemical Purity ◽  
Tumor Imaging ◽  
Raji Cell ◽  
Biological Behavior ◽  
Preliminary Evaluation ◽  
Dna Intercalator ◽  
Tumor Accumulation ◽  
The Stability

Introduction: Acridine is a well-known DNA intercalator and thereby gets easily inserted within DNA. As uncontrolled rapid cell division is one of the primary characteristics of the tumors, it is expected that acridine or its suitable derivatives will have preferential accumulation in the tumorous lesions. Therefore, an attempt was made to radiolabel an acridine derivative with 68Ga and study the potential of the 68Ga-acridine complex as a PET agent for tumor imaging. Methods: 9-aminoacridine was coupled with p-NCS-benzyl-DOTA to render it suitable for labeling with 68Ga. The purified acridine-DOTA conjugate was radiolabeled with 68Ga, eluted from a 68Ge/68Ga radionuclide generator. Various radiolabeling parameters were optimized and the stability of the radiolabeled preparation was studied. The biological behavior of the 68Ga-acridine complex was studied both in vitro and in vivo using Raji cell line and fibrosarcoma tumor bearing Swiss mice, respectively. Results: 68Ga-acridine complex was obtained with ~100% radiochemical purity under the optimized reaction conditions involving incubation of 2mg/mL of ligand at 100°C for 30 minutes. The complex maintained a radiochemical purity of >95% in normal saline and >65% in human blood serum at 3h post-incubation. In vitro cellular study showed (3.2±0.1)% uptake of the radiotracer in the Raji cells. Biodistribution study revealed significant tumor accumulation [(11.41±0.41)% injected activity in per gram] of the radiotracer within 1h postadministration along with uptake in other non-target organs such as, blood, liver, GIT kidney etc. Conclusion: The present study indicates the potential of 68Ga-acridine as a PET agent for imaging of tumorous lesions. However, further detailed evaluation of the agent is warranted to explore its actual potential.

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