99mTc-HYNIC-TOC imaging in the evaluation of pancreatic masses which are potential neuroendocrine tumors.

PubMed

Qiao, Zhen; Zhang, Jingjing; Jin, Xiaona; Huo, Li; Zhu, Zhaohui; Xing, Haiqun; Li, Fang

2015-05-01

The aim of this investigation was to determine the accuracy of the findings and the diagnoses of Tc-hydrazinonicotinyl-Tyr3-octreotide scan (Tc-HYNIC-TOC imaging) in patients with pancreatic masses which were potential neuroendocrine tumors. Records of total 20 patients with pancreatic masses were retrospectively reviewed. All of the patients had been revealed by abdominal contrast CT and possibility of neuroendocrine tumors could not be excluded by CT imaging before Tc-HYNIC-TOC imaging. Tc-HYNIC-TOC imaging was performed at 1 and 4 hours post-tracer injection, and SPECT/CT images of the abdomen were also acquired. The image findings were compared to final diagnoses which were made from pathological examination. Among all 20 pancreatic masses evaluated, there were 16 malignant lesions which included 1 ductal adenocarcinoma and 15 neuroendocrine tumors. Tc-HYNIC-TOC imaging identified 14 of 15 pancreatic neuroendocrine tumors and excluded 4 of 5 lesions which were not neuroendocrine tumors. The overall sensitivity, specificity, and accuracy was therefore 93.3% (14 of 15), 80% (4 of 5), and 90.0% (18 of 20), respectively, in our patient population. Tc-HYNIC-TOC imaging provides reasonable accuracy in the evaluation pancreatic mass suspected to be neuroendocrine tumors.

99mTc-EDDA/HYNIC-octreotate scintigraphy, an efficient method for the detection and staging of carcinoid tumours: results of 3 years' experience.

PubMed

Hubalewska-Dydejczyk, A; Fröss-Baron, K; Mikołajczak, R; Maecke, H R; Huszno, B; Pach, D; Sowa-Staszczak, A; Janota, B; Szybiński, P; Kulig, J

2006-10-01

At all stages of the disease, serious difficulties are encountered in the imaging diagnosis of carcinoids. Somatostatin receptor scintigraphy (SRS) holds great promise for detecting primary tumours and metastases. 99mTc-EDDA/HYNIC-octreotate should significantly improve the diagnosis of carcinoids in comparison with 111In-Octreoscan owing to the better affinity for SSR2 and the higher count rate. The aim of this study was to assess the diagnostic efficiency of 99mTc-EDDA/HYNIC-octreotate scintigraphy in the detection and staging of carcinoid tumours. The study population comprised 75 patients (age 48.5+/-15.5 years): 46 with histological confirmation of carcinoid and 29 with suspected disease. 99mTc-EDDA/HYNIC-octreotate (740 MBq) SRS and CT were performed in all patients. Fifteen patients were examined with 111In-Octreoscan. High-quality 99mTc-EDDA/HYNIC-octreotate images were obtained in all cases, with maximum tumour tracer accumulation 4 h p.i. The mean target/non-target ratios for whole body (WB) and SPECT scans were, respectively, as follows: primary lesions: 4.5 and 10.2; metastases: liver, 3.1 and 12.3; abdominal focal lesions, 2.7 and 5.8; lung, 2.7 and 8.3; mediastinum, 3.4 and 7.6; bones, 6.8 and 19.0. 99mTc-EDDA/HYNIC-octreotate WB scans revealed more metastases than 111In-Octreoscan, with better individual separation. 99mTc-EDDA/HYNIC-octreotate SRS revealed new metastatic lesions in seven patients with confirmed carcinoid, and in four with dissemination the primary focus was found. Five patients qualified for radioguided surgery and 11 were referred to 90Y-DOTA-TATE therapy. The sensitivity of SRS in comparison with CT was higher for primary lesions and liver and abdominal lymph node metastases. In the subgroup of patients with suspected neuroendocrine tumours, two duodenal carcinoids, one thymic carcinoid and one ileal carcinoid were found. 99mTc-EDDA/HYNIC-octreotate, with high imaging quality, is an excellent alternative to 111In-Octreoscan for

99mTc-HYNIC-TOC scintigraphy is superior to 131I-MIBG imaging in the evaluation of extraadrenal pheochromocytoma.

PubMed

Chen, Libo; Li, Fang; Zhuang, Hongming; Jing, Hongli; Du, Yanrong; Zeng, Zhengpei

2009-03-01

In this investigation, the efficacy of scintigraphy using (99m)Tc-labeled hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC) in the evaluation of extraadrenal pheochromocytoma was assessed and compared with (131)I-labeled metaiodobenzylguanidine (MIBG) imaging. Ninety-seven patients who were suspected of having pheochromocytoma but showed no definite adrenal abnormalities on CT were evaluated by both (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging. The results were compared with pathology findings or clinical follow-up. Of 58 patients proven to be without pheochromocytoma, (99m)Tc-HYNIC-TOC and (131)I-MIBG imaging excluded 56 and 58 patients, respectively, rendering a specificity of 96.6% for (99m)Tc-HYNIC-TOC imaging and 100% for (131)I-MIBG imaging. In the evaluation of adrenal pheochromocytoma (14 patients), the sensitivity of (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging was 50% and 85.7%, respectively. However, in the evaluation of extraadrenal pheochromocytomas (25 patients), the sensitivity of (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging was 96.0% and 72.0%, respectively. (99m)Tc-HYNIC-TOC scintigraphy is more sensitive than (131)I-MIBG imaging in the detection of extraadrenal pheochromocytomas.

Limitations and pitfalls of 99mTc-EDDA/HYNIC-TOC (Tektrotyd) scintigraphy.

PubMed

Garai, Ildikó; Barna, Sandor; Nagy, Gabor; Forgacs, Attila

2016-01-01

Tektrotyd kit was developed by Polatom company for 99mTc labeling to make an alternative tracer of somatostatin receptor scintigraphy available. Since 2005, 99mTc-EDDA/HYNIC-Tyr3-Octreotide has been used in clinical imaging and achieved high impact in management of patients with neuroendocrine tumors. Knowing the limitations and pitfalls is essential to provide ac-curate diagnosis. Therefore, the potential pitfalls associated with the use of 99mTc-EDDA/HYNIC-TOC are reviewed on the basis of own experience. Data were analyzed of 310 patients who underwent somatostatin receptor scintigraphy with 99mTc-Tektrotyd. Pitfalls during radiolabeling process or acquisition can worsen the sensitivity of SRS (somatostatin receptor scintigraphy). Recognizing physi-ological and clinical pitfalls, the diagnostic accuracy will improve.

An improved 99mTc-HYNIC-(Ser)3-LTVSPWY peptide with EDDA/tricine as co-ligands for targeting and imaging of HER2 overexpression tumor.

PubMed

Khodadust, Fatemeh; Ahmadpour, Sajjad; Aligholikhamseh, Nazan; Abedi, Seyed Mohammad; Hosseinimehr, Seyed Jalal

2018-01-20

Overexpression of human epidermal receptor 2 (HER2) has given the opportunity for targeting and delivering of imaging radiotracers. The aim of this study was to evaluate the 99m Tc-HYNIC-(EDDA/tricine)-(Ser) 3 -LTVSPWY peptide for tumor targeting and imaging of tumor with overexpression of HER2. The HYNIC-(Ser) 3 -LTVSPWY was labeled with 99m Tc in presence of EDDA/tricine mixture as co-ligands. The in vitro and in vivo studies of this radiolabeled peptide were performed for cellular specific binding and tumor targeting. The high radiochemical purity of 99m Tc-HYNIC (EDDA/tricine)-(Ser) 3 -LTVSPWY was obtained to be 99%. It exhibited high stability in normal saline and human serum. In HER2 binding affinity study, a significant reduction in uptake of radiolabeled peptide (7.7 fold) was observed by blocking SKOV-3 cells receptors with unlabeled peptide. The K D and B max values for this radiolabeled peptide were determined as 3.3 ± 1.0 nM and 2.9 ± 0.3 × 10 6 CPM/pMol, respectively. Biodistribution study revealed tumor to blood and tumor to muscle ratios about 6.9 and 4 respectively after 4 h. Tumor imaging by gamma camera demonstrated considerable high contrast tumor uptake. This developed 99m Tc-HYNIC-(Ser) 3 -LTVSPWY peptide selectively targeted on HER2 tumor and exhibited a high target uptake combined with acceptable low background activity for tumor imaging in mice. The results of this study and its comparison with another study showed that 99m Tc-HYNIC-(EDDA/tricine)-(Ser) 3 -LTVSPWY is much better than previously reported radiolabeled peptide as 99m Tc-CSSS-LTVSPWY for HER2 overexpression tumor targeting and imaging. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma.

PubMed

Czepczyński, Rafał; Parisella, Maria Gemma; Kosowicz, Jerzy; Mikołajczak, Renata; Ziemnicka, Katarzyna; Gryczyńska, Maria; Sowiński, Jerzy; Signore, Alberto

2007-10-01

Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin analogue (99m)Tc-EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. Forty-five patients with MTC, aged 14-83 years, were investigated. Scintigraphy using (99m)Tc-EDDA/HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and analysed in individual cases (ultrasonography, computed tomography, (99m)Tc(V)-DMSA, (131)I-MIBG, (99m)Tc-MDP, (111)In-DTPA-octreotide and (18)F-FDG-PET) and compared with (99m)Tc-EDDA/HYNIC-TOC. In group 1 (eight patients before thyroidectomy), uptake of the tracer was found in the primary tumours. In group 2 (six patients with remission), a false positive result was found in one patient; in the remaining five patients, no pathological foci were visualised. In group 3 (31 patients with post-surgical hypercalcitoninaemia), scintigraphy was true positive in 23 patients (74.2%): uptake in the thyroid bed was found in five patients, in the lymph nodes in 18 and in bone metastases in four. Using (99m)Tc-EDDA/HYNIC-TOC scintigraphy, the overall sensitivity was 79.5%, specificity 83.3%, accuracy 80.0%, positive predictive value 96.9% and negative predictive value 38.5%. (99m)Tc-EDDA/HYNIC-TOC is clinically useful for scintigraphy in the follow-up of patients with MTC. It can be used in clinical practice for preoperative evaluation, for localisation of local recurrence or distant metastases and particularly for therapy decision making.

Clinical indications to the use of (99m)Tc-EDDA/HYNIC-TOC to detect somatostatin receptor-positive neuroendocrine tumors.

PubMed

Parisella, M G; Chianelli, M; D'Alessandria, C; Todino, V; Mikolajczak, R; Papini, E; Dierckx, R A; Scopinaro, F; Signore, A

2012-02-01

The aim of this study was to define, retrospectively, the utility to perform (99m)Tc-EDDA/HYNIC-Tyr3-octreotide ((99m)Tc-EDDA/HYNIC-TOC) scan in patients with NET. We studied 50 consecutive patients affected by different types of NET and divided in two groups. Group 1: 34 patients with known lesions in which (99m)Tc-EDDA/HYNIC-TOC was performed for staging, characterisation or to choose the appropriate treatment. Group 2: 16 patients suspected of having NET or in follow up after surgery. Patients were injected with 370 MBq of (99m)Tc-EDDA/HYNIC-Tyr3-octreotide and whole-body and SPET images acquired 2-3 hours after injection. Overall, 29 patients (58%) had a positive scan, with a sensitivity, specificity and accuracy of 70.3%, 76.9% and 72%, respectively (78.1%, 50% and 76.5%, in group 1 and 20%, 81.2%, 62.5% in group 2). In patients from group 1 (99m)Tc-HYNIC-TOC scintigraphy showed a concordance of 68% with another imaging procedure and in 9 patients revealed a greater number of lesions. In the second group, false negative results were especially found in patients with medullary thyroid cancer with negative radiological findings and elevated calcitonin. In conclusion, (99m)Tc-EDDA/HYNIC-TOC is highly indicated for in vivo histological characterization of known NET lesions, previously identified by other imaging modalities or biopsy, to plan appropriate therapy especially for patients with inoperable disease. In patients with only biochemical suspicion of NET and in those with negative markers, this scintigraphy does not significantly modify the clinical management.

99mTc-EDDA/HYNIC-octreotate in detection of atypical bronchial carcinoid.

PubMed

Hubalewska-Dydejczyk, A; Fröss-Baron, K; Gołkowski, F; Sowa-Staszczak, A; Mikołajczak, R; Huszno, B

2007-01-01

Pulmonary carcinoids cause serious difficulties in imaging diagnostics in all stages of the disease. SRS holds great promise for detecting occult primary tu and metastatic lesions. (99m)Tc-EDDA/HYNIC-octreotate, a new scintigraphic agent, should significantly improve sensitivity of the diagnostics of carcinoids due to better affinity to SSR2 than (111)In-Octreoscan and the higher count rate obtained from (99m)Tc over (111)In. We present a case of a 40-year-old women operated on because of lung carcinoid tumour in 2002. The symptoms did not resolve after the operation and 5-OHIAA was still elevated. The thorax spiral CT revealed the focal lesion beneath carina. (111)In-Octreoscan and (99m)Tc-EDDA/HYNIC-octreotate SRS revealed two focal lesions in the mediastinum. (99m)Tc-EDDA/HYNIC-octreotate detected two additional lesions in the lower part of the right lung. Target/non-target count ratios of the lesions were as follows: (99m)Tc-EDDA/HYNIC-octreotate scans - 2,9, (111)In-Octreoscan- 2,1. PET-FDG examination revealed no pathology. Owing to severe bone pains and carcinoid symptoms the patient was referred for the 90Y-DOTA-octreotate treatment. SRS with a new 99mTc marked somatostatin analogue - octreotate allows for a more sensitive detection of metastatic leasions in carcinoid tumours. The usefulness of 18F-FDG PET, widely used as a powerful imaging technique in clinical oncology, is limited in detection of carcinoid tumours due to the low proliferative activity.

Comparison of different methods for radiochemical purity testing of [99mTc-EDDA-HYNIC-D-Phe1,Tyr3]-octreotide.

PubMed

von Guggenberg, Elisabeth; Penz, Barbara; Kemmler, Georg; Virgolini, Irene; Decristoforo, Clemens

2006-02-01

[99mTc-EDDA-HYNIC-D-Phe1,Tyr3]-octreotide (99mTc-EDDA-HYNIC-TOC) is an alternative radioligand for somatostatin receptor (SSTR) scintigraphy of neuroendocrine tumours. In order to allow a rapid and accurate determination of the quality in the clinical routine the aim of this study was to evaluate different methods of radiochemical purity (RCP) testing. Three different methods of RCP testing were compared: high-performance liquid chromatography (HPLC), thin layer chromatography (TLC) and minicolumn (Sep-Pak purification = SPE). HPLC was shown to be the most effective method for the quality control. The use of TLC and SPE is only recommended after sufficient practical labelling experience.

99mTc-EDDA/HYNIC-TOC in management of patients with head and neck somatostatin receptor positive tumors.

PubMed

Trogrlic, Mate; Tezak, Stanko

2016-01-01

Aim of this study was to determine the value of technetium-99m-hydrazinonicotinyl-Tyr3-octreotide (99mTc-ED-DA/HYNIC-TOC) in patients with somatostatin receptor (SSR) positive tumors of head and neck region. A total number of 16 patients were enrolled in this study. Planar whole body (WB) and single photon emission computed tomography (SPECT) images were acquired at 2 and 4 hours after the injection of approximately 670 MBq of 99mTc-EDDA/HYNIC-TOC. Additional single photon emission computed tomography/computed tomography (SPECT/CT) images of the head and neck region were acquired at 4h post tracer injection. Clinical and imaging follow up were taken as the reference standard. There were 10 female and 6 male patients of age 57.7 ± 12.9 years (58.5; 32-78) years. 99mTc-EDDA/HYNIC-TOC somatostatin receptor scintigraphy (SRS) was TP in 13 patients, TN in two and FP in one. Follow up period for SRS was 31.1 ± 19.4 (29; 2-63) months. 99mTc-EDDA/HYNIC-TOC scintigraphy provided additional information in 50% of patients, with impact on patient management in the same percentage of patients. Distant metastases were found in nine out of 16 patients (56%). 99mTc-EDDA/HYNIC-TOC SRS had sensitivity of 100% (75.3-100%), specificity of 66.7% (9.4-99.2%), accuracy of 93.7%, positive predictive value of 92.9% (66.1-99.8%), and negative predictive value of 100% (15.8-100%). Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC is very useful imaging method in the evalu-ation of patients with SSR positive tumors of head and neck region.

Imaging experimental intraabdominal abscesses with 99mTc-PEG liposomes and 99mTc-HYNIC IgG.

PubMed Central

Dams, E T; Reijnen, M M; Oyen, W J; Boerman, O C; Laverman, P; Storm, G; van der Meer, J W; Corstens, F H; van Goor, H

1999-01-01

OBJECTIVE: To evaluate the accuracy of technetium-99m-labeled polyethylene glycol-coated liposomes (99mTc-PEG liposomes) and technetium-99m-labeled nonspecific human immunoglobulin G (99mTc-HYNIC IgG) for the scintigraphic detection of experimental intraabdominal abscesses in comparison with that of a standard agent, gallium-67 citrate. BACKGROUND: Scintigraphic imaging techniques can be very useful for the rapid and accurate localization of intraabdominal abscesses. Two newly developed radiolabeled agents, 99mTc-PEG liposomes and 99mTc-HYNIC IgG, have shown to be excellent agents for imaging experimental focal infection, but have not yet been studied in the detection of abdominal abscesses. METHODS: Intraabdominal abscesses were induced in 42 rats using the cecal ligation and puncture technique. Seven days later, randomized groups of rats received 99mTc-PEG liposomes, 99mTc-HYNIC IgG, or 67Ga citrate intravenously. The rats were imaged up to 24 hours after the injection. The biodistribution of the radiolabel was determined by counting dissected tissues ex vivo. Macroscopic intraabdominal abnormalities and focal uptake on the images were independently scored on a semiquantitative scale. RESULTS: 99mTc-PEG liposomes provided the earliest scintigraphic visualization of the abscess (as soon as 2 hours after the injection vs. 4 hours for the other two agents). Liposomes, IgG, and gallium all showed similarly high absolute uptake in the abscess. Focal uptake of liposomes and gallium correlated best with the extent of the macroscopic abnormalities. CONCLUSIONS: 99mTc-PEG liposomes and 99mTc-HYNIC IgG performed at least as well as the standard agent, 67Ga citrate, in the detection of experimental intraabdominal abscesses, with obvious advantages such as lower radiation exposure and more favorable physical properties. Of the two technetium agents, the liposomes seemed to be superior, providing the earliest diagnostic image and the best correlation with the inflammatory

Tricine co-ligand improved the efficacy of 99mTc-HYNIC-(Ser)3-J18 peptide for targeting and imaging of non-small-cell lung cancer.

PubMed

Shaghaghi, Zahra; Abedi, Seyed Mohammad; Hosseinimehr, Seyed Jalal

2018-05-15

The early diagnosis of non-small cell lung cancer (NSCLC) is important for increasing survival rate and improving quality life of patients. The aim of this study was to investigate 99m  Tc-(tricine)-HYNIC-(Ser) 3 -J18 for targeting and imaging of NSCLC in A-549 xenografted nude mice. The (Ser) 3 -J18 peptide was conjugated with HYNIC and labeled with 99m  Tc using tricine as a co-ligand. The radiolabeled peptide was evaluated for its radiochemical purity, stability, receptor binding and internalization in vitro. The future experiments were performed for tumor targeting and imaging in A-549 tumor-bearing mice. 99m  Tc-(tricine)-HYNIC-(Ser) 3 -J18 was obtained at high labeling efficiency at room temperature and favorable stability in saline and human plasma. At the cellular level, the radiolabeled peptide specifically bond to A-549 cells with a K D 4.1 ± 1.3 nM. Biodistribution study revealed tumor to blood and tumor to muscle ratios were about 3.12 and 5.63 respectively after 2 h injection of radiolabeled peptide. These ratios were significantly decreased by co-injection of excess non-labeled peptide in mice. This radiolabeled peptide selectively targeted to NSCLC tumor and exhibited a high target uptake combined with acceptable low background activity for tumor imaging in mice. The results of this study and its comparison with another study showed that 99m  Tc-(tricine)-HYNIC-(Ser) 3 -J18 is better than previously reported radiolabeled peptide as 99m  Tc-(EDDA/tricine)-HYNIC-(Ser) 3 -J18 for NSCLC targeting and imaging. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Fab(nimotuzumab)-HYNIC-99mTc: Antibody Fragmentation for Molecular Imaging Agents.

PubMed

Calzada, Victoria; García, María Fernanda; Alonso-Martínez, Luis Michel; Camachoc, Ximena; Goicochea, Enzo; Fernández, Marcelo; Castillo, Abmel Xiques; Díaz-Miqueli, Arlhee; Iznaga-Escobar, Normando; Montaña, René Leyva; Alonso, Omar; Gambini, Juan Pablo; Cabral, Pablo

2016-01-01

Finally, fast blood clearance nimotuzumab is a humanized monoclonal antibody that recognise, with high specific affinity, the epidermal growth factor receptor (EGF-R) which play an important role in the growth process associated with many solid tumors. In this work, the whole antibody was digested with papain in order to generate a Fab fragment, derivatized with NHS-HYNIC-Tfa and radiolabel with technetium-99m (99mTc) as a potential agent of molecular imaging of cancer. Both, whole and fragment radiolabels were in-vivo and in-vitro characterized. Radiolabeling conditions with Tricine as coligand and quality controls were assessed to confirm the integrity of the labeled fragment. Biodistribution and imaging studies in normal and spontaneous adenocarcinoma mice were performed at different times to determine the in-vivo characteristics of the radiolabel fragment. Tumor localization was visualized by conventional gamma camera imaging studies, and the results were compared with the whole antibody. Also, an immunoreactivity assay was carried out for both. The results showed clearly the integrity of the nimotuzumab fragment and the affinity by the receptor was verified. Fab(nimotuzumab)-HYNIC was obtained with high purity and a simple strategy of radiolabeling was performed. Finally, a fast blood clearance was observed in the biodistribution studies increasing the tumor uptake of Fab(nimotuzumab)- HYNIC-99mTc over time, with tumor/muscle ratios of 3.81 ± 0.50, 5.16 ± 1.97 and 6.32 ± 1.98 at 1 h, 4 h and 24 h post injection. Urinary excretion resulted in 32.89 ± 3.91 %ID eliminated at 24 h. Scintigraphy images showed uptake in the tumor and the activity in non-target organs was consistent with the biodistribution data at the same time points. Hence, these preliminary results showed important further characteristic of Fab(nimotuzumab)-HYNIC-99mTc as a molecular imaging agent of cancer.

Preparation and biological evaluation of [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide for somatostatin receptor-positive tumor imaging.

PubMed

Erfani, Mostafa; Shafiei, Mohammad; Mazidi, Mohammad; Goudarzi, Mostafa

2013-04-01

Somatostatin-derived analogues play an important role in the diagnosis and treatment of neuroendocrine tumors. The aim of this study was to evaluate a new somatostatin analogue designed for labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), β-(3-benzothienyl)-Ala (BzThi(3))]-octreotide ([HYNIC]-BOC), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. Synthesis was performed on a solid phase using a standard Fmoc strategy. The HYNIC-peptide conjugate was radiolabeled with (99m)Tc and characterized by ITLC and high-performance liquid chromatography (HPLC). In vitro studies were carried out in sstr2 expressing AR4-2J cell lines. In vivo distribution studies were performed in rats bearing the AR4-2J tumor. The radiolabeled complex could be prepared at high-specific activities and >95% radiochemical yield as determined by HPLC. The peptide conjugate showed high-affinity binding for sstr2. The radioligand showed high and specific internalization into AR4-2J cells (18.19%±0.21% at 4 hours). In vivo distribution studies in rats bearing tumor have shown a receptor-specific uptake of radioactivity in somatostatin receptor-positive organs. After 4 hours, uptake in the AR4-2J tumor was 1.71%±0.36% injected dose per gram tissue (%ID/g). These data show that [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide is a specific radioligand for the somatostatin receptor-positive tumors and is a suitable candidate for clinical studies.

99mTc-labelled HYNIC-minigastrin with reduced kidney uptake for targeting of CCK-2 receptor-positive tumours.

PubMed

von Guggenberg, E; Dietrich, H; Skvortsova, I; Gabriel, M; Virgolini, I J; Decristoforo, C

2007-08-01

Different attempts have been made to develop a suitable radioligand for targeting CCK-2 receptors in vivo, for staging of medullary thyroid carcinoma (MTC) and other receptor-expressing tumours. After initial successful clinical studies with [DTPA(0),D: Glu(1)]minigastrin (DTPA-MG0) radiolabelled with (111)In and (90)Y, our group developed a (99m)Tc-labelled radioligand, based on HYNIC-MG0. A major drawback observed with these derivatives is their high uptake by the kidneys. In this study we describe the preclinical evaluation of the optimised shortened peptide analogue, [HYNIC(0),D: Glu(1),desGlu(2-6)]minigastrin (HYNIC-MG11). (99m)Tc labelling of HYNIC-MG11 was performed using tricine and EDDA as coligands. Stability experiments were carried out by reversed phase HPLC analysis in PBS, PBS/cysteine and plasma as well as rat liver and kidney homogenates. Receptor binding and cell uptake experiments were performed using AR4-2J rat pancreatic tumour cells. Animal biodistribution was studied in AR4-2J tumour-bearing nude mice. Radiolabelling was performed at high specific activities and radiochemical purity was >90%. (99m)Tc-EDDA-HYNIC-MG11 showed high affinity for the CCK-2 receptor and cell internalisation comparable to that of (99m)Tc-EDDA-HYNIC-MG0. Despite high stability in solution, a low metabolic stability in rat tissue homogenates was found. In a nude mouse tumour model, very low unspecific retention in most organs, rapid renal excretion with reduced renal retention and high tumour uptake were observed. (99m)Tc-EDDA-HYNIC-MG11 shows advantages over (99m)Tc-EDDA-HYNIC-MG0 in terms of lower kidney retention with unchanged uptake in tumours and CCK-2 receptor-positive tissue. However, the lower metabolic stability and impurities formed in the labelling process still leave room for further improvement.

Physiological expression of pancreatic somatostatin receptors in 99mTc-HYNIC-TOC scintigraphy.

PubMed

de la Cueva, L; Lloro, P; Sangrós, M J; López Vélez, L; Navarro, P; Sarria, L; Álvarez, S; Abós, D

2017-07-01

To describe the frequency of head and/or pancreas uncinate process uptake of 99mTc-HYNIC-TOC, to study its nature, and analyze its diagnostic value. Retrospective evaluation of 47 consecutive 99mTc-HYNIC-TOC examinations was conducted. Head and/or pancreas uncinate process uptake was considered to be physiological in patients with normal CT at the same episode and in follow-up. It was analyzed if age or diabetes mellitus was justifying the existence or not of uptake. 32.5% patients showed uptake; 73% of them were mild. 84.6% patients with uptake have no pathology and 4% had neuroendocrine pancreatic disease at CT. Neither the age nor the diabetes mellitus established differences in patients without lesion. Near one-third of patients show physiological uptake by head and/or pancreas uncinate process at 99mTc-HYNIC-TOC scintigraphy. It seems that neither the diabetes nor the ages are factors that determine this physiological uptake.

Introduction of an 8-aminooctanoic acid linker enhances uptake of 99mTc-labeled lactam bridge-cyclized α-MSH peptide in melanoma.

PubMed

Guo, Haixun; Miao, Yubin

2014-12-01

The purpose of this study was to examine the effects of amino acid, hydrocarbon, and polyethylene glycol (PEG) linkers on the melanoma targeting and imaging properties of (99m)Tc-labeled lactam bridge-cyclized HYNIC-linker-Nle-CycMSHhex (hydrazinonicotinamide-linker-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2) peptides. Four novel peptides (HYNIC-GGGNle-CycMSHhex, HYNIC-GSGNle-CycMSHhex, HYNIC-PEG2Nle-CycMSHhex, and HYNIC-AocNle-CycMSHhex) were designed and synthesized. The melanocortin-1 receptor binding affinities of the peptides were determined in B16/F1 melanoma cells. The biodistribution of (99m)Tc(ethylenediaminediacetic acid [EDDA])-HYNIC-GGGNle-CycMSHhex, (99m)Tc(EDDA)-HYNIC-GSGNle-CycMSHhex, (99m)Tc(EDDA)-HYNIC-PEG2Nle-CycMSHhex, and (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex were determined in B16/F1 melanoma-bearing C57 mice at 2 h after injection to select a lead peptide for further evaluation. The melanoma targeting and imaging properties of (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex were further examined because of its high melanoma uptake. The inhibitory concentrations of 50% (IC50) for HYNIC-GGGNle-CycMSHhex, HYNIC-GSGNle-CycMSHhex, HYNIC-PEG2Nle-CycMSHhex, and HYNIC-AocNle-CycMSHhex were 0.7 ± 0.1, 0.8 ± 0.09, 0.4 ± 0.08, and 0.3 ± 0.06 nM, respectively, in B16/F1 melanoma cells. Among these four (99m)Tc-labeled peptides, (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex displayed the highest melanoma uptake (22.3 ± 1.72 percentage injected dose/g) at 2 h after injection. (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex exhibited high tumor-to-normal-organ uptake ratios except for the kidneys. The tumor-to-kidney uptake ratios of (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex were 3.29, 3.63, and 6.78 at 2, 4, and 24 h, respectively, after injection. The melanoma lesions were clearly visualized by SPECT/CT using (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex as an imaging probe at 2 h after injection. High melanoma uptake and fast urinary clearance of (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex highlighted its

Introduction of an 8-Aminooctanoic Acid Linker Enhances the melanoma uptake of Tc-99m-labeled Lactam Bridge-Cyclized Alpha-MSH Peptide

PubMed Central

Guo, Haixun; Miao, Yubin

2015-01-01

The purpose of this study was to examine the effects of amino acid, hydrocarbon and polyethylene glycol (PEG) linkers on melanoma targeting and imaging properties of 99mTc-labeled lactam bridge-cyclized HYNIC-linker-Nle-CycMSHhex {hydrazinonicotinamide-linker-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2} peptides. Methods four novel peptides {HYNIC-GGGNle-CycMSHhex, HYNIC-GSGNle-CycMSHhex, HYNIC-PEG2Nle-CycMSHhex and HYNIC-AocNle-CycMSHhex} were designed and synthesized. The melanocortin-1 (MC1) receptor binding affinities of the peptides were determined in B16/F1 melanoma cells. The biodistribution of 99mTc(EDDA)-HYNIC-GGGNle-CycMSHhex, 99mTc(EDDA)-HYNIC-GSGNle-CycMSHhex, 99mTc(EDDA)-HYNIC-PEG2Nle-CycMSHhex and 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex were determined in B16/F1 melanoma-bearing C57 mice at 2 h post-injection to select a lead peptide for further evaluation. The melanoma targeting and imaging properties of 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex were further examined because of its high melanoma uptake. Results The IC50 values of HYNIC-GGGNle-CycMSHhex, HYNIC-GSGNle-CycMSHhex, HYNIC-PEG2Nle-CycMSHhex, and HYNIC-AocNle-CycMSHhex were 0.7 ± 0.1, 0.8 ± 0.09, 0.4 ± 0.08, and 0.3 ± 0.06 nM in B16/F1 melanoma cells, respectively. Among these four 99mTc-labeled peptides, 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex displayed the highest melanoma uptake (22.3 ± 1.72% ID/g) at 2 h post-injection. 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex exhibited high tumor to normal organ uptake ratios except for the kidneys. The tumor/kidney uptake ratios of 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex were 3.29, 3.63 and 6.78 at 2, 4 and 24 h post-injection. The melanoma lesions were clearly visualized by single photon emission computed tomography (SPECT)/CT using 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex as an imaging probe at 2 h post-injection. Conclusion High melanoma uptake and fast urinary clearance of 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex highlighted its potential for metastatic melanoma detection in the future

Imaging human melanoma using a novel Tc-99m-labeled lactam bridge-cyclized alpha-MSH peptide.

PubMed

Liu, Liqin; Xu, Jingli; Yang, Jianquan; Feng, Changjian; Miao, Yubin

2016-10-01

In this study, the human melanoma targeting property of (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex {hydrazinonicotinamide-8-aminooctanoic acid-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2} was determined in M21 human melanoma-xenografts to demonstrate its potential for human melanoma imaging. The IC50 value of HYNIC-AocNle-CycMSHhex was 0.48±0.01nM in M21 human melanoma cells (1281receptors/cell). The M21 human melanoma uptake of (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex was 4.03±1.25, 3.26±1.23 and 3.36±1.48%ID/g at 0.5, 2 and 4h post-injection, respectively. Approximately 92% of injected dose cleared out the body via urinary system at 2h post-injection. (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex showed high tumor/blood, tumor/muscle and tumor/skin uptake ratios after 2h post-injection. The M21 human melanoma-xenografted tumor lesions were clearly visualized by SPECT/CT using (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex as an imaging probe at 2h post-injection. Overall, (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex exhibited favorable human melanoma imaging property, highlighting its potential as an imaging probe for human metastatic melanoma detection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of tricine and EDDA as Co-ligands for 99mTc-labeled HYNIC-MSH analogs for melanoma imaging.

PubMed

Garcia, Maria Fernanda; Zhang, Xiuli; Gallazzi, Fabio; Fernandez, Marcelo; Moreno, Maria; Gambini, Juan Pablo; Porcal, Williams; Cabral, Pablo; Quinn, Thomas P

2015-01-01

Several radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogs have been studied for their abilities to target melanoma tumor cells through specific recognition and binding to the melanocortin receptor 1 (MCR1). In this work, a lactam bridgecyclized α-MSH analog was labeled with (99m) via the hydrazinonicotinamide (HYNIC) chelator and characterized for its melanoma tumor targeting properties. The bifunctional chelating agent HYNIC-Boc was attached to the N-terminus of the MSH peptide followed by the lactam cyclization, resulting in the HYNIC-cyc-MSH analog. The lactam cyclized peptide displayed high affinity and specificity for MC1-receptors present on B16/F1 melanoma tumor cells, exhibiting an IC50 of 6.48 nM. HYNIC-cyc-MSH was radiolabeled with (99m)Tc using two common co-ligands, tricine and EDDA. In vitro, the radiochemical stability, cell binding and efflux properties were similar between the peptides radiolabeled with tricine and EDDA as co-ligands. In vivo, biodistribution studies (n=4) demonstrated that (99m)Tc- HYNIC-cyc-MSH/tricine had superior tumor to muscle and tumor to blood ratios than (99m)Tc-HYNIC-cyc-MSH/EDDA at early time points. Planar gamma imaging of melanoma bearing mice showed that 99mTc-HYNIC-cyc-MSH/tricine was able to clearly visualize tumors, underscoring the potential utility of (99m)Tc labeled lactam cyclized MSH molecules as melanoma imaging agents.

Improved kit formulation for preparation of (99m)Tc-HYNIC-TOC: results of preliminary clinical evaluation in imaging patients with neuroendocrine tumors.

PubMed

Korde, Aruna; Mallia, Madhava; Shinto, Ajit; Sarma, H D; Samuel, Grace; Banerjee, Sharmila

2014-11-01

(99m)Tc-HYNIC-TOC is a cost-effective and logistically viable agent for scintigraphy of neuroendocrine tumors overexpressing somatostatin receptors as compared with [(111)In-DTPA-D-Phe(1)] Octreotide (Octreoscan(®)). Several studies have been reported, wherein the efficacy of this agent is demonstrated. In the present article, the authors report the preparation of a single-vial HYNIC-TOC kit suitable for the preparation of 4-5 patient doses (15 mCi/patient) of (99m)Tc-HYNIC-TOC. The kits were tested for sterility and bacterial endotoxins to assure safety of the product. A significant modification in this kit is the inclusion of buffer in the kit itself, unlike in commercially available kits where the buffer solution has to be added during preparation. (99m)Tc-HYNIC-TOC was prepared by adding 20-80 mCi (740-2960 MBq) of freshly eluted Na(99m)TcO4 in 1-3 mL of sterile saline directly into the kit vial and heating the vial in a water bath at 100°C for 20 minutes. The labeling yield and radiochemical purity of (99m)Tc-HYNIC-TOC, prepared using the lyophilized cold kit, were consistently >90%. The kits were evaluated over a period of 9 months and found to be stable when stored at -20°C. Limited clinical studies performed with the (99m)Tc-HYNIC-TOC, formulated using the kit, showed adequate sensitivity and specificity for the detection of gasteroenteropancreatic neuroendocrine tumors.

Comparative analysis of 99mTc-depreotide and 99mTc-EDDA/HYNIC-TOC thorax scintigrams acquired for the purpose of differential diagnosis of solitary pulmonary nodules.

PubMed

Płachcińska, Anna; Mikołajczak, Renata; Kozak, Józef; Rzeszutek, Katarzyna; Kuśmierek, Jacek

2006-01-01

Aiming at comparison of diagnostic efficacy of 2 radiopharmaceuticals: 99mTc-depreotide (Neospect, Amersham) and 99mTc-EDDA/HYNIC-Tyr3-octreotide (Tektrotyd, Polatom), in differentiation between malignant and benign etiology of solitary pulmonary nodules (SPNs), radionuclide studies with 2 radiotracers were performed in 18 patients. For both radiopharmaceuticals the same acquisition and processing protocols were applied. Studies were acquired with SPECT technique, after administration of 740 MBq of activity. Scintigrams were assessed visually, as: positive (+), equivocal (+/-) and negative (-). Additionally, uptake intensity of both radiotracers in nodules was assessed semiquantitatively, using a tumour-to-background ratio. Verification of scintigraphic results was based in 14 cases upon a pathological examination of tumour samples (histopathology) and in the remaining 4 - on clinical observation and bacteriological studies. Normal scintigrams obtained with both radiopharmaceuticals differed significantly. 99mTc-depreotide was markedly accumulated in spine, sternum, ribs and lungs (mean lung/heart ratio = 2.2). This accumulation was not observed on 99mTc- -EDDA/HYNIC-TOC scintigrams (mean lung/heart ratio = 0.7). In 6 patients a malignant etiology--lung cancer--was revealed (5--adenocarcinoma, 1--squamous cell) and the other 12 cases turned out to be benign (4 hamartomas, 3 tuberculomas, a tuberculous infiltrate, an alien body with inflammatory reaction, a hyperplasia of lymphatic tissue and 2 cases of unknown etiology, from which one had a stable size and the other resolved during a 6 month observation period). In all 6 cases of lung cancer positive results were obtained with both tracers. Moreover, in 2 patients metastases in mediastinum could be observed on scintigrams obtained with both radiopharmaceuticals. From among 12 cases of benign etiology 6 99mTc-depreotide scintigrams were true negative, 1--equivocal and 5--false positive, whereas 6 99mTc-EDDA/HYNIC

99mTc-HYNIC-TOC increased uptake can mimic malignancy in the pancreas uncinate process at somatostatin receptor SPECT/CT.

PubMed

Yamaga, Lilian Yuri Itaya; Neto, Guilherme Campos Carvalho; da Cunha, Marcelo Livorsi; Osawa, Akemi; Oliveira, Julio Cesar Silveira; Fonseca, Ricardo Quartim; Nogueira, Solange Amorim; Wagner, Jairo; Funari, Marcelo Gusmão

2016-03-01

The aim of this study was to assess the occurrence and frequency of increased physiologic uptake of 99mTc-HYNIC-TOC by the uncinate process of the pancreas in SPECT/CT images. Forty-six scans of 41 patients were evaluated retrospectively. The uptake of 99mTc-HYNIC-TOC was considered to be physiologic in patients with normal findings at dedicated abdominal CT or MR and lack of neoplastic lesions in clinical follow-ups. The intensity of uncinate process uptake was compared to the uptake of the normal liver. Focal uptake was attributed to the presence of pancreatic NET in 5 patients. Among the 36 patients without any evidence of malignancy in CT, MR and follow-up, 7 (19.4 %) showed increased uptake in the uncinate process. The intensity of uptake was lesser in 3 (8.3 %), similar in 3 and greater than the normal liver in 1 (2.8 %) case. Increased 99mTc-HYNIC-TOC uptake occurred in 19.4 % of those subjects without any evidence of neuroendocrine tumor in the uncinate process.

[99mTc] HYNIC-hEGF, a potential agent for imaging of EGF receptors in vivo: preparation and pre-clinical evaluation.

PubMed

Babaei, Mohammad Hossein; Almqvist, Ylva; Orlova, Anna; Shafii, Mohammad; Kairemo, Kalevi; Tolmachev, Vladimir

2005-06-01

Expression of epidermal growth factor receptors (EGFR) has prognostic and predictive value in many kinds of tumors. Imaging of expression of EGFR in vivo may give valuable diagnostic information. The epidermal growth factor (EGF), a natural ligand, is a possible candidate for the targeting of EGFR. The present study describes a method for preparation of (99m)Tc-EGF via the hydrazinopyridine-3-carboxylic acid (HYNIC) conjugation using tricine and ethylenediamine-N,N'-diacetic acid (EDDA) as co-ligands. Both conjugates bound EGFR expressing cells with nanomolar affinity, and demonstrated good intracellular retention. The complex with EDDA demonstrated much higher stability in blood serum and during cysteine challenge. Biodistribution of (99m)Tc-EDDA-HYNIC-EGF in normal mice demonstrated fast blood clearance of conjugate, and its ability to bind EGFR in vivo. (99m)Tc-EDDA-HYNIC-EGF is a promising candidate for visualization of EGFR expression in vivo.

Evaluation of [99mTc/EDDA/HYNIC0]octreotide derivatives compared with [111In-DOTA0,Tyr3, Thr8]octreotide and [111In-DTPA0]octreotide: does tumor or pancreas uptake correlate with the rate of internalization?

PubMed

Storch, Daniel; Béhé, Martin; Walter, Martin A; Chen, Jianhua; Powell, Pia; Mikolajczak, Renata; Mäcke, Helmut R

2005-09-01

Radiolabeled somatostatin analogs are important tools for the in vivo localization and targeted radionuclide therapy of somatostatin receptor-positive tumors. The aim of this study was to compare 3 somatostatin analogs designed for the labeling with (99m)Tc (where HYNIC is 6-hydrazinopyridine-3-carboxylic acid): 6-hydrazinopyridine-3-carboxylic acid(0)-octreotide (HYNIC-OC/(99m)Tc-(1)), [HYNIC(0),Tyr(3)]octreotide (HYNIC-TOC/(99m)Tc-(2)), and [HYNIC(0),Tyr(3),Thr(8)]octreotide (HYNIC-TATE/(99m)Tc-(3)), using ethylenediamine-N,N'-diacetic acid (EDDA) as a coligand. In addition, we compared the (99m)Tc-labeled peptides [(111)In-diethylenetriaminepentaacetic acid(0)]octreotide ([(111)In-DTPA]-OC) and [(111)In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(0),Tyr(3),Thr(8)]octreotide ([(111)In-DOTA]-TATE) with regard to the rate of internalization and the biodistribution in AR4-2J (expressing the somatostatin receptor subtype 2) tumor-bearing rats. The main attention was directed toward a potential correlation between the rate of internalization and the tumor or pancreas uptake. Synthesis was performed on solid phase using a standard Fmoc strategy. Internalization was studied in cell culture (AR4-2J) and biodistribution was studied using a Lewis rat tumor model (AR4-2J). The 5 radiopeptides showed a specific internalization into AR4-2J cells in culture (as shown by blocking experiments). The rate of internalization of the 5 radiopeptides differed significantly according to the following order: (99m)Tc-(1) approximately = [(111)In-DTPA]-OC < (99m)Tc-(2) < (99m)Tc-(3) approximately = [(111)In-DOTA]-TATE. All radiopeptides displayed a rapid blood clearance and a fast clearance from all somatostatin receptor-negative tissues predominantly via the kidneys. A receptor-specific uptake of radioactivity was observed for all compounds in somatostatin receptor-positive organs such as the pancreas, the adrenals, and the stomach. After 4 h, the uptake in the AR4-2J tumor

Diagnostic utility of 99mTc-EDDA-tricine-HYNIC-Tyr3-octreotate SPECT for differentiation of active from inactive pulmonary tuberculosis.

PubMed

Ahmadihosseini, Hossein; Abedi, Javad; Ghodsi Rad, Mohammad A; Zakavi, Seyed R; Knoll, Peter; Mirzaei, Siroos; Sadeghi, Ramin

2014-12-01

The current study was performed to evaluate the impact of Tc-EDDA-tricine-HYNIC-Tyr-octreotate in the differentiation of active from inactive pulmonary tuberculosis lesions. Ten consecutive patients (six male and four female, age range 24-83 years) with proven pulmonary tuberculosis (with a positive smear or culture) were enrolled in the study. At 120 min after injection of 740 MBq of Tc-EDDA-tricine-HYNIC-Tyr-octreotate, planar and single-photon emission computed tomography (SPECT) images of the thorax were taken. A semiquantitative evaluation of lesion and nonlesion areas was performed. The scan was repeated following the same protocol after standard treatment for tuberculosis after a negative sputum culture. Semiquantitative evaluation of the lesions showed a statistically significant higher uptake before treatment in both planar and SPECT images (P=0.005 and 0.007, respectively). Lesion-to-nonlesion ratios were also higher in the pretreatment sets on both planar and SPECT images (1.4±0.2 vs. 1.19±0.15, P=0.001, for planar images and 2.32±0.55 vs. 1.32±0.32, P=0.0001, for SPECT images). Tc-EDDA-tricine-HYNIC-Tyr-octreotate scintigraphy may help to differentiate between active and inactive pulmonary tuberculosis. SPECT imaging and semiquantitative evaluation are indispensable for increasing the diagnostic yield of this method. Larger studies are needed to corroborate our results.

The utility of 99mTc-EDDA/HYNIC-TOC scintigraphy for assessment of lung lesions in patients with neuroendocrine tumors.

PubMed

Pavlovic, S; Artiko, V; Sobic-Saranovic, D; Damjanovic, S; Popovic, B; Jakovic, R; Petrasinovic, Z; Jaksic, E; Todorovic-Tirnanic, M; Saranovic, D; Micev, M; Novosel, S; Nikolic, N; Obradovic, V

2010-01-01

Our aim was to assess clinical utility of 99mTc-EDDA/HYNIC-TOC scintigraphy for evaluation of lung lesions in patients with neuroendocrine tumors (NETs). Single photon emission computed tomography (SPECT) of the thorax and whole body scintigraphy were performed in 34 patients using 99mTc-EDDA/HYNIC-TOC. Visual assessment was complemented by semiquantitative evaluation based on tumor to non-tumor (T/NT) ratio. Clinical, laboratory, and histological findings served as the standard for comparison. Enhanced tracer uptake was observed on both SPECT and whole body scintigraphy in 29 of 34 patients (88% sensitivity). T/NT ratios were significantly higher on SPECT than whole body images (2.96+/-1.07 vs.1.70+/-0.43, p 99mTc-EDDA/Hynic-TOC, lung involvement of NETs, T/NT ratio.

Diagnostic sensitivity of Tc-99m HYNIC PSMA SPECT/CT in prostate carcinoma: A comparative analysis with Ga-68 PSMA PET/CT.

PubMed

Lawal, Ismaheel O; Ankrah, Alfred O; Mokgoro, Neo P; Vorster, Mariza; Maes, Alex; Sathekge, Mike M

2017-08-01

Emerging data from published studies are demonstrating the superiority of Ga-68 PSMA PET/CT imaging in prostate cancer. However, the low yield of the Ge-68/Ga-68 from which Gallium-68 is obtained and fewer installed PET/CT systems compared to the SPECT imaging systems may limit its availability. We, therefore, evaluated in a head-to-head comparison, the diagnostic sensitivity of Ga-68 PSMA PET/CT and Tc-99m PSMA SPECT/CT in patients with prostate cancer. A total of 14 patients with histologically confirmed prostate cancer were prospectively recruited to undergo Ga-68 PSMA PET/CT and Tc-99m HYNIC PSMA SPECT/CT. The mean age of patients was 67.21 ± 8.15 years and the median PSA level was 45.18 ng/mL (range = 1.51-687 ng/mL). SUVmax of all lesions and the size of lymph nodes with PSMA avidity on Ga-68 PSMA PET/CT were determined. Proportions of these lesions detected on Tc-99m HYNIC PSMA SPECT/CT read independent of PET/CT findings were determined. A total of 46 lesions were seen on Ga-68 PSMA PET/CT localized to the prostate (n = 10), lymph nodes (n = 24), and bones (n = 12). Of these, Tc-99m HYNIC PSMA SPECT/CT detected 36 lesions: Prostate = 10/10 (100%), lymph nodes = 15/24 (62.5%), and bones = 11/12 (91.7%) with an overall sensitivity of 78.3%. Lesions detected on Tc-99m HYNIC PSMA SPECT/CT were bigger in size (P < 0.001) and had higher SUVmax (P < 0.001) as measured on Ga-68 PSMA PET/CT compared to those lesions that were not detected. All lymph nodes greater than 10 mm in size were detected while only 28% of nodes less than 10 mm were detected by Tc-99m HYNIC PSMA SPECT/CT. In a univariate analysis, Lymph node size (P = 0.033) and the SUVmax of all lesions (P = 0.007) were significant predictors of lesion detection on Tc-99m HYNIC PSMA SPECT/CT. Tc-99m HYNIC PSMA may be a useful in imaging of prostate cancer although with a lower sensitivity for lesion detection compared to Ga-68 PSMA PET/CT. Its use is

Clinical application of 99mTc-HYNIC-TOC SPECT/CT in diagnosing and monitoring of pancreatic neuroendocrine neoplasms.

PubMed

Xu, Junyan; Li, Yi; Xu, Xiaoping; Zhang, Jiangang; Zhang, Yingjian; Yu, Xianjun; Huang, Dan

2018-06-20

Our aim of this research was to determine the value of SPECT/CT with 99m Tc-HYNIC-TOC for evaluation of the pancreatic masses which were suspected as neuroendocrine neoplasms and follow-up of patients with pancreatic neuroendocrine neoplasms. We retrospectively analyzed 184 patients who performed 99m Tc-HYNIC-TOC SPECT/CT. All the patients were divided into two groups: one for assessment of diagnostic efficiency for pancreatic suspected masses (n = 140) and another for monitoring recurrence after surgery (n = 44). The image findings acquired at 2 h postinjection were compared to final diagnoses from pathological results and clinical follow-up. Then, the correlation between ratios of tumor-to-background (TBR) and tumor grade was analyzed. In group 1, 95/140 (67.9%) patients were confirmed as neuroendocrine neoplasms including 85 neuroendocrine tumors and 10 neuroendocrine carcinomas. Patient-based analysis showed that the sensitivity, specificity and accuracy of diagnosing neuroendocrine neoplasms with SPECT/CT were 81.1, 84.4 and 82.1%. There was significant difference of TBRs among G1, G2 and G3 (F = 3.175, P = 0.048). In group 2, 22/44 (50.0%) patients occurred metastasis mainly in liver. The sensitivity, specificity and accuracy of monitoring recurrence were 87.0, 100 and 93.2%. 99m Tc-HYNIC-TOC SPECT/CT is a reliable method of diagnosing and monitoring of pancreatic neuroendocrine neoplasms, especially neuroendocrine tumors.

Osteomalacia-inducing renal clear cell carcinoma uncovered by 99mTc-Hydrazinonicotinyl-Tyr3-octreotide (99mTc-HYNIC-TOC) scintigraphy.

PubMed

Jin, Xiaona; Jing, Hongli; Li, Fang; Zhuang, Hongming

2013-11-01

Most osteomalacia-causing tumors are small, benign mesenchymal neoplasms, which are commonly located in the extremities or craniofacial regions. An 18-year-old male patient with suspicion of tumor-induced osteomalacia underwent (99m)Tc-HYNIC-TOC scintigraphy to search potential culprit tumor. The images showed a large activity in the region of the left kidney. The lesion was resected and a clear cell renal cell carcinoma was found. One year after the left nephrectomy, the patient was tumor-free without symptoms of osteomalacia.

Radiopharmaceutical development of a freeze-dried kit formulation for the preparation of [99mTc-EDDA-HYNIC-D-Phe1, Tyr3]-octreotide, a somatostatin analog for tumor diagnosis.

PubMed

Guggenberg, Elisabeth Von; Mikolajczak, Renata; Janota, Barbara; Riccabona, Georg; Decristoforo, Clemens

2004-10-01

[(99m)Tc-EDDA-HYNIC-D-Phe(1),Tyr(3)]-Octreotide ((99m)Tc-EDDA/HYNIC-TOC) is a promising new radiopharmaceutical with the potential to replace [(111)In-DTPA-D-Phe(1)]-Octreotide ((111)In-DTPA-OCT) as the radiopharmaceutical for somatostatin receptor scintigraphy due to the advantage of improved image quality, lower radiation dose for the patient, and daily availability. Here we describe the development of a freeze-dried kit formulation based on the Tricine/EDDA exchange labeling approach for the preparation of this radiopharmaceutical in a clinical setting. Three parameters were of major importance to achieve a suitable formulation with a radiochemical purity (RCP) >90%: addition of bulking agent, the pH of the freeze-drying solution, and the content of stannous chloride. The final formulation consisted of 20 mg Tricine, 10 mg EDDA, 50 mg Mannitol, 20 microg SnCl(2). 2H(2)O, and 20 microg [HYNIC-D-Phe(1), Tyr(3)]-Octreotide (HYNIC-TOC). Radiolabeling was performed by addition of 0.2 M Na(2)HPO(4) to adjust the pH to 6-7, followed by 0.5-2 GBq (99m)Tc sodium pertechnetate, in a total volume of 2 mL and incubation for 10 min in a boiling water bath. Mean RCP values of 10 batches showed values >90% over a storage period of up to 1 year, a high stability up to 24 h of the final preparation, and retained biological activity. The developed kit formulation forms the basis for further clinical evaluation of this promising new radiopharmaceutical. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association

Biological Evaluation of 99mTc-HYNIC-EDDA/tricine-(Ser)-D4 Peptide for Tumor Targeting.

PubMed

Kazemi, Ziba; Zahmatkesh, Mona Haddad; Abedi, Seyed Mohammad; Hosseinimehr, Seyed Jalal

2017-08-24

D4 small peptide (Leu-Ala-Arg-Leu-Leu-Thr) was selected as an appropriate agent for specific targeting of epidermal growth factor receptor (EGFR). The aim of study was to investigate the 99mTc-labeled D4 peptide for non-small cell lung tumor targeting. HYNIC-(Ser)3-D4 peptide was labeled with 99mTc using mixture of tricine and ethylenediamine diacetic acid (EDDA) as co-ligands. The in vitro cellular uptake of radiolabeled peptide was evaluated by blocking test on human non-small cell lung cancer (A-549) cell line and its biodistribution was evaluated in A-549 xenografted nude mice. This conjugated peptide was labeled with 99mTc in high radiochemical purity and it was highly stable in buffer and serum. The un-blocked to blocked cellular radioactivity ratio was 4- fold that showed a specific binding of this radiolabeled peptide on A-549 cell. Animal biodistribution in A-549 xenografted nude mice showed rapid clearance from blood and other non-target organs. Tumor uptake values as %ID/g (percentage of injection dose per gram of tissue) were 2.47% and 1.30% at 1 and 4 h after injection. This study showed the 99mTc-EDDA/tricine-HYNIC-(Ser)3-D4 peptide had tumor targeting on the non-small cell lung tumor. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Kit preparation and biokinetics in women of 99mTc-EDDA/HYNIC-E-[c(RGDfK)]2 for breast cancer imaging.

PubMed

Ortiz-Arzate, Zareth; Santos-Cuevas, Clara L; Ocampo-García, Blanca E; Ferro-Flores, Guillermina; García-Becerra, Rocío; Estrada, Gisela; Gómez-Argumosa, Edgar; Izquierdo-Sánchez, Vanessa

2014-04-01

In breast cancer, α(ν)β(3) and/or α(ν)β(5) integrins are overexpressed in both endothelial and tumour cells. Radiolabelled peptides based on the Arg-Gly-Asp (RGD) sequence are radiopharmaceuticals with high affinity and selectivity for these integrins. The RGD-dimer peptide (E-[c(RGDfK)]2) radiolabelled with (99m)Tc has been reported as a radiopharmaceutical with a 10-fold higher affinity for the α(ν)β(3) integrin compared with the RGD-monomer. Ethylenediamine-N,N'-diacetic acid (EDDA) is a hydrophilic molecule that may favour renal excretion when used as coligand in the (99m)Tc labelling of hydrazinonicotinamide (HYNIC) peptides and can easily be formulated in a lyophilized kit. The aim of this study was to establish a biokinetic model for (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2 prepared from lyophilized kits and evaluate its dosimetry as a tumour-imaging agent in seven healthy women and three breast cancer patients. (99m)Tc labelling was performed by adding sodium pertechnetate solution and 0.2 mol/l phosphate buffer (pH 7.0) to a lyophilized formulation containing E-[c(RGDfK)]2, EDDA, tricine, mannitol and stannous chloride. The radiochemical purity was evaluated using reverse-phase high-performance liquid chromatography and instant thin-layer chromatography on silica gel analyses. Stability studies in human serum were carried out using size-exclusion high-performance liquid chromatography. In-vitro cell uptake was tested using breast cancer cells (MCF7, T47D and MDA-MB-231) with blocked and nonblocked receptors. Biodistribution and tumour uptake were determined in MCF7 tumour-bearing nude mice with blocked and nonblocked receptors, and images were obtained using a micro-SPECT/PET/CT. Whole-body images from seven healthy women were acquired at 0.5, 1, 3, 6 and 24 h after (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2 administration with radiochemical purities greater than 94%. Regions of interest were drawn around the source organs at each time frame. Each region of

Metastatic melanoma imaging using a novel Tc-99m-labeled lactam-cyclized alpha-MSH peptide.

PubMed

Liu, Liqin; Xu, Jingli; Yang, Jianquan; Feng, Changjian; Miao, Yubin

2017-11-15

The purpose of this study was to determine the metastatic melanoma imaging property of 99m Tc(EDDA)-HYNIC-Aoc-Nle-CycMSH hex {hydrazinonicotinamide-8-aminooctanoic acid-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH 2 }. HYNIC-Aoc-Nle-CycMSH hex was synthesized using fluorenylmethyloxy carbonyl (Fmoc) chemistry. The IC 50 value of HYNIC-Aoc-Nle-CycMSH hex was 0.78 ± 0.13 nM for B16/F10 melanoma cells. 99m Tc(EDDA)-HYNIC-Aoc-Nle-CycMSH hex displayed significantly higher uptake (14.26 ± 2.74 and 10.45 ± 2.31% ID/g) in B16/F10 metastatic melanoma-bearing lung than that in normal lung (0.90 ± 0.15 and 0.53 ± 0.14% ID/g) at 2 and 4 h post-injection, respectively. B16/F10 pulmonary metastatic melanoma lesions were clearly visualized by SPECT/CT using 99m Tc(EDDA)-HYNIC-Aoc-Nle-CycMSH hex as an imaging probe at 2 h post-injection, underscoring its potential as an imaging probe for metastatic melanoma detection. Copyright © 2017 Elsevier Ltd. All rights reserved.

99mTc-EDDA/HYNIC-TOC: a new 99mTc-labelled radiopharmaceutical for imaging somatostatin receptor-positive tumours; first clinical results and intra-patient comparison with 111In-labelled octreotide derivatives.

PubMed

Decristoforo, C; Mather, S J; Cholewinski, W; Donnemiller, E; Riccabona, G; Moncayo, R

2000-09-01

[111In-diethylene triamine penta-acetic acid-D-Phe1]-octreotide (DTPA-octreotide) scintigraphy has gained widespread acceptance as a diagnostic clinical procedure in oncology for imaging somatostatin receptor-positive tumours. However, indium-111 as a radiolabel has several drawbacks, including limited availability, suboptimal gamma energy and high radiation burden to the patient. We have recently reported on the preclinical development of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative which showed promising results both in vitro and in vivo. We now report our initial clinical experiences with this new radiopharmaceutical in ten oncological patients. The clinical diagnoses were: carcinoid syndrome (n=5), thyroid cancer (n=3), pancreatic cancer (n=1) and pituitary tumour (n=1). The biodistribution and kinetics of 99mTc-EDDA/HYNIC-TOC were compared with those of 111In-DTPA-octreotide in six cases, and with those of 111In-DOTA-TOC in five cases. With the new tracer tumours were imaged within 15 min after injection and showed the highest target/non-target ratios 4 h after injection. Tumour uptake persisted up to 20 h p.i. The rate of blood clearance was similar to that of 111In-DTPA-octreotide but faster than that of 111In-DOTA-TOC, while urinary excretion was lower compared with the 111In derivatives. Semi-quantitative region of interest analysis showed that 99mTc-EDDA/HYNIC-TOC produced higher tumour/organ (target/non-target) ratios than the 111In derivatives, especially in relation to heart and muscle. Significantly more lesions could be detected in 99mTc images. We conclude that 99mTcEDDA/HYNIC-TOC shows better imaging properties for the identification of somatostatin receptor-positive tumour sites than currently available 111In-labelled octreotide derivatives.

Clinical translation of a PSMA inhibitor for 99mTc-based SPECT.

PubMed

Ferro-Flores, Guillermina; Luna-Gutiérrez, Myrna; Ocampo-García, Blanca; Santos-Cuevas, Clara; Azorín-Vega, Erika; Jiménez-Mancilla, Nallely; Orocio-Rodríguez, Emmanuel; Davanzo, Jenny; García-Pérez, Francisco O

2017-05-01

Prostate-specific membrane antigen (PSMA) is highly over-expressed in advanced prostate cancers. 68 Ga-labeled PSMA inhibitors (iPSMA) are currently used for prostate cancer detection by PET imaging. The availability of simple, efficient and reproducible radiolabeling procedures is essential for developing new SPECT radiopharmaceuticals for clinical translation. The aim of this research was to prepare 99m Tc-EDDA/HYNIC-Lys(Nal)-Urea-Glu ( 99m Tc-EDDA/HYNIC-iPSMA) obtained from lyophilized kit formulations and evaluate the in vitro and in vivo radiopharmaceutical binding to prostate cancer cells over-expressing PSMA, as well as the 99m Tc-EDDA/HYNIC-iPSMA normal biodistribution in humans and the preliminary uptake in patients with prostate cancer. 99m Tc labeling was performed by adding sodium pertechnetate solution and a 0.2M phosphate buffer (pH 7.0) to a lyophilized formulation containing HYNIC-iPSMA, EDDA, tricine, mannitol and stannous chloride. The radiochemical purity was evaluated by reversed-phase HPLC and ITLC-SG analyses. Stability studies in human serum were performed by size-exclusion HPLC. In vitro cell uptake was tested using prostate cancer cells (LNCaP) with blocked and non-blocked receptors. Biodistribution and tumor uptake were determined in LNCaP tumor-bearing nude mice with blocked and non-blocked receptors, and images were obtained using a micro-SPECT/CT. Whole-body images from three healthy men and two patients with histologically-confirmed prostate cancer (one of them with a previous 68 Ga-PSMA-617scan) were acquired at 1h and 3h after 99m Tc-EDDA/HYNIC-iPSMA administration with radiochemical purities of >98%. In vitro and in vivo studies showed high radiopharmaceutical stability in human serum, specific recognition for PSMA, high tumor uptake (10.22±2.96% ID/g at 1h) with rapid blood clearance and mainly kidney elimination. Preliminary images in patients demonstrated the ability of 99m Tc-EDDA/HYNIC-iPSMA to detect tumors and metastases of

Metastatic Neuroendocrine Carcinoma of the Breast Identified by Tc-99m-HYNIC-TOC SPECT/CT: A Rare Case Report.

PubMed

Claimon, Apichaya; Chuthapisith, Suebwong; Samarnthai, Norasate; Pusuwan, Pawana

2015-08-01

The authors reported an uncommon presentation of metastatic neuroendocrine carcinoma to the breast detected by Tc-99m-HYNIC-TOC SPECT/CT in a 49 years old woman who, previously, had carcinoid tumor of left main bronchus and invasive ductal carcinoma of the right breast. Later, the patient developed left breast mass. Core needle biopsy of the mass revealed poorly differentiated invasive ductal carcinoma. The disease remained stable for 12 years without any treatment on that left breast (due to patient's rejection). On the later investigation using Tc-99m-HYNIC-TOC scintigraphy examination, rather than invasive ductal carcinoma, metastatic neuroendocrine cancer was suggested. The final diagnosis was confirmed by pathological examination after surgical excision. Multiple metastatic lesions of neuroendocrine carcinoma at lung, liver, ovaries, and bones were also depicted. Due to the good behavior of the disease, patient had been doing well for eight months, without specific treatment. This report confirmed the advantage and the accuracy of Tc-99m-HYNIC-TOC scintigraphy in detection of neuroendocrine carcinoma. Furthermore, metastatic neuroendocrine tumor should be in differential diagnosis for patient with breast mass together with history of neuroendocrine tumor

(99m)Tc-EDDA/HYNIC-octreotate - a new radiotracer for detection and staging of NET: a case of metastatic duodenal carcinoid.

PubMed

Hubalewska-Dydejczyk, Alicja; Szybiński, Piotr; Fröss-Baron, Katarzyna; Mikolajczak, Renata; Huszno, Bohdan; Sowa-Staszczak, Anna

2005-01-01

Somatostatin receptor scintigraphy (SRS) has become a routine imaging method for the diagnostics of neuroendocrine tumours (NET). (99m)Tc-EDDA/HYNIC-octreotate (Polatom, Poland) is a new radiotracer with high affinity for SSTR2 and similar physiological biodistribution to (111)In-Octreoscan. We present a case of a 47-year-old man with disseminated duodenal carcinoid. The patient had been operated due to the tumour mass detected in pancreatic head area. Histopathology revealed carcinoid of the duodenal wall with local lymph node and liver metastases. The patient was qualified for chemotherapy stopped due to severe leucopenia. (99m)Tc EDDA/HYNIC-octreotate scintigraphy was performed for staging and to determine SSTR status of the tumour before planned 90Y-DOTATATE therapy. The multiple metastatic lesions were detected all over the body. The high quality images with high target/non target ratio were obtained. (99m)Tc-MDP scintigraphy confirmed multiple bone metastases. On the basis of SRS result the patient was qualified for 90Y-DOTA-TATE therapy. In conclusion, (99m)Tc EDDA/HYNIC-octreotate can be regarded as a promising tracer for staging and to determine SSTR status of NET.

The Diagnostic Efficiency of 99mTc-EDDA/HYNIC-Octreotate SPECT-CT in Comparison with 111In-Pentetrotide in the Detection of Neuroendocrine Tumours

PubMed Central

Koçyiğit Deveci, Emel; Ocak, Meltem; Bozkurt, Murat Fani; Türker, Selcan; Kabasakal, Levent; Uğur, Ömer

2013-01-01

Objective: The aim of this study was to assess the diagnostic efficiency of 99mTc-EDDA/HYNIC-Octreotate in comparison with 111Inpentetrotide scintigraphy in the detection of neuroendocrine tumors. This study also evaluates the impact of SPECT-CT hybrid imaging on somatostatin receptor scintigraphy (SRS) interpretation and clinical management of these tumors. Methods: Fourteen patients were included in the study. All patients underwent a whole body and SPECT-CT imaging with both 99mTc- EDDA/HYNIC-octreotate and 111In-pentetrotide. Images were evaluated both visually and semiquantitatively. Results: On patient basis, the diagnostic results of both studies were similar. The number of lesions detected by 99mTc- EDDA/HYNICOctreotate were higher than the number of lesions detected by 111In-pentetrotide however the difference was not significant (40/43( 93%), 36/43 (83%) p=0.109). Semiquantitative analysis showed higher tumor/organ count ratios for both whole-body and SPECT 99mTc- EDDA/HYNIC-Octreotate scans. Conclusion: The results of this study suggested that, 99mTc- EDDA/HYNIC-Octreotate may be a better alternative to 111In- pentetrotide due to high image quality and lower radiation dose. SPECT/CT is a valuable tool for the assessment of neuroendocrine tumors by providing the precise anatomic localization of scintigraphic findings thus improving lesion detectability and characterization. Conflict of interest:None declared. PMID:24416622

The Diagnostic Efficiency of 99mTc-EDDA/HYNIC-Octreotate SPECT-CT in Comparison with 111In-Pentetrotide in the Detection of Neuroendocrine Tumours.

PubMed

Koçyiğit Deveci, Emel; Ocak, Meltem; Bozkurt, Murat Fani; Türker, Selcan; Kabasakal, Levent; Uğur, Omer

2013-12-01

The aim of this study was to assess the diagnostic efficiency of (99m)Tc-EDDA/HYNIC-Octreotate in comparison with (111)Inpentetrotide scintigraphy in the detection of neuroendocrine tumors. This study also evaluates the impact of SPECT-CT hybrid imaging on somatostatin receptor scintigraphy (SRS) interpretation and clinical management of these tumors. Fourteen patients were included in the study. All patients underwent a whole body and SPECT-CT imaging with both (99m)Tc- EDDA/HYNIC-octreotate and (111)In-pentetrotide. Images were evaluated both visually and semiquantitatively. On patient basis, the diagnostic results of both studies were similar. The number of lesions detected by (99m)Tc- EDDA/HYNICOctreotate were higher than the number of lesions detected by (111)In-pentetrotide however the difference was not significant (40/43( 93%), 36/43 (83%) p=0.109). Semiquantitative analysis showed higher tumor/organ count ratios for both whole-body and SPECT (99m)Tc- EDDA/HYNIC-Octreotate scans. The results of this study suggested that, (99m)Tc- EDDA/HYNIC-Octreotate may be a better alternative to (111)In- pentetrotide due to high image quality and lower radiation dose. SPECT/CT is a valuable tool for the assessment of neuroendocrine tumors by providing the precise anatomic localization of scintigraphic findings thus improving lesion detectability and characterization. None declared.

In vitro evaluation of (99m)Tc-EDDA/tricine-HYNIC-Q-Litorin in gastrin-releasing peptide receptor positive tumor cell lines.

PubMed

Yurt Lambrecht, Fatma; Durkan, Kübra; Ozgür, Aykut; Gündüz, Cumhur; Avcı, Cığır Biray; Susluer, Sunde Yılmaz

2013-05-01

Bombesin and its derivatives exhibit a high affinity for gastrin-releasing peptide receptor (GRPr), which is over-expressed in a variety of human cancers (prostate, pancreatic, lung, etc.). The aim of this study was to investigate the in vitro potential of the hydrazinonicotinamide (HYNIC)-Q-Litorin. (99m)Tc labeling was performed by using different co-ligands: tricine and ethylenediamine diacetic acid (EDDA). The radiochemical stability of radiolabeled peptide conjugates was checked at room temperature and in cysteine solution up to 24 h. The in vitro cell uptake of (99m)Tc-EDDA-HYNIC-Q-Litorin and (99m)Tc-tricine-HYNIC-Q-Litorin were evaluated on pancreatic tumor and control cell lines. Optimum specific activity and incubation time were determined for all the cell lines. The results showed that the cell uptake of the radiolabeled peptide conjugates in tumor cell lines were higher than in the control cell line. The findings of this study indicated the need for further development of in vivo study as a radiopharmaceutical for pancreatic tumor imaging.

Preclinical evaluation of [99mTc/EDDA/tricine/HYNIC0, 1-Nal3, Thr8]-octreotide as a new analogue in the detection of somatostatin-receptor-positive tumors.

PubMed

Gandomkar, Mostafa; Najafi, Reza; Shafiei, Mohammad; Mazidi, Mohammad; Ebrahimi, Sayed Esmaeil Sadat

2007-08-01

Radiolabeled somatostatin analogues are important tools for the in vivo localization and targeted radionuclide therapy of somatostatin-receptor-positive tumors. The aim of this study was to evaluate a new somatostatin analogue designed for the labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), 1-Nal(3), Thr(8)]-octreotide ([HYNIC]-NATE), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. Synthesis was preformed on a solid phase using a standard Fmoc strategy. Labeling with (99m)Tc was performed at 100 degrees C for 10 min using SnCl(2) as a reductant. Radiochemical analysis involved ITLC and high-performance liquid chromatography methods. Peptide conjugate affinity was determined in AR4-2J cell membranes. The internalization and externalization rates were studied in sstr(2)-expressing AR4-2J cells. Biodistribution of radiopeptide was studied in rats bearing the AR4-2J tumor. Radiolabeling was performed at high specific activities, and radiochemical purity was >95%. Peptide conjugate showed high affinity binding for sstr(2). The radioligand showed a moderate and specific internalization into AR4-2J cells (14.13+/-0.61% at 4 h). In animal biodistribution studies, a receptor-specific uptake of radioactivity was observed in somatostatin-receptor-positive organs. After 4 h, uptake in the AR4-2J tumor was 1.33+/-0.23%ID/g (percentage of injected dose per gram of tissue). These data show that [(99m)Tc/EDDA/tricine/HYNIC]-NATE is a specific radioligand for the somatostatin-receptor-positive tumors and is a suitable candidate for clinical studies.

Specificity and sensitivity of ⁹⁹mTc-EDDA/HYNIC-Tyr³-octreotide (⁹⁹mTc-TOC) for imaging neuroendocrine tumors.

PubMed

Sepúlveda-Méndez, Jesús; de Murphy, Consuelo Arteaga; Pedraza-López, Martha; Murphy-Stack, Eduardo; Rojas-Bautista, Juan Carlos; González-Treviño, Ofelia

2012-01-01

Gastroenteropancreatic neuroendocrine tumors (NETs) are cancers originating from neuroendocrine organs such as the pancreas, pituitary, thyroid, and adrenal glands and tumors arising from the diffuse neuroendocrine cells that are widely distributed throughout the body. NETs express somatostatin (SS) and contain a high density of SS receptors; therefore, they can be specifically targeted with SS-based radiopharmaceuticals. The aim of this research was to determine the validity in terms of specificity, sensitivity, and the agreement beyond chance with the biopsy (gold standard) of the ⁹⁹mTc-EDDA-HYNIC-Tyr³octreotide (⁹⁹mTc-TOC) to image and localize NETs and their metastases. Freeze-dried kits containing 0.0125 mg HYNIC-octreotide and co-ligands were easily labeled and quality controlled within the hospital radiopharmacy. Fifty-six consecutive Mexican patients with a previous presumptive diagnosis of NETs underwent several clinical and laboratory studies and were referred to the Nuclear Medicine Department for a routine scan with ⁹⁹mTc-TOC. The patients were injected with 500-600 MBq ⁹⁹mTc-TOC, and whole-body images were obtained 2 h later with a SPECT or a SPECT/CT camera. Two nuclear medicine physicians observed the images and classified them as 17 negative and 39 positive. After correlating the image of each patient with our 'gold standard' (biopsy, clinical history, morphological images, and tumor marker assays), the ⁹⁹mTc-TOC images were classified by the same two physicians as 12 true negatives, five false negatives, 38 true positives and one false positive. The validity of ⁹⁹mTc-TOC in terms of relative frequencies with corresponding 95% confidence intervals were as follows: 92.3% (64-100%) specificity; 88.4% (78-97%) sensitivity; and the agreement beyond chance was 73% (60-84%). The positive predictive value was 97.4% (87-100%); the negative predicted value was 70.6% (48-93%); the accuracy was 89.3% (89-97%); and the prevalence was 76

Labeling and Biological Evaluation of (99m)Tc-HYNIC-Trastuzumab as a Potential Radiopharmaceutical for In Vivo Evaluation of HER2 Expression in Breast Cancer.

PubMed

Calzada, Victoria; Garcia, Fernanda; Fernández, Marcelo; Porcal, Williams; Quinn, Thomas; Alonso, Omar; Gambini, Juan Pablo; Cabral, Pablo

2013-01-01

The amplification of HER2 gene has been described in several tumor types, mainly breast cancer with a subsequent increase in HER2 protein expression. Trastuzumab is a humanized monoclonal antibody that recognizes selectively the HER2 extracellular domain. The objective of the present work was to standardize the conjugation of Trastuzumab with Succinimidyl-hydrazinonicotinamide (HYNIC) and labeling with (99m)Tc to obtain (99m)Tc-HYNIC-Trastuzumab for use as in vivo tracer of the HER2 expression in breast cancer. The labeling procedure involved derivatization of 0.067 μmol of Trastuzumab with 0.33 μmols of HYNIC in dimethyl sulfoxide (DMSO). The mixture was incubated for 30 min. A mixture of Tricine and SnCl2.2H2O was prepared by add a solution of 44.6 μmols Tricine in 0.05 mL HCl 2.0 M and a similar volume of another solution containing 44.3 μmols SnCl2.2H2O in 0.5 mL HCl 2.0 M. Then, 0.05 mL of this mixed was added to the conjugated with 296 MBq of 99mTcO-4. The final mixture was incubated at room temperature (18-25°C) for 30 min. Radiochemical purity of the labeled solution was studied by chromatography, to evaluate (99m)Tc-Tricine, (99m)TcO2.H2O, and free (99m)TcO4 (-). Radiochemical purity was also evaluated by HPLC. Stability studies were tested in solution at 4°C and lyophilized at 4°C. Biodistribution studies were performed in healthy CD-1 female mice at 2, 5, and 24 h (n = 3) and CD-1 female mice spontaneous breast adenocarcinoma (n = 3). Scintigraphic images of spontaneous breast adenocarcinoma in female CD-1 mice were acquired in a gamma camera at 2, 5, and 24 h post-injection. Labeling was easily performed with high yields (>90%) and radiopharmaceutical stability for 24 h post-labeling. Stability studies revealed that antibody derivative must be lyophilized for undamaged storage. Biodistribution studies and imaging revealed excellent uptake in the tumor. Based on the results it was concluded that (99m)Tc-HYNIC-Trastuzumab could be a promising

Influence of PET/CT 68Ga somatostatin receptor imaging on proceeding with patients, who were previously diagnosed with 99mTc-EDDA/HYNIC-TOC SPECT.

PubMed

Madrzak, Dorota; Mikołajczak, Renata; Kamiński, Grzegorz

2016-01-01

The aim of this study was the assessment of utility of somatostatin receptor scintigraphy (SRS) by SPECT imaging using 99mTc-EDDA/HYNIC-Tyr3-octreotide (99mTc-EDDA/HYNIC-TOC) in patients with neuroendocrine neoplasm (NEN) or suspected NEN, referred to Nuclear Medicine Dept. of Voivodship Specialty Center in Rzeszow. The selected group of patients was referred also to 68Ga PET/CT. The posed question was the ratio of patients for whom PET/CT with 68Ga would change their management. The distribution of somatostatin receptors was imaged using 99mTc-EDDA/HYNIC-TOC in 61 planar and SPECT studies between 13/05/2010 and 04/02/2013 in Nuclear Medicine Dept. of Voivodship Specialty Center in Rzeszow. The patient age was within a range of 17-80, with the average age of 57.6. The average age of women (65% of patients over-all) was 55.6 and the average age of men (35% of patients overall) was 61.4. In 46 participants (75% of the study group), that underwent SRS, NEN was documented using pathology tests. Selected patients were referred to PET/CT with 68Ga labeled somatostatin analogs, DOTATATE or DOTANOC. This study group consisted of 14 female and 10 male participants with age range of 35-77 and average age of 55.5 years. Patients were classified into 3 groups, as follows: detection - referral due to clinical symptoms and/or biochemical markers (CgA-Chromogranin A, IAA-indoleacetic acid) with the aim of primary diagnosis, staging - referral with the aim of assessment of tumor spread, and follow-up - assessment of the therapy. Out of 61 patients, 24 underwent both 99mTc-EDDA/HYNIC-Tyr3-octreotide SPECT and 68Ga PET/CT. The result of PET/CT was used as a basis for further evaluation. Therefore, the patients were divided into groups; true positive TP (confirmed presence of tissue somatostatin receptors with 68Ga PET/CT) and TN (68Ga PET/CT did not detect any changes and the results were comparable and had the same influence on treatment protocol). In case of SPECT, the results

Breast tumor targeting with (99m)Tc-HYNIC-PR81 complex as a new biologic radiopharmaceutical.

PubMed

Salouti, Mojtaba; Rajabi, Hossein; Babaei, Mohammad Hossein; Rasaee, Mohammad Javad

2008-10-01

Human epithelial mucin, MUC1, is commonly overexpressed in adenocarcinoma that includes more than 80% of breast cancers. The PR81 is a murine anti-MUC1 monoclonal antibody (MAb) that was prepared against the human breast cancer. We developed an indirect method for labeling of this antibody with (99m)Tc in order to use the new preparation in immunoscintigraphy studies of BALB/c mice bearing breast tumors. The (99m)Tc-PR81 complex was prepared using the HYNIC as a chelator and tricine as a coligand. The labeling efficiency determined by instant thin-layer chromatography (ITLC) was 89.2%+/-4.7%, and radiocolloides measured by cellulose nitrate electrophoresis were 3.4%+/-0.9%. The in vitro stability of labeled product was determined at room temperature by ITLC and in human serum by gel filtration chromatography - 88.3%+/-4.6% and 79.8%+/-5.7% over 24 h, respectively. The integrity of labeled MAb was checked by means of sodium dodecyl sulfate polyacrylamide gel electrophoresis, and no significant fragmentation was seen. The results of cell binding studies showed that both labeled and unlabeled PR81 were able to compete for binding to MCF 7 cells. Biodistribution studies performed in female BALB/c mice with breast tumor xenografts at 4, 16 and 24 h after the (99m)Tc-HYNIC-PR81 injection demonstrated a specific localization of the compound at the site of tumors and minimum accumulation in non target organs. The tumor imaging was performed in BALB/c mice with breast xenograft tumors at 4, 8, 12, 16, 20, 24, 28, 32 and 36 h after the complex injection. The tumors were visualized with high sensitivity after 8 h. The findings showed that the new radiopharmaceutical is a promising candidate for radioimmunoscintigraphy of the human breast cancer.

Clinical usefulness of 99mTc-EDDA/HYNIC-TOC scintigraphy in oncological diagnostics: a pilot study.

PubMed

Plachcinska, Anna; Mikolajczak, Renata; Maecke, Helmut; Mlodkowska, Ewa; Kunert-Radek, Jolanta; Michalski, Andrzej; Rzeszutek, Katarzyna; Kozak, Jozek; Kusmierek, Jacek

2004-04-01

The clinical usefulness of a new 99mTc-labeled somatostatin analogue has been studied from the standpoint of oncological diagnostics. The group of patients studied included 40 individuals with diagnosed malignant neoplasms (32 primary and 8 metastatic). Among the primary tumors were 7 pituitary adenomas (5 hormonally active and 2 inactive), 1 liposarcoma, 2 carcinoids, 1 breast carcinoma, and 21 cases of lung cancer (2 small cell and 19 non-small cell) were represented. The metastatic tumors consisted of: 3 malignant melanomas, 1 pheochromocytoma, 1 prostatic cancer, 1 leiomyosarcoma, 1 pancreatic carcinoma ectopically secreting ACTH, and 1 carcinoid of the thymus. The radiopharmaceutical, 99mTc-EDDA/HYNIC-octreotide, was i.v. administered at the activity of 740-925 MBq. The imaging was comprized of a whole-body scan and single photon emission computed tomography. Positive scintigrams were obtained in 4 of 5 hormonally active pituitary adenomas, in 1 of 2 cases of carcinoid, in liposarcoma, breast cancer, and all cases of small cell (SCLC) and non-small cell lung cancer (NSCLC). The neoplastic metastases were visualized in 2 of 3 cases of melanoma and in patients with pheochromocytoma, pancreatic carcinoma secreting ACTH, and thymic carcinoid. Scintigrams were negative in both hormonally inactive pituitary adenomas, in one case of metastatic malignant melanoma, leiomyosarcoma, and in cases of metastasis from the prostatic carcinomas. The results of this pilot study indicated that 99mTc-EDDA/HYNIC-TOC is a potentially useful radiopharmaceutical for the imaging of a wide range of primary and metastatic tumors. More detailed indications for the clinical usefulness of the new tracer for the imaging of selected tumor types require studies on much larger groups of patients. Special attention should be paid to the successful imaging of all cases of NSCLC.

Radio-guided surgery with the use of [99mTc-EDDA/HYNIC]octreotate in intra-operative detection of neuroendocrine tumours of the gastrointestinal tract.

PubMed

Hubalewska-Dydejczyk, A; Kulig, J; Szybinski, P; Mikolajczak, R; Pach, D; Sowa-Staszczak, A; Fröss-Baron, K; Huszno, B

2007-10-01

Radio-guided surgery (RGS) is an intra-operative localising technique which enables identification of tissue "marked" by a specific radiotracer injected before surgery. It is mainly used for sentinel node mapping and for detection of parathyroid adenomas and other tumours, including neuroendocrine tumours of the gastrointestinal tract (GEP-NET). The aim of this study was to determine whether intra-operative radio-detection with the use of [(99m)Tc-EDDA/HYNIC]octreotate, a new somatostatin analogue, is able to reveal an unknown primary and secondary sites, thereby improving surgical treatment and the final outcome of GEP-NET. The study group included nine patients with suspected GEP-NET (four carcinoids, five pancreatic NET) localised with somatostatin receptor scintigraphy (with [(99m)Tc-EDDA/HYNIC]octreotate), who had negative results on other pre-operative imaging tests. At surgery, suspected tumours were measured in situ and ex vivo and precise exploration of the abdominal cavity was performed with the intra-operative scintillation detector (Navigator). Intra-operative gamma counting localised three carcinoids. In one patient SRS was false positive (owing to inflammatory infiltration). Compared with SRS, RGS revealed additional lymph node metastases in one case. RGS resulted in successful localisation of all pancreatic NET (the smallest lesion was 8 mm in diameter). [(99m)Tc-EDDA/HYNIC]octreotate SRS followed by RGS is a promising technique to improve the rate of detection and efficacy of treatment of GEP-NET, especially in the presence of occult endocrine tumours. The imaging properties of [(99m)Tc-EDDA/HYNIC]octreotate and the 1-day imaging protocol offer opportunities for more widespread application of this tracer followed by RGS in oncology.

Design and evaluation of new Tc-99m-labeled lactam bridge-cyclized alpha-MSH peptides for melanoma imaging.

PubMed

Guo, Haixun; Gallazzi, Fabio; Miao, Yubin

2013-04-01

The purpose of this study was to examine the melanoma targeting and imaging properties of new (99m)Tc-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (α-MSH) peptides using bifunctional chelating agents. MAG3-GGNle-CycMSH(hex), AcCG3-GGNle-CycMSH(hex), and HYNIC-GGNle-CycMSH(hex) peptides were synthesized, and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution of (99m)Tc-MAG3-GGNle-CycMSH(hex), (99m)Tc-AcCG3-GGNle-CycMSH(hex), (99m)Tc(CO)3-HYNIC-GGNle-CycMSH(hex), and (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) were determined in B16/F1 melanoma-bearing C57 mice at 2 h postinjection to select a lead peptide for further evaluation. The melanoma targeting and imaging properties of (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) were further examined because of its high melanoma uptake and fast urinary clearance. The IC50 values of MAG3-GGNle-CycMSH(hex), AcCG3-GGNle-CycMSH(hex), and HYNIC-GGNle-CycMSH(hex) were 1.0 ± 0.05, 1.2 ± 0.19, and 0.6 ± 0.04 nM in B16/F1 melanoma cells, respectively. Among these four (99m)Tc-peptides, (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) exhibited the highest melanoma uptake (14.14 ± 4.90% ID/g) and fastest urinary clearance (91.26 ± 1.96% ID) at 2 h postinjection. (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) showed high tumor to normal organ uptake ratios except for the kidneys. The tumor/kidney uptake ratios of (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) were 2.50 and 3.55 at 4 and 24 h postinjection. The melanoma lesions were clearly visualized by SPECT/CT using (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) as an imaging probe at 2 h postinjection. Overall, high melanoma uptake coupled with fast urinary clearance of (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) highlighted its potential for metastatic melanoma detection in the future.

Design and Evaluation of New Tc-99m-Labeled Lactam Bridge-Cyclized Alpha-MSH Peptides for Melanoma Imaging

PubMed Central

Guo, Haixun; Gallazzi, Fabio; Miao, Yubin

2013-01-01

The purpose of this study was to examine the melanoma targeting and imaging properties of new 99mTc-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (α-MSH) peptides using bifunctional chelating agents. MAG3-GGNle-CycMSHhex, AcCG3-GGNle-CycMSHhex and HYNIC-GGNle-CycMSHhex peptides were synthesized and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution of 99mTc-MAG3-GGNle-CycMSHhex, 99mTc-AcCG3-GGNle-CycMSHhex, 99mTc(CO)3-HYNIC-GGNle-CycMSHhex and 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex were determined in B16/F1 melanoma-bearing C57 mice at 2 h post-injection to select a lead peptide for further evaluation. The melanoma targeting and imaging properties of 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex were further examined because of its high melanoma uptake and fast urinary clearance. The IC50 values of MAG3-GGNle-CycMSHhex, AcCG3-GGNle-CycMSHhex and HYNIC-GGNle-CycMSHhex were 1.0 ± 0.05, 1.2 ± 0.19 and 0.6 ± 0.04 nM in B16/F1 melanoma cells, respectively. Among these four 99mTc-peptides, 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex exhibited the highest melanoma uptake (14.14 ± 4.90% ID/g) and fastest urinary clearance (91.26 ± 1.96% ID) at 2 h post-injection. 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex showed high tumor to normal organ uptake ratios except for the kidneys. The tumor/kidney uptake ratios of 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex were 2.50 and 3.55 at 4 and 24 h post-injection. The melanoma lesions were clearly visualized by SPECT/CT using 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex as an imaging probe at 2 h post-injection. Overall, high melanoma uptake coupled with fast urinary clearance of 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex highlighted its potential for metastatic melanoma detection in the future. PMID:23418722

(99m)Tc HYNIC-TOC imaging and 177Lu DOTA-octreotate treatment in non-iodine-concentrating dedifferentiated thyroid carcinoma metastases: an unusual alternative diagnosis.

PubMed

Basu, Sandip; Joshi, Amit

2014-07-01

The value of Tc HYNIC-TOC scintigraphy clarifying skeletal and hepatic-predominant metastatic disease in a 55-year-old woman (diagnosed earlier to have papillary carcinoma thyroid and had undergone total thyroidectomy and radioiodine ablation) is illustrated. The whole-body radioiodine scan and battery of serum tumor markers were normal. Multiple metastatic foci in the liver and skeleton were Tc HYNIC-TOC avid. Serum chromogranin A level was substantially elevated (1771.60 ng/mL). This represents an unusual alternative diagnosis signified by a highly positive scan in the setting of apparent non-iodine-concentrating metastatic disease in a patient of differentiated thyroid carcinoma.

99mTc-EDDA/HYNIC-TOC somatostatin receptor scintigraphy in daily clinical practice.

PubMed

Chrapko, Beata Ewa; Nocuń, Anna; Gołebiewska, Renata; Stefaniak, Bogusław; Korobowicz, Elzbieta; Czekajska-Chehab, Elzbieta; Sawicki, Marek; Polkowski, Wojciech Piotr

2010-04-01

This study aimed to assess the impact of 99mTc-EDDA/HYNIC-TOC (99mTc-TOC) somatostatin receptor scintigraphy (SRS) in clinical practice. One hundred seventeen patients were divided into 6 groups: 1, initial detection and localization of suspected neuroendocrine tumor (NET); 2, tumor staging before therapy; 3, staging of NET of unknown origin, 4, restaging after surgery of primary tumor; 5, diagnosis of solitary pulmonary nodules (SPNs), and 6, follow-up after "cold" somatostatin analogues treatment. In group 1, clinical suspicions were not confirmed in any of the patients; in group 2, most of the primary lesions showed overexpression of somatostatin receptors (SSRT); in group 3, the primary tumor was not identified in any of the patients; in group 4, recurrences were depicted in 7 out of 47 patients; in group 5, only 1 malignant SPN was detected, and in group 6, regression of primary mass and metastases were seen on follow-up SRS in 1 patient. 99mTc-TOC SRS is useful in staging of SSRT-overexpressing tumors of known and unknown primary origin, as well as in restaging after primary tumor surgery. This method is less effective in detecting suspected NET and assessing SPNs. Further investigation is necessary to evaluate the usefulness of SRS in monitoring patients after biological treatment.

Evaluation of neuroendocrine tumors with 99mTc-EDDA/HYNIC TOC.

PubMed

Artiko, Vera; Afgan, Aida; Petrović, Jelena; Radović, Branislava; Petrović, Nebojša; Vlajković, Marina; Šobić-Šaranović, Dragana; Obradović, Vladimir

2016-01-01

This paper is the short review of our preliminary results obtained with 99mTc-EDDA/HYNIC-TOC. The total of 495 patients with different neuroendocrine tumors were investigated during last few years. There have been 334 true positive (TP), 73 true negative (TN), 6 false positive (FP) and 82 false negative findings (FN). Diagnosis was made according to SPECT findings in 122 patients (25%). The mean T/NT ratio for TP cases was significantly higher (p < 0.01) on SPECT (3.12 ± 1.13) than on whole body scan (2.2 ± 0.75). According to our results, overall sensitivity of the method is 80%, specificity 92%, positive predictive value 98%, negative predictive value 47% and accuracy 82%. Fifteen TP patients underwent therapy with 90Y-DOTATATE. Scintigraphy of neuroendocrine tumors with 99mTc-Tektrotyd is a useful method for diagnosis, staging and follow up of the patients suspected to have neuroendocrine tumors. SPECT had important role in diagnosis. It is also helpful in the appropriate choice of the therapy, including the peptide receptor radionuclide therapy. In the absence of 68Ga-labeled peptides and PET/CT, the special emphasize should be given to application of SPECT/CT as well as to the radioguided surgery.

Bombesin receptors and transplanted stem cells in rat brain: High-resolution scan with 99mTc BN1.1

NASA Astrophysics Data System (ADS)

Scopinaro, F.; Paschali, E.; Di Santo, G.; Antonellis, T.; Massari, R.; Trotta, C.; Gourni, H.; Bouziotis, P.; David, V.; Soluri, A.; Varvarigou, A. D.

2006-12-01

The aim of this work is to detect the presence of transplanted stem cells (TSC) in rat brain with high-resolution (HR) scintigraphy and labelled bombesin (BN). BN is a morphogen for Central Nervous System (CNS) as well as for other organs: CNS-oriented TSC over-express BN Receptors (BNR). BN is also a neurotransmitter and modulates several functions of CNS. 99mTc labelled BN-like peptide scan of CNS is the ideal method to detect growing TSC once knowing normal distribution of BNRs in CNS. HR Planar and single photon emission computerized tomography (SPECT) images of rat brain were performed with new HR detectors (Li-tech, Italy). Pertechnetate, 99mTc HMPAO and the new 99mTc BN1.1 (patented) were i.v. administered in five rats. HR SPECT of 99mTc BN1.1 detected olfactory tract, fronto-lateral cortex, cerebellum, basal ganglia and amygdale. Results of SPECT were confirmed by bio-distribution study performed after autopsy of three of the five rats. The remaining two rats underwent cerebral lesions followed by transplant of TSC. Three months later, HR scintigraphy was repeated and showed images completely different from previous basal study, with hot spot of 99mTc BN1.1 corresponding to the site of TSC transplant. Immuno-histochemistry confirmed the presence of viable TSC. Not only 99mTc BN1.1 HR scan showed viability of transplanted TSC but also the "background brain" was the still now unknown map of BNR in mammalian brain.

Efficacy of (99m)Tc-EDDA/HYNIC-TOC SPECT/CT scintigraphy in Graves' ophthalmopathy.

PubMed

Zhao, Rong; Wang, Jiang; Deng, Jinglan; Yang, Weidong; Wang, Jing

2012-01-01

The aim of this study was to investigate the predictive role of the orbital somatostatin receptor scintigraphy with (99m)Tc-EDDA/HYNIC-TOC ((99m)Tc-TOC) to detect clinical stage of Graves' ophthalmopathy and the response to corticosteroid therapy. The subjects of the experiment were 46 patients with Graves' ophthalmopathy (GO) and four volunteers without eye disease or GO as the normal group (NG). Single photon emission computed tomography (SPECT), computed tomography (CT) and the left and right lateral position planar imaging of the heads of the all subjects were obtained 4 h after the intravenous injection of 555 MBq of (99m)Tc-TOC. The (99m)Tc-TOC SPECT/CT was repeated 3 months later. 35 (35/46) patients were received corticosteroid therapy (prednisolone, 10 mg po tid ) for 3 months, however, the other 11 patients as control groups did not receive any treatment. The treatment effect was evaluated both by the orbital (99m)Tc-TOC uptake and NOSPECS. A significant decrease in the O/OC ratio was observed in 22 GO patients between pre- and post-treatment (1.64 ± 0.13 vs. 1.21 ± 0.09, P < 0.05). There were neither significant difference of the O/OC ratio in 13 GO patients between pre- and post-treatment periods, nor significant difference in the 9 (9/11) patients before and after three months. Orbital (99m)Tc-TOC scintigraphy is a feasible technique to estimate the Graves' ophthalmopathy activity and predict the response to subsequent corticosteroid therapy in GO patients. The technique could be a useful tool for physicians not familiar with CAS determination.

Efficacy of 99mTc-EDDA/HYNIC-TOC SPECT/CT scintigraphy in Graves’ ophthalmopathy

PubMed Central

Zhao, Rong; Wang, Jiang; Deng, Jinglan; Yang, Weidong; Wang, Jing

2012-01-01

The aim of this study was to investigate the predictive role of the orbital somatostatin receptor scintigraphy with 99mTc-EDDA/HYNIC-TOC (99mTc-TOC) to detect clinical stage of Graves’ ophthalmopathy and the response to corticosteroid therapy. The subjects of the experiment were 46 patients with Graves’ ophthalmopathy (GO) and four volunteers without eye disease or GO as the normal group (NG). Single photon emission computed tomography (SPECT), computed tomography (CT) and the left and right lateral position planar imaging of the heads of the all subjects were obtained 4 h after the intravenous injection of 555 MBq of 99mTc-TOC. The 99mTc-TOC SPECT/CT was repeated 3 months later. 35 (35/46) patients were received corticosteroid therapy (prednisolone, 10 mg po tid ) for 3 months, however, the other 11 patients as control groups did not receive any treatment. The treatment effect was evaluated both by the orbital 99mTc-TOC uptake and NOSPECS. A significant decrease in the O/OC ratio was observed in 22 GO patients between pre- and post-treatment (1.64 ± 0.13 vs. 1.21 ± 0.09, P < 0.05). There were neither significant difference of the O/OC ratio in 13 GO patients between pre- and post-treatment periods, nor significant difference in the 9 (9/11) patients before and after three months. Orbital 99mTc-TOC scintigraphy is a feasible technique to estimate the Graves’ ophthalmopathy activity and predict the response to subsequent corticosteroid therapy in GO patients. The technique could be a useful tool for physicians not familiar with CAS determination. PMID:23133815

Utility of 99mTc-Hynic-TOC in 131I Whole-Body Scan Negative Thyroid Cancer Patients with Elevated Serum Thyroglobulin Levels

PubMed Central

Shinto, Ajit S.; Kamaleshwaran, K. K.; Mallia, Madhav; Korde, Aruna; Samuel, Grace; Banerjee, Sharmila; Velayutham, Pavanasam; Damodharan, Suresh; Sairam, Madhu

2015-01-01

Several studies have reported on the expression of somatostatin receptors (SSTRs) in patients with differentiated thyroid cancer (DTC). The aim of this study was to evaluate the imaging abilities of a recently developed Technetium-99m labeled somatostatin analog, 99mTc-Hynic-TOC, in terms of precise localization of the disease. The study population consisted of 28 patients (16 men, 12 women; age range: 39-72 years) with histologically confirmed DTC, who presented with recurrent or persistent disease as indicated by elevated serum thyroglobulin (Tg) levels after initial treatment (serum Tg > 10 ng/ml off T4 suppression for 4-6 weeks). All patients were negative on the Iodine-131 posttherapy whole-body scans. Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) was performed in all patients. SSTR scintigraphy was true positive in 23 cases (82.1%), true negative in two cases (7.1%) and false negative in three cases (10.7%) which resulted in a sensitivity of 88.46%, specificity of 100% and an accuracy of 89.2%. Sensitivity of 99mTc-Hynic-TOC scan was higher (93.7%) for patients with advanced stages, that is stages III and IV. 18F-FDG showed a sensitivity of 93.7%, a specificity of 50% and an accuracy of 89.3%. 18F-FDG PET was found to be more sensitive, with lower specificity due to false positive results in 2 patients. Analysis on a lesion basis demonstrated substantial agreement between the two imaging techniques with a Cohen's kappa of 0.66. Scintigraphy with 99mTc-Hynic-TOC might be a promising tool for treatment planning; it is easy to perform and showed sufficient accuracy for localization diagnostics in thyroid cancer patients with recurrent or metastatic disease. PMID:26097420

Utility of (99m)Tc-Hynic-TOC in 131I Whole-Body Scan Negative Thyroid Cancer Patients with Elevated Serum Thyroglobulin Levels.

PubMed

Shinto, Ajit S; Kamaleshwaran, K K; Mallia, Madhav; Korde, Aruna; Samuel, Grace; Banerjee, Sharmila; Velayutham, Pavanasam; Damodharan, Suresh; Sairam, Madhu

2015-01-01

Several studies have reported on the expression of somatostatin receptors (SSTRs) in patients with differentiated thyroid cancer (DTC). The aim of this study was to evaluate the imaging abilities of a recently developed Technetium-99m labeled somatostatin analog, (99m)Tc-Hynic-TOC, in terms of precise localization of the disease. The study population consisted of 28 patients (16 men, 12 women; age range: 39-72 years) with histologically confirmed DTC, who presented with recurrent or persistent disease as indicated by elevated serum thyroglobulin (Tg) levels after initial treatment (serum Tg > 10 ng/ml off T4 suppression for 4-6 weeks). All patients were negative on the Iodine-131 posttherapy whole-body scans. Fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) was performed in all patients. SSTR scintigraphy was true positive in 23 cases (82.1%), true negative in two cases (7.1%) and false negative in three cases (10.7%) which resulted in a sensitivity of 88.46%, specificity of 100% and an accuracy of 89.2%. Sensitivity of (99m)Tc-Hynic-TOC scan was higher (93.7%) for patients with advanced stages, that is stages III and IV. (18)F-FDG showed a sensitivity of 93.7%, a specificity of 50% and an accuracy of 89.3%. (18)F-FDG PET was found to be more sensitive, with lower specificity due to false positive results in 2 patients. Analysis on a lesion basis demonstrated substantial agreement between the two imaging techniques with a Cohen's kappa of 0.66. Scintigraphy with (99m)Tc-Hynic-TOC might be a promising tool for treatment planning; it is easy to perform and showed sufficient accuracy for localization diagnostics in thyroid cancer patients with recurrent or metastatic disease.

Efficacy of 99mTc-EDDA/HYNIC-TOC scintigraphy in differential diagnosis of solitary pulmonary nodules.

PubMed

Płachcińska, Anna; Mikołajczak, Renata; Maecke, Helmut; Kozak, Józef; Michalski, Andrzej; Rzeszutek, Katarzyna; Kuśmierek, Jacek

2004-10-01

Fifty consecutive patients with solitary pulmonary nodules (SPN) on chest radiographs were studied scintigraphically after the administration of a somatostatin analog 99mTc-EDDA/HYNIC-TOC. The activity amounted to 740-925 MBq and a single photon emission computed tomography (SPECT) technique was applied. Verification of the nodule etiology was based on histology or cytology and bacteriology. As additional criterion for nodule benignity, its stable size in a chest radiograph for at least 3 years was accepted. In 31 patients, malignant etiologies of nodules were found. The diagnoses included: 11 adenocarcinomas, 6 squamous-cell carcinomas, 2 large-cell carcinomas, 6 nonsmall-cell lung cancers (NSCLC) of unspecified, more detailed morphology, 2 small-cell lung cancers (SCLC), 2 typical carcinoids, and 2 metastatic tumors: leiomyosarcoma and malignant melanoma. In 19 patients, the following benign tumors were diagnosed: 6 tuberculomas, 2 other granulomas, 4 hamartomas, 2 nonspecific inflammatory infiltrates, 1 abscess, 1 peripheral carcinoid of morphological characteristics of a benign tumor, 1 ectopic lesion of thyroid tissue, and 2 benign tumors of unspecified etiology, with stable size over 3 and 5 years. Positive scintigraphic results were obtained in 28 of 31 patients (90%) with malignant SPNs; among these there were 26 of 27 (96%) cases of primary pulmonary carcinoma. The remaining 2 false-negative cases included metastatic tumors: liposarcoma and melanoma. Among 19 benign lesions, 15 (79%) did not accumulate the radiopharmaceutical. The remaining 4 tumors visible on scintigrams included: 1 tuberculoma, 1 hamartoma, 1 abscess, and 1 case of nonestablished diagnosis (with stable size over 3 years). In conclusion, scintigraphy with 99mTc-EDDA/HYNIC-TOC appears to be an effective procedure for differentiation between malignant and benign SPNs.

Clinical utility of indigenously formulated single-vial lyophilized HYNIC-TOC kit in evaluating Gastro-entero Pancreatic neuro endocrine tumours

PubMed Central

Shinto, Ajit S; Kamaleshwaran, K; Vyshak, K; Sudhakar, Natarajan; Banerjee, Sharmila; Korde, Aruna; Samuel, Grace; Mallia, Madhav

2014-01-01

Objective(s): The objective of this study was to evaluate the performance and utility of 99mTc HYNIC-TOC planar scintigraphy and SPECT/CT in the diagnosis, staging and management of gastroenteropancreatic neuroendocrine tumors (GPNETs). Methods: 22 patients (median age, 46 years) with histologically proven gastro- entero- pancreatic NETs underwent 99mTc HYNIC-TOC whole body scintigraphy and regional SPECT/CT as indicated. Scanning was performed after injection of 370-550 MBq (10-15 mCi) of 99mTc HYNIC-TOC intravenously. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as semi quantitatively (tumor to background and tumor to normal liver ratios on SPECT -CT images). Results of SPECT/CT were compared with the results of conventional imaging. Histopathology results and follow-up somatostatin receptor scintigraphy with 99mTc HYNIC TOC or conventional imaging with biochemical markers were considered to be the reference standards. Results: 99mTc HYNIC TOC showed sensitivity and specificity of 87.5% and 85.7%, respectively, for primary tumor and 100% and 86% for metastases. It was better than conventional imaging modalities for the detection of both primary tumor (P<0.001) and metastases (P<0.0001). It changed the management strategy in 6 patients (31.8%) and supported management decisions in 8 patients (36.3%). Conclusion: 99mTc HYNIC TOC SPECT/CT appears to be a highly sensitive and specific modality for the detection and staging of GPNETs. It is better than conventional imaging for the evaluation of GPNETs and can have a significant impact on patient management and planning further therapeutic options. PMID:27408857

Clinical utility of indigenously formulated single-vial lyophilized HYNIC-TOC kit in evaluating Gastro-entero Pancreatic neuro endocrine tumours.

PubMed

Shinto, Ajit S; Kamaleshwaran, K; Vyshak, K; Sudhakar, Natarajan; Banerjee, Sharmila; Korde, Aruna; Samuel, Grace; Mallia, Madhav

2014-01-01

The objective of this study was to evaluate the performance and utility of (99m)Tc HYNIC-TOC planar scintigraphy and SPECT/CT in the diagnosis, staging and management of gastroenteropancreatic neuroendocrine tumors (GPNETs). 22 patients (median age, 46 years) with histologically proven gastro- entero- pancreatic NETs underwent (99m)Tc HYNIC-TOC whole body scintigraphy and regional SPECT/CT as indicated. Scanning was performed after injection of 370-550 MBq (10-15 mCi) of (99m)Tc HYNIC-TOC intravenously. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as semi quantitatively (tumor to background and tumor to normal liver ratios on SPECT -CT images). Results of SPECT/CT were compared with the results of conventional imaging. Histopathology results and follow-up somatostatin receptor scintigraphy with (99m)Tc HYNIC TOC or conventional imaging with biochemical markers were considered to be the reference standards. (99m)Tc HYNIC TOC showed sensitivity and specificity of 87.5% and 85.7%, respectively, for primary tumor and 100% and 86% for metastases. It was better than conventional imaging modalities for the detection of both primary tumor (P<0.001) and metastases (P<0.0001). It changed the management strategy in 6 patients (31.8%) and supported management decisions in 8 patients (36.3%). (99m)Tc HYNIC TOC SPECT/CT appears to be a highly sensitive and specific modality for the detection and staging of GPNETs. It is better than conventional imaging for the evaluation of GPNETs and can have a significant impact on patient management and planning further therapeutic options.

Comparative assessment of a 99mTc labeled H1299.2-HYNIC peptide bearing two different co-ligands for tumor-targeted imaging.

PubMed

Torabizadeh, Seyedeh Atekeh; Abedi, Seyed Mohammad; Noaparast, Zohreh; Hosseinimehr, Seyed Jalal

2017-05-01

Peptides are a class of targeting agents that bind to cancer-specific cell surfaces. Since they specifically target cancer cells, they could be used as molecular imaging tools. In this study, the 15-mer peptide Ac-H1299.2 (YAAWPASGAWTGTAP) was conjugated with HYNIC via lysine amino acid on C-terminus and labeled with 99m Tc using tricine and EDDA/tricine as the co-ligands. These radiotracers were evaluated for potential utilization in diagnostic imaging of ovarian cancer cells (SKOV-3). The cell-specificity of these radiolabeled peptides was determined based on their binding on an ovarian cancer cell line (SKOV-3), and displaying a low affinity for lung adenocarcinoma cell line (A549) and breast cancer cell line (MCF7). Biodistribution studies were conducted in normal mice as well as in nude mice bearing SKOV-3 ovarian cancer xenografts. HYNIC-peptide was labeled with 99m Tc with more than 99% efficiency and showed high stability in buffer and serum. We observed nanomolar binding affinities for both radiolabeled peptides. The tumor uptakes were 3.27%±0.46% and 1.55%±0.20% for tricine and 2.34±1.1% and 1.09%±0.18% for EDDA/tricine at 1 and 4h after injection, respectively. A higher tumor to background ratio and lower radioactivity in the blood were observed for EDDA/tricine co-ligands, leading to clear tumor visualization in imaging with injection of this peptide. This new 99m Tc-labeled peptide selectively targeted ovarian cancer and introduction of a (EDDA/tricine) as a co-ligand improved the pharmacokinetics of 99m Tc-labeled H1299.2 for tumor imaging in animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Glomus Tumor of the Neck Detected With 99mTc EDDA HYNIC-TOC.

PubMed

Girotto, Neva; Bogović-Crnčić, Tatjana; Grbac-Ivanković, Svjetlana; Valković-Zujić, Petra

2017-10-01

A 54-year-old woman was referred to thyroid evaluation because of a lump on the left side of the neck. Ultrasound exam did not show any thyroid abnormality, but highly perfused nodule at the left common carotid artery bifurcation was found. Because of the specific location, somatostatin receptor scintigraphy with Tc EDDA HYNIC-TOC was performed, starting with perfusion images and followed with SPECT/CT imaging at 2 and 4 hours. Well-perfused nodule with intensive accumulation and no other visible pathology in the body raised suspicion of a glomus tumor, consistent with MR exam performed later. Subsequent surgical removal confirmed carotid paraganglioma.

99mTc-EDDA/HYNIC-TOC scintigraphy in the differential diagnosis of solitary pulmonary nodules.

PubMed

Płachcińska, Anna; Mikołajczak, Renata; Maecke, Helmut R; Michalski, Andrzej; Rzeszutek, Katarzyna; Kozak, Józef; Kuśmierek, Jacek

2004-07-01

Forty-three consecutive patients with solitary pulmonary nodules (SPNs) on chest radiographs were studied scintigraphically after administration of the somatostatin analogue (99m)Tc-EDDA/HYNIC-TOC. The objective of the study was to assess the usefulness of the procedure for differentiation of SPNs as malignant or benign. The administered activity was 740-925 MBq, and a single-photon emission computed tomography imaging technique was employed. Verification of the nodule aetiology was based on histology or cytology and bacteriology. A stable tumour size on chest radiography for at least 3 years was accepted as an additional criterion of benignity. In 29 patients, nodules were found to be malignant. The diagnoses included ten adenocarcinomas, five squamous cell carcinomas, two large cell carcinomas, six non-small cell lung cancers without specification of the more detailed morphology, two small cell lung cancers, two typical carcinoids and two metastatic tumours (leiomyosarcoma and malignant melanoma). In 14 patients the following benign tumours were diagnosed: four tuberculomas, one other granuloma, three hamartomas, one non-specific inflammatory infiltrate, one abscess, one peripheral carcinoid with the morphological characteristics of a benign tumour, one ectopic lesion of thyroid tissue and two benign tumours of unspecified aetiology with a stable size over 3 and 5 years respectively. Positive scintigraphic results were obtained in 26 of the 29 patients (90%) with malignant SPNs; among these, 24 of the 25 (96%) cases of primary pulmonary carcinoma yielded positive results. The remaining two false negative cases were the metastatic tumours, liposarcoma and melanoma. Of the 14 benign lesions, ten (71%) did not accumulate the radiopharmaceutical. The remaining four benign tumours that were visible on scintigrams comprised one tuberculoma, one hamartoma, one abscess and one case in which the diagnosis could not be established (the tumour had a stable size over 3 years

Clinical usefulness of 99mTc-EDDA/HYNIC-TOC scintigraphy in oncological diagnostics: a preliminary communication.

PubMed

Płachcińska, Anna; Mikołajczak, Renata; Maecke, Helmut R; Młodkowska, Ewa; Kunert-Radek, Jolanta; Michalski, Andrzej; Rzeszutek, Katarzyna; Kozak, Józef; Kuśmierek, Jacek

2003-10-01

This study assessed the clinical usefulness of a new technetium-99m labelled somatostatin analogue from the standpoint of oncological diagnostics. The study group comprised 40 patients in whom malignant neoplasms (32 primary and 8 metastatic) had been diagnosed. Among the primary tumours there were 21 cases of lung cancer (2 small cell and 19 non-small cell), seven pituitary adenomas (five hormonally active and two inactive), one liposarcoma, two carcinoids and one breast carcinoma. The metastatic tumours consisted of three malignant melanomas, one phaeochromocytoma, one prostatic cancer, one leiomyosarcoma, one pancreatic carcinoma ectopically secreting ACTH and one carcinoid of the thymus. The radiopharmaceutical 99mTc-EDDA/HYNIC-Tyr3-octreotide was administered i.v. at an activity of 740-925 MBq. The imaging comprised a whole-body scan and a single-photon emission tomography acquisition. Positive scintigrams were obtained in all cases of small cell and non-small cell lung cancer, four out of five hormonally active pituitary adenomas, one out of two cases of carcinoid, the liposarcoma and the breast cancer. Neoplastic metastases were visualised in two out of three patients with melanoma and in patients with phaeochromocytoma, ACTH-secreting pancreatic carcinoma and thymic carcinoid. Scintigrams were negative in both hormonally inactive pituitary adenomas, in one case of metastatic malignant melanoma, in the leiomyosarcoma and in the case of metastasis from prostatic carcinoma. The results of this pilot study indicate that 99mTc-EDDA/HYNIC-TOC is a potentially useful radiopharmaceutical for imaging of a wide range of primary and metastatic tumours. Special attention should be paid to the successful imaging of all cases of non-small cell lung cancer.

Initial direct comparison of 99mTc-TOC and 99mTc-TATE in identifying sites of disease in patients with proven GEP NETs.

PubMed

Cwikla, Jaroslaw B; Mikolajczak, Renata; Pawlak, Dariusz; Buscombe, John R; Nasierowska-Guttmejer, Anna; Bator, Andrzej; Maecke, Helmut R; Walecki, Jerzy

2008-07-01

The imaging of neuroendocrine tumors has become one of the most significant areas in nuclear oncology. In an attempt to provide high-quality imaging and possible sensitivity at a reduced cost, time, and radiation dose, several (99m)Tc agents have been proposed. The aim of this initial study was to compare the tumor uptake and biodistribution of 2 new 6-hydrazinopyridine-3-carboxylic acid (HYNIC)-derivatized Tyr(3)-octreotide analogs, (99m)Tc-[HYNIC,Tyr(3)]octreotide ((99m)Tc-TOC) and (99m)Tc-[HYNIC,Tyr(3),Thr(8)]octreotide ((99m)Tc-TATE), in patients with somatostatin receptor-expressing tumors. Each of 12 patients with proven gastrointestinal pancreatic neuroendocrine tumors received a mean activity of 520 MBq of (99m)Tc-TOC and (99m)Tc-TATE. Scintigraphy with both tracers was performed 3-4 h after their injection using standard whole-body and SPECT imaging. The images were reviewed subjectively by 2 readers, who reported tumor uptake lesion by lesion. Both radiotracers demonstrated concordance between the results in 7 patients (58%). In total, 110 sites of disease were identified with (99m)Tc-TOC, compared with 115 with (99m)Tc-TATE. There was 1 case in which (99m)Tc-TOC identified sites of disease not seen on (99m)Tc-TATE imaging but 4 cases in which some sites of disease were seen with (99m)Tc-TATE and not (99m)Tc-TOC. In this initial study, both tracers seem to show similar sites of tumor, with (99m)Tc-TATE having a slight edge in the total number of lesions seen, especially in lymph node metastases.

Synthesis and evaluation of (99m)Tc chelate-conjugated bevacizumab.

PubMed

Camacho, Ximena; García, María Fernanda; Calzada, Victoria; Fernández, Marcelo; Porcal, Williams; Alonso, Omar; Gambini, Juan Pablo; Cabral, Pablo

2013-03-01

Vascular endothelial growth factor (VEGF) is one of the classic factors involved in tumor-induced angiognesis in several solid tumors. Bevacizumab, a monoclonal antibody against VEGF, can be used as an imaging tool in preclinical studies. The aim of this study was to radiolabel Bevacizumab with (99m)Tc and to evaluate in vivo its imaging properties in an adenocarcinoma animal model. For this purpose, Bevacizumab was derivatized with Suc-HYNIC as a bifunctional coupling agent. A mixture of Tricine/SnCl(2).2H(2)O was added to Bevacizumab-HYNIC and radiolabeled with (99m)TcO(4)(-). The radiochemical stability of the radiolabeled antibody was assessed. Biodistribution and scintigraphy imaging were performed in normal CD1 female mice and in spontaneous adenocarcinoma tumor bearing CD1 mice (n = 5). We demonstrated that 99mTc-HYNIC-Bevacizumab was stable. In vivo biodistribution studies revealed that tumor uptake of (99m)Tc-HYNIC-Bevacizumab was 1.37 ± 0.51% and 5.33 ± 2.13% at 4 and 24 h postinjection, respectively. Scintigraphy image studies showed tumor selective uptake of (99m)Tc-HYNIC-Bevacizumab in the tumor-bearing mice. We conclude that (99m)Tc-HYNIC-Bevacizumb has the potential to be used as a tracer for tumor imaging in preclinical studies.

99mTc-EDDA/HYNIC-TOC in the diagnosis of differentiated thyroid carcinoma refractory to radioiodine treatment.

PubMed

Czepczyński, Rafał; Gryczyńska, Maria; Ruchała, Marek

2016-01-01

In majority of cases of differentiated thyroid carcinoma (DTC), the ablative radioiodine treatment shows high efficacy. In a small number of patients, mechanism of selective iodine uptake by the DTC cells is insufficient and alternative methods of diagnosis and treatment are needed. As demonstrated in vitro, DTC cells show expression of somatostatin recep-tors. Radiolabeled somatostatin analogs are widely used in the diagnosis of neuroendocrine tumors. The aim of the study was to evaluate the utility of peptide receptor scintigraphy with the use of 99mTc-EDDA/HYNIC-TOC in the diagnosis of DTC in patients with elevated thyroglobulin concentrations (Tg), negative WBS and no effect of the consecutive radioiodine therapies. Whole body scintigraphy as well as SPECT of neck and chest were performed 3 and 24 h after i.v. administration of 740 MBq 99mTc-EDDA/HYNIC-TOC. The obtained images were compared with other radionuclide and ra-diological imaging methods. Forty-three patients with DTC after surgery and ablative radioiodine treatment with negative WBS and elevated Tg were qualified. Patients' age: 18-83 years (mean 58.0). SRS showed foci of tracer accumulation in 29 cases (67.4%). Sensitivity was 69.0% specificity 78.6%. SRS correctly identified local recurrence in 8 pts., metastatic lymph nodes in 19 pts., lung metastases in 12 pts. and bone metastases in 5 pts. SRS showed high sensitivity in the detection of metastatic lymph nodes (100%) and bone metastases (83.3%) and lung metastases (63.2%). Positive SRS was found in pts. with higher Tg concentrations (130 ± 144 vs. 30 ± 54 ng/ml). Scintigraphy with the use of the studied technetium-99m-labeled somatostatin analog is useful in the evaluation of patients with advanced DTC. It shows relatively good sensitivity and specificity but not high enough to be recommended as a routine imaging method. The role of somatostatin receptor scintigraphy in DTC is complementary to other imaging modalities.

Synthesis and Biological Evaluation of Cyclic [99mTc]-HYNIC-CGPRPPC as a Fibrin-Binding Peptide for Molecular Imaging of Thrombosis and Its Comparison with [99mTc]-HYNIC-GPRPP.

PubMed

Rezaeianpour, Sedigheh; Bozorgi, Atefeh Hajiagha; Moghimi, Abolghasem; Almasi, Ameneh; Balalaie, Saeed; Ramezanpour, Sorour; Nasoohi, Sanaz; Mazidi, Seyed Mohammad; Geramifar, Parham; Bitarafan-Rajabi, Ahmad; Shahhosseini, Soraya

2017-04-01

Many patients worldwide suffer from cardiovascular diseases for which an underlying factor is thrombosis. Devising a molecular imaging technique for early detection of thrombosis in a clinical setting is highly recommended. Because fibrin is a major constituent of clots and is present in all types of thrombi but absent in circulation, it is a highly specific and sensitive target for molecular imaging of thrombi. It is assumed that cyclization of peptides will improve the receptor binding affinity and stability of the peptide. In the present study, we have developed linear and cyclic fibrin-binding peptides for thrombus imaging and compared their biological properties. Linear HYNIC-GPRPP and cyclic HYNIC-CGPRPPC peptides were synthesized using a standard Fmoc strategy and radiolabeled with Tc-99m. The stability of the radiolabeled peptides in human plasma and their affinity for fibrin and blood clots were determined. Blood clearance and biodistribution were evaluated in rats and mice, respectively. The peptide with the highest affinity was injected to a live rabbit femoral thrombosis model, and scintigraphic images were obtained. In vitro studies show that peptides are stable in human plasma and have a high affinity for human fibrin. They also demonstrated fast blood clearance in rats and high thrombus uptake in the Balb/c mice femoral thrombosis model. Femoral thrombosis was visualized 30 min postinjection of cyclic peptide in a live rabbit model using single photon emission computed tomography (SPECT)/X-ray computed tomography. The results indicate that the cyclic peptide is a promising agent for molecular imaging of fibrin using SPECT.

Unicentric Castleman's Disease Revealed by 18F-FDG PET/CT and Somatostatin Receptor Scintigraphy With 99mTc-HYNIC-TOC.

PubMed

Luo, Yaping; Wang, Ling; Pan, Qingqing; Ma, Yanru; Li, Fang

2018-07-01

A 51-year-old woman with a history of hypertension and abdominal pain was found with a retroperitoneal mass. The mass had intense enhancement in contrast-enhanced CT, and it showed a moderate degree of increased FDG uptake in PET/CT. The mass was also positive in somatostatin receptor scintigraphy with Tc-HYNIC-TOC, but it was negative in I-MIBG scan. The histopathological result after surgical resection of the mass confirmed the diagnosis of Castleman's disease, the hyaline vascular variant.

Synthesis and antimicrobial evaluation of two peptide LyeTx I derivatives modified with the chelating agent HYNIC for radiolabeling with technetium-99m.

PubMed

Fuscaldi, Leonardo Lima; Dos Santos, Daniel Moreira; Pinheiro, Natália Gabriela Silva; Araújo, Raquel Silva; de Barros, André Luís Branco; Resende, Jarbas Magalhães; Fernandes, Simone Odília Antunes; de Lima, Maria Elena; Cardoso, Valbert Nascimento

2016-01-01

with (99m)Tc. The radiochemical purity analysis of LyeTx I-K-HYNIC-(99m)Tc showed that the optimal radiolabeling conditions (10 μg of LyeTx I-K-HYNIC; 250 μg of SnCl2 (.) 2H2O; pH = 7; heating for 15 min) yielded a radiochemical purity of 87 ± 1 % (n = 3). However, RP-HPLC data suggested (99m)Tc transchelation from LyeTx I-K-HYNIC to the co-ligands (tricine and EDDA). The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.

Incremental value of 99mTc-HYNIC-TOC SPECT/CT over whole-body planar scintigraphy and SPECT in patients with neuroendocrine tumours.

PubMed

Trogrlic, Mate; Težak, Stanko

2017-06-12

The aim of this study was to evaluate the additional value of 99m Tc-HYNIC-TOC SPECT/CT over planar whole-body (WB) scintigraphy and SPECT alone in the detection and accurate localisation of neuroendocrine tumour (NET) lesions. This study included 65 patients with a definitive histological diagnosis of NET prior to scintigraphy. Planar WB scintigraphy, SPECT, and SPECT/CT images were acquired at 4 h post-administration of 670 MBq 99m Tc-HYNIC-TOC. Additional SPECT images at 10 min after tracer administration were also acquired. Clinical and imaging follow-up findings were considered as the reference standards (minimum follow-up period, 15 months). Patient and lesion-based analyses of the efficacies of the imaging modalities were performed. While 38 patients exhibited metastasis of NETs, 27 presented no evidence of metastasis. Upon patient-based analysis, the sensitivity and specificity of SPECT/CT were found to be 88.9 and 79.3 %, respectively. The diagnostic accuracies of WB scintigraphy, 4h-SPECT, and SPECT/CT were 72.3, 73.8, and 84.6 %, respectively. The area under curve (AUC) value for SPECT/CT (0.84) was the highest, followed by those for 4h-SPECT (0.75) and WB scintigraphy (0.74). The accuracy and AUC values of SPECT/CT were significantly better compared to those of WB scintigraphy (p < 0.001), 10 min-SPECT (p < 0.001), and 4 h-SPECT (p = 0.001). The findings of SPECT/CT led to the change in treatment plan of 11 patients (16.9 %). The sensitivity and diagnostic accuracy of SPECT/CT in the evaluation of NET lesions outperforms planar WB imaging or SPECT alone.

A Rare Case of Retroperitoneal Follicular Dendritic Cell Sarcoma Identified by 99mTc-HYNIC-TOC SPECT/CT.

PubMed

Li, Yi; Xu, Xiaoping; Xu, Junyan; Huang, Dan

2018-05-31

Follicular dendritic cell sarcoma is a very rare neoplasm, which is not lymphoma, but originates from a type of immune cells called follicular dendritic cells. We presented a 37-year-old woman who has suffered from obstructive jaundice, weight loss and right upper abdominal pain for 2 months. The contrast CT revealed masses located in the region of pancreatic head and lots of enlarged retroperitoneal lymph nodes, both of which were enhanced on the artery phase of CT images. Meanwhile, Tc-HYNIC-TOC SPECT/CT revealed high activity in the corresponding lesions. After biopsy, the masses were pathologically confirmed as retroperitoneal follicular dendritic cell sarcoma.

(99m)Tc-bioorthogonal click chemistry reagent for in vivo pretargeted imaging.

PubMed

García, María Fernanda; Zhang, Xiuli; Shah, Manankumar; Newton-Northup, Jessica; Cabral, Pablo; Cerecetto, Hugo; Quinn, Thomas

2016-03-15

Metal-free click chemistry has become an important tool for pretargeted approaches in the molecular imaging field. The application of bioorthogonal click chemistry between a pretargeted trans-cyclooctene (TCO) derivatized monoclonal antibody (mAb) and a (99m)Tc-modified 1,2,4,5-tetrazine for tumor imaging was examined in vitro and in vivo. The HYNIC tetrazine compound was synthesized and structurally characterized, confirming its identity. Radiolabeling studies demonstrated that the HYNIC tetrazine was labeled with (99m)Tc at an efficiency of >95% and was radiochemically stable. (99m)Tc-HYNIC tetrazine reacted with the TCO-CC49 mAb in vitro demonstrating its selective reactivity. In vivo biodistribution studies revealed non-specific liver and GI uptake due to the hydrophobic property of the compound, however pretargeted SPECT imaging studies demonstrated tumor visualization confirming the success of the cycloaddition reaction in vivo. These results demonstrated the potential of (99m)Tc-HYNIC-tetrazine for tumor imaging with pretargeted mAbs. Copyright © 2016 Elsevier Ltd. All rights reserved.

(99m)Tc-labeled SWL specific peptide for targeting EphA2 receptor.

PubMed

Liu, Yu; Lan, Xiaoli; Wu, Tao; Lang, Juntao; Jin, Xueyan; Sun, Xun; Wen, Qiong; An, Rui

2014-07-01

EphA2, one member of the Eph receptor family, is widely expressed in multiple aggressive cancers. SWL, a small peptide identified by phage display, has high binding affinity to EphA2, suggesting that it could be exploited for targeted molecular imaging. Therefore, a novel peptide-based probe, (99m)Tc-HYNIC-SWL, was developed and its potential to specifically target EphA2-positive tumors was investigated. The SWL peptide was labeled with hydrazinonicotinic acid (HYNIC), followed by (99m)Tc labeling. Immunofluorescence staining was carried out to detect the expression of EphA2 in A549 lung cancer cells and OCM-1 melanoma cells. Saturation binding experiments were performed by incubating A549 cells with increasing concentrations of radiolabeled peptide in vitro. To test the probe in vivo, nude mice bearing either A549 or OCM-1 derived tumors were established, injected with (99m)Tc-HYNIC-SWL, and subjected to SPECT imaging. Mice injected with excess unlabeled SWL were used as a specific control. Ex vivo γ-counting of dissected tissues from the mice was also performed to evaluate biodistribution. Immunofluorescence staining showed that A549 cells intensively expressed EphA2, while OCM-1 cells had little expression. (99m)Tc-HYNIC-SWL displayed high binding affinity with A549 cells (KD=2.6±0.7nM). From the SPECT images and the results of the biodistribution study, significantly higher uptake of the tracer was seen in A549 tumors (1.44±0.12 %ID/g) than in OCM-1 tumors (0.43±0.20 %ID/g) at 1h after injection. Pre-injection with excess unlabeled peptide in A549-bearing nude mice, significantly reduced tumor uptake of the radiolabeled probe (0.58±0.20 %ID/g) was seen. These data suggest that (99m)Tc-HYNIC-SWL specifically targets EphA2 in tumors. The expression of EphA2 can be noninvasively investigated using (99m)Tc-HYNIC-SWL by SPECT imaging. The in vitro and in vivo characteristics of (99m)Tc-HYNIC-SWL make it a promising probe for EphA2-positive tumor imaging

La preparacion en ciencia de los candidatos a maestros del nivel elemental primario segun la reforma de la educacion cientifica en Puerto Rico: Una propuesta de secuencia curricular

NASA Astrophysics Data System (ADS)

Rodriguez Plaza, Evelyn

El proposito de esta investigacion fue identificar los componentes de la preparacion en ciencia que deben recibir los estudiantes del Bachillerato en Artes en Educacion Elemental, Nivel Primario, de acuerdo a los documentos que dirigen la reforma de la educacion cientifica en Puerto Rico. Tambien, se identificaron los componentes de los cursos que forman parte de la preparacion en ciencia de estos estudiantes. Se compararon los componentes de la preparacion en ciencia y los componentes de los cursos para determinar congruencias y discrepancias. Con los datos recopilados se identificaron los componentes de los cursos de una secuencia curricular para la preparacion en ciencia de los candidatos a maestros del nivel elemental primario. La secuencia curricular que se propone en esta investigacion incluye cursos de contenido cientifico y de metodologia en la ensenanza de la ciencia disenados para satisfacer las necesidades de los candidatos. Se recomienda que en los procesos para el diseno, la implantacion y la evaluacion de estos cursos participen profesores de ciencia, profesores de educacion y maestros del nivel elemental primario. Todos los cursos de la secuencia curricular deben tener un enfoque constructivista. Las experiencias educativas que se incluyan en los cursos deben aspirar a desarrollar en los candidatos los atributos de la cultura cientifica y actitudes positivas hacia la ciencia y hacia la ensenanza de esta disciplina. El modelaje por parte de los profesores que ensenen los cursos de la secuencia curricular es fundamental en el desarrollo profesional de los candidatos. Se recomienda que en los cursos de contenido cientifico se estudien los conceptos y los conocimientos cientificos que forman parte del curriculo de Kindergarten a tercer grado de forma integrada y con una profundidad universitaria. Estos cursos deben tener un enfoque interdisciplinario e incluir el estudio de la naturaleza de la ciencia y un componente de laboratorio para desarrollar los

Oxidation of methionine - is it limiting the diagnostic properties of 99mTc-labeled Exendin-4, a Glucagon-Like Peptide-1 receptor agonist?

PubMed

Janota, Barbara; Karczmarczyk, Urszula; Laszuk, Ewa; Garnuszek, Piotr; Mikołajczak, Renata

2016-01-01

Preliminary clinical evaluation of 99mTc-EDDA/HYNIC-Met14-Exendin-4 showed that the complex offers new diagnostic possibilities for insulinoma and MTC. Exendin-4 contains methionine at position 14 in the amino acid chain, which may be oxidized to methionine sulfoxide and, from the pharmaceutical point of view, the oxidized moiety becomes an undesired impurity in the final radioactive preparation. Therefore, the aim of this study was to investigate the influence of commonly used methods to eliminate the effect of methionine oxidation in peptides, i.e. the replacement of methionine by norleucine (Nle) and the addition of L-methionine, on the in vitro stability and the biodistribution. 99mTc-EDDA/HYNIC-Met14-Exendin-4, 99mTc-EDDA/HYNIC-Nle14-Exendin-4, 99mTc-EDDA/HYNIC-Met14-Ex-endin-4 with the addition of L-methionine and an oxidized form of Exendin-4, i.e. 99mTc-EDDA/HYNIC-Met14(ox)-Exendin-4 were compared in vivo with 68Ga-NODAGA-Nle14-Exendin-4 in normal Wistar rats. The stability and lipophilicity were determined in vitro. Biodistribution studies confirmed the specific uptake of all tested complexes in the GLP-1 positive organs: lungs, pancreas and stomach. The uptake of 99mTc-EDDA/HYNIC-Met14-Exendin-4 with the addition of L-methionine and for 68Ga-NODAGA-Nle14-Exendin-4 at 1h p.i. was around 2-fold higher than that of 99mTc-EDDA/HYNIC-Met14-Exendin-4 and 99mTc-EDDA/HYNIC-Nle14-Exendin-4. Although the substitution of methionine by norleucine in the HYNIC-Exendin-4 did not result in improved bio-distribution, the use of L-methionine, as the excipient that inhibits the oxidation of methionine in the peptide chain resulted in higher lung/blood and stomach/blood uptake ratios. Our results confirmed that methionine at position 14 of amino acid chain of Exendin-4 plays an important role in the interaction with GLP-1 receptor positive tissue.

Somatostatin Receptor SPECT/CT using 99mTc Labeled HYNIC-TOC Aids in Diagnosis of Primary Optic Nerve Sheath Meningioma.

PubMed

Chandra, Piyush; Purandare, Nilendu; Shah, Sneha; Agrawal, Archi; Rangarajan, Venkatesh

2017-01-01

Primary optic nerve sheath meningiomas (ONSM) are rare, benign and slow growing tumor involving the intra-orbital/intra-canalicular segment of the optic nerve. Untreated, they can potentially lead to visual deterioration. Magnetic resonance (MR) is the gold standard imaging modality for diagnosing the entity. Often, a clinical dilemma exists to narrow the differential diagnosis of an enhancing intra-orbital mass on MR. Molecular imaging provides a high degree of precision in diagnosing meningioma in view of relatively high levels of somatostatin receptor expression by these tumors. The following case demonstrates the potential clinical utility of somatostatin receptor SPECT using 99m Tc- labeled HYNIC-TOC in clinical diagnosis of ONSM.

Tc-labeling of Peptidomimetic Antagonist to Selectively Target alpha(v)beta(3) Receptor-Positive Tumor: Comparison of PDA and EDDA as co-Ligands.

PubMed

Shin, In Soo; Maeng, Jin Soo; Jang, Beom-Su; You, Eric; Cheng, Kenneth; Li, King C P; Wood, Bradford; Carrasquillo, Jorge A; Danthi, S Narasimhan; Paik, Chang H

2010-01-01

OBJECTIVES: The aim of this research was to synthesize radiolabeled peptidomimetic integrin alpha(v)beta(3) antagonist with (99m)Tc for rapid targeting of integrin alpha(v)beta(3) receptors in tumor to produce a high tumor to background ratio. METHODS: The amino terminus of 4-[2-(3,4,5,6-tetra-hydropyrimidin-2-ylamino)-ethyloxy]benzoyl-2-(S)-[N-(3-amino-neopenta-1-carbamyl)]-aminoethylsulfonyl-amino-beta-alanine hydrochloride (IAC) was conjugated with N-hydroxysuccinimide ester of HYNIC and labeled with (99m)Tc using tricine with either 1,5-pyridinedicarboxylic acid (PDA) or ethylenediamine-N,N'-diacetic acid (EDDA) as the co-ligand. The products, (99m)Tc EDDA(2)/HYNIC-IAC (P1) and (99m)Tc PDA (tricin)/HYNIC-IAC (P2) were subjected to in vitro serum stability, receptor-binding, biodistribution and imaging studies. RESULTS: P1 and P2 were synthesized with an overall yield of >80%. P1 was slightly more stable than P2 when incubated in serum at 37 degrees C for 18 hrs (84 vs 77% intact). The In vitro receptor-binding of P1 was higher than that of P2 (78.02 +/- 13.48 vs 51.05 +/- 14.05%) when incubated with alpha(v)beta(3) at a molar excess (0.8 muM). This receptor binding was completely blocked by a molar excess of an unlabeled peptidomimetic antagonist. Their differences shown in serum stability and the receptor-binding appeared to be related to their biological behaviors in tumor uptake and retention; the 1 h tumor uptakes of P1 and P2 were 3.17+/-0.52 and 2.13+/-0.17 % ID/g, respectively. P1 was retained in the tumor longer than P2. P1 was excreted primarily through the renal system whereas P2 complex was excreted equally via both renal and hepatobiliary systems. Thus, P1 was retained in the whole-body with 27.25 +/- 3.67% ID at 4 h whereas 54.04 +/- 3.57% ID of P2 remained in the whole-body at 4 h. This higher whole-body retention of P2 appeared to be resulted from a higher amount of radioactivity retained in liver and intestine. These findings were supported by

99mTc-labeled PSMA inhibitor: Biokinetics and radiation dosimetry in healthy subjects and imaging of prostate cancer tumors in patients.

PubMed

Santos-Cuevas, Clara; Davanzo, Jenny; Ferro-Flores, Guillermina; García-Pérez, Francisco O; Ocampo-García, Blanca; Ignacio-Alvarez, Eleazar; Gómez-Argumosa, Edgar; Pedraza-López, Martha

2017-09-01

The prostate-specific membrane antigen (PSMA) is expressed in epithelial cells of the prostate and highly overexpressed in 95% of advanced prostate cancers. The aims of this study was to estimate the biokinetics and dosimetry of 99m Tc-EDDA/HYNIC-iPSMA ( 99m Tc-labeled PSMA inhibitor) in eight healthy subjects and evaluate its usefulness as a tumor-imaging agent in eight prostate cancer patients. 99m Tc-EDDA/HYNIC-iPSMA was obtained from a lyophilized formulation with radiochemical purities >98%, determined by reversed-phase HPLC and ITLC-SG analyses. Whole-body images from eight healthy subjects were acquired at 20min, and at 2, 6 and 24h after 99m Tc-EDDA/HYNIC-iPSMA administration. Regions of interest (ROIs) were drawn around the source organs on each time frame. Each ROI was corrected by background, attenuation, scattered radiation and physical decay. The image sequence was used to extrapolate the 99m Tc-EDDA/HYNIC-iPSMA time-activity curves of each organ to adjust the biokinetic model and calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation doses. In eight prostate cancer patients with histologically confirmed cancer, whole-body SPECT/CT images were obtained at 3h. The blood activity showed a half-life value of 4.98min for the fast component (T 1/2 α=ln2/8.34), 2.49h for the first slow component (T 1/2 β=ln2/0.278), and 9.24h for the second slow component (T 1/2 γ=ln2/0.076). Images from patients showed an average tumor/background ratio of 8.99±3.27 at 3h. The average equivalent doses calculated for a study using 740MBq were 3.80, 7.06, 9.69, 10.70, and 28.80mSv for the breast, spleen, salivary glands, liver, and kidneys respectively, with an effective dose of 3.42±0.78mSv. All the absorbed doses were comparable to those known for most of the 99m Tc studies. 99m Tc-EDDA/HYNIC-iPSMA obtained from kit formulations showed high tumor uptake in

Evaluation of New Tc-99m-Labeled Arg-X-Asp-Conjugated Alpha-Melanocyte Stimulating Hormone Peptides for Melanoma Imaging

PubMed Central

Flook, Adam M.; Yang, Jianquan; Miao, Yubin

2013-01-01

The purpose of this study was to examine the melanoma targeting and imaging properties of two new 99mTc-labeled Arg-X-Asp-conjugated alpha-melanocyte stimulating hormone (α-MSH) peptides. RTD-Lys-(Arg11)CCMSH {c[Asp-Arg-Thr-Asp-DTyr]-Lys-Cys-Cys-Glu-His-DPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2} and RVD-Lys-(Arg11)CCMSH peptides were synthesized and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution and melanoma imaging properties of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The IC50 values of RTD-Lys-(Arg11)CCMSH and RVD-Lys-(Arg11)CCMSH were 0.7 ± 0.07 and 1.0 ± 0.3 nM in B16/F1 melanoma cells. Both 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH displayed high melanoma uptake. 99mTc-RTD-Lys-(Arg11)CCMSH exhibited the peak tumor uptake of 18.77 ± 5.13% ID/g at 2 h post-injection, whereas 99mTc-RVD-Lys-(Arg11)CCMSH reached the peak tumor uptake of 19.63 ± 4.68% ID/g at 4 h post-injection. Both 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH showed low accumulation in normal organs (<1.7% ID/g) except for the kidneys at 2 h post-injection. The renal uptake of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH was 135.14 ± 23.62 and 94.01 ± 18.31% ID/g at 2 h post-injection, respectively. The melanoma lesions were clearly visualized by SPECT/CT using either 99mTc-RTD-Lys-(Arg11)CCMSH or 99mTc-RVD-Lys-(Arg11)CCMSH as an imaging probe at 2 h post-injection. Overall, the introduction of Thr or Val residue retained high melanoma uptake of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH. However, high renal uptake of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH need to be reduced to facilitate their future applications. PMID:23885640

Evaluation of new Tc-99m-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone peptides for melanoma imaging.

PubMed

Flook, Adam M; Yang, Jianquan; Miao, Yubin

2013-09-03

The purpose of this study was to examine the melanoma targeting and imaging properties of two new (99m)Tc-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RTD-Lys-(Arg(11))CCMSH {c[Asp-Arg-Thr-Asp-DTyr]-Lys-Cys-Cys-Glu-His-DPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2} and RVD-Lys-(Arg(11))CCMSH peptides were synthesized, and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution and melanoma imaging properties of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The IC50 values of RTD-Lys-(Arg(11))CCMSH and RVD-Lys-(Arg(11))CCMSH were 0.7 ± 0.07 and 1.0 ± 0.3 nM in B16/F1 melanoma cells. Both (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH displayed high melanoma uptake. (99m)Tc-RTD-Lys-(Arg(11))CCMSH exhibited the highest tumor uptake of 18.77 ± 5.13% ID/g at 2 h postinjection, whereas (99m)Tc-RVD-Lys-(Arg(11))CCMSH reached the highest tumor uptake of 19.63 ± 4.68% ID/g at 4 h postinjection. Both (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH showed low accumulation in normal organs (<1.7% ID/g) except for the kidneys at 2 h postinjection. The renal uptake of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH was 135.14 ± 23.62 and 94.01 ± 18.31% ID/g at 2 h postinjection, respectively. The melanoma lesions were clearly visualized by single-photon emission computed tomography (SPECT)/CT using either (99m)Tc-RTD-Lys-(Arg(11))CCMSH or (99m)Tc-RVD-Lys-(Arg(11))CCMSH as an imaging probe at 2 h postinjection. Overall, the introduction of Thr or Val residue retained high melanoma uptake of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH. However, high renal uptake of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH need to be reduced to facilitate their future applications.

Evaluation of a 99mTc-labeled AnnexinA5 variant for non-invasive SPECT imaging of cell death in liver, spleen and prostate.

PubMed

Greupink, Rick; Sio, Charles F; Ederveen, Antwan; Orsel, Joke

2009-12-01

We investigate radio-labeling and pharmacokinetics of a new AnnexinA5 variant (HYNIC-cys-AnxA5) and then assess its utility for the non-invasive detection of cell death in liver, spleen and prostate. AnnexinA5 binds to phosphatidylserine expressed on the surface of apoptotic and necrotic cells. Contrary to other AnnexinA5 variants, the new cys-AnxA5 allows for site-specific conjugation of a hydrazinonicotinamide-maleimide moiety and subsequent radio-labeling with (99m)Tc at a position not involved in the AnxA5-phosphatidylserine interaction. Distribution of (99m)Tc-HYNIC-cys-AnxA5 was studied in rats, both invasively and via SPECT/CT. Cycloheximide was used to induce cell death in liver and spleen, whereas apoptosis in the prostate was induced by castration. HYNIC-cys-AnxA5 was efficiently and reproducibly labeled with (99m)Tc. Blood clearance of radioactivity after iv-injection was adequately described by a two-compartment model, the renal cortex representing the main site of accumulation. Cycloheximide treatment resulted in increased accumulation of intravenous-injected (99m)Tc-HYNIC-cys-AnxA5 in liver and spleen over controls, which correlated well with TUNEL staining for cell death in corresponding tissue sections. However, the increase in TUNEL-positive prostate epithelial cells observed following castration was not paralleled by greater (99m)Tc-HYNIC-cys-AnxA5 accumulation. (99m)Tc-HYNIC-cys-AnxA5 appears a suitable tracer for assessment of cell death in liver and spleen, but not prostate.

An intrapatient comparison of 99mTc-EDDA/HYNIC-TOC with 111In-DTPA-octreotide for diagnosis of somatostatin receptor-expressing tumors.

PubMed

Gabriel, Michael; Decristoforo, Clemens; Donnemiller, Eveline; Ulmer, Hanno; Watfah Rychlinski, Christine; Mather, Stephen J; Moncayo, Roy

2003-05-01

The aim of this study was to compare the imaging abilities of the recently developed somatostatin analog, (99m)Tc-hydrazinonicotinyl-Tyr(3)-octreotide ((99m)Tc-HYNIC-TOC [(99m)Tc-TOC]), with (111)In-diethylenediaminepentaacetic acid-D-Phe(1)-octreotide ((111)In-OCT [Octreoscan]) in patients undergoing routine somatostatin receptor (SSTR) scintigraphy. Forty-one patients (20 men, 21 women; age range, 29-75 y; mean age, 56.7 y) with either histologically proven or biologically and clinically suspected endocrine tumors were enrolled in the study. Four groups were distinguished: (a) patients being evaluated for the detection and localization of neuroendocrine tumors (n = 6), (b) tumor staging (n = 19), (c) patients being investigated to determine the SSTR status of tumor lesions (n = 11), and (d) patient follow-up studies (n = 5). Each patient received a mean activity of 150 MBq (111)In-OCT and 350-400 MBq (99m)Tc-TOC. Scintigraphy with (99m)Tc-TOC was performed 4 h after injection and scintigraphy with (111)In-OCT was performed 4 and 24 h after injection. SPECT studies of areas of interest were performed 4 h after injection for both tracers as well as at 24 h after injection for (111)In-OCT. The time interval between the studies using each tracer ranged from 2 to 22 d (mean interval, 9.3 d). (111)In-OCT and (99m)Tc-TOC showed an equivalent scan result in 32 patients (78%), 9 cases showed discrepancies (22%), false-negative results with (111)In-OCT were seen in 6 cases (14.6%), whereas (99m)Tc-TOC was false-positive in 2 cases (4.9%). (111)In-OCT was true-negative in both cases. The false-positive findings of the (99m)Tc-TOC studies were caused by nonspecific uptake in the bowel. In 1 case, (99m)Tc-TOC correctly identified a metastasis in the lumbar spine but both scan results were false-positive because of an inflammatory process. In 21 patients with SSTR-expressing tumors, the semiquantitative region-of-interest analysis showed that (99m)Tc-TOC achieved higher tumor

99mTc-labeling of Peptidomimetic Antagonist to Selectively Target αvβ3 Receptor-Positive Tumor: Comparison of PDA and EDDA as co-Ligands

PubMed Central

Shin, In Soo; Maeng, Jin Soo; Jang, Beom-Su; You, Eric; Cheng, Kenneth; Li, King C.P; Wood, Bradford; Carrasquillo, Jorge A.; Danthi, S. Narasimhan; Paik, Chang H.

2010-01-01

Objectives The aim of this research was to synthesize radiolabeled peptidomimetic integrin αvβ3 antagonist with 99mTc for rapid targeting of integrin αvβ3 receptors in tumor to produce a high tumor to background ratio. Methods The amino terminus of 4-[2-(3,4,5,6-tetra-hydropyrimidin-2-ylamino)-ethyloxy]benzoyl-2-(S)-[N-(3-amino-neopenta-1-carbamyl)]-aminoethylsulfonyl-amino-β-alanine hydrochloride (IAC) was conjugated with N-hydroxysuccinimide ester of HYNIC and labeled with 99mTc using tricine with either 1,5-pyridinedicarboxylic acid (PDA) or ethylenediamine-N,N′-diacetic acid (EDDA) as the co-ligand. The products, 99mTc EDDA2/HYNIC-IAC (P1) and 99mTc PDA (tricin)/HYNIC-IAC (P2) were subjected to in vitro serum stability, receptor-binding, biodistribution and imaging studies. Results P1 and P2 were synthesized with an overall yield of >80%. P1 was slightly more stable than P2 when incubated in serum at 37 °C for 18 hrs (84 vs 77% intact). The In vitro receptor-binding of P1 was higher than that of P2 (78.02 ± 13.48 vs 51.05 ± 14.05%) when incubated with αvβ3 at a molar excess (0.8 μM). This receptor binding was completely blocked by a molar excess of an unlabeled peptidomimetic antagonist. Their differences shown in serum stability and the receptor-binding appeared to be related to their biological behaviors in tumor uptake and retention; the 1 h tumor uptakes of P1 and P2 were 3.17±0.52 and 2.13±0.17 % ID/g, respectively. P1 was retained in the tumor longer than P2. P1 was excreted primarily through the renal system whereas P2 complex was excreted equally via both renal and hepatobiliary systems. Thus, P1 was retained in the whole-body with 27.25 ± 3.67% ID at 4 h whereas 54.04 ± 3.57% ID of P2 remained in the whole-body at 4 h. This higher whole-body retention of P2 appeared to be resulted from a higher amount of radioactivity retained in liver and intestine. These findings were supported by imaging studies showing higher tumor

A (99m) Tc-tricine-HYNIC-labeled peptide targeting the neurotensin receptor for single-photon imaging in malignant tumors.

PubMed

Erfani, Mostafa; Zarrabi Ahrabi, Nakisa; Shafiei, Mohammad; Shirmardi, Seyed Pezhman

2014-03-01

In this study, a new neurotensin (NT) analog was labeled with (99m) Tc via HYNIC chelator and tricine as coligand and investigated further. An NT (7-13) analog was prepared, and labeling with (99m) Tc was performed. The internalization rate and biodistribution of radiopeptide were studied in HT-29 cells and nude mice bearing tumor, respectively. Radiolabeling with (99m) Tc was performed at high specific activities (54 MBq/nmol) with an acceptable labeling yield (>95%). In vitro cell line studies showed a specific internalization uptake up to 13.23 ± 0.45% during 4 h which was blocked in the presence of excess cold peptide to 0.83 ± 0.15%. In biodistribution studies, uptake was observed in NT receptor-positive organs so that after 1 h the uptakes in mouse intestine and tumor were 1.23 ± 0.16% ID/g and 1.12 ± 0.11% ID/g, respectively. In animals co-injected with excess cold peptide, reduction uptake in tumor and intestines were 73% (1.10% vs. 0.29% ID/g at 4 h) and 61% (1.22% vs. 0.47% ID/g at 4 h) respectively. Predominant renal excretion pathway with a highest accumulation of activity in bladder was observed for this radiopeptide. This radiolabeled peptide could be a candidate for detection of NT positive tumors. Copyright © 2014 John Wiley & Sons, Ltd.

Synthesis and evaluation of a 99mTc-labeled tubulin-binding agent for tumor imaging.

PubMed

Erfani, Mostafa; Shamsaei, Mojtaba; Mohammadbaghery, Faiyaz; Shirmardi, Seyed Pezhman

2014-05-30

Cholchicine and its derivatives are very potent tubulin-binding compounds and can be used as a potential tumor targeting agents. In this study, colchicine was labeled with (99m) Tc via hydrazinonicotinic acid (HYNIC) and was investigated further. HYNIC/cholchicine was synthesized and labeling with (99m)Tc was performed at 95 °C for 15 min and radiochemical analysis included HPLC method. The stability of radiconjugate was checked in the presence of human serum at 37 °C up to 24 h. Biodistribution was studied in breast tumor-bearing mice. Labeling yield of 95.8 ± 0.54% was obtained corresponding to a specific activity of 54 MBq/µmol. Radioconjugate showed good stability in the presence of human serum. Biodistribution studies in tumor-bearing mice showed that (99m) Tc/HYNIC/colchicine conjugate accumulated in tumor with good uptake (3.17 ± 0.14% g/g at 1 h post-injection). The radioconjugate was cleared fast from normal organs and showed clearance through urinary and hepatobiliary systems with accumulation of activity in kidneys and intestine. This radioconjugate may be useful to assess the presence of tumor by imaging. Copyright © 2014 John Wiley & Sons, Ltd.

Substitution of the Lys Linker with the β-Ala Linker Dramatically Decreased the Renal Uptake of 99mTc-Labeled Arg-X-Asp-Conjugated and X-Ala-Asp-Conjugated α-Melanocyte Stimulating Hormone Peptides

PubMed Central

2015-01-01

The purpose of this study was to examine whether the substitution of the Lys linker with the β-Ala could reduce the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-β-Ala-(Arg11)CCMSH (1) {c[Arg-Ser-Asp-dTyr-Asp]-β-Ala-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RTD-β-Ala-(Arg11)CCMSH (2), RVD-β-Ala-(Arg11)CCMSH (3), RAD-β-Ala-(Arg11)CCMSH (4), NAD-β-Ala-(Arg11)CCMSH (5), and EAD-β-Ala-(Arg11)CCMSH (6) peptides were synthesized and evaluated for their melanocortin 1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of their 99mTc-conjugates were determined in B16/F1 melanoma-bearing C57 mice. The substitution of the Lys linker with β-Ala linker dramatically reduced the renal uptake of all six 99mTc-peptides. 99mTc-4 exhibited the highest melanoma uptake (15.66 ± 6.19% ID/g) and the lowest kidney uptake (20.18 ± 3.86% ID/g) among these 99mTc-peptides at 2 h postinjection. The B16/F1 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using 99mTc-4 as an imaging probe. PMID:25290883

Substitution of the Lys linker with the β-Ala linker dramatically decreased the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone peptides.

PubMed

Flook, Adam M; Yang, Jianquan; Miao, Yubin

2014-11-13

The purpose of this study was to examine whether the substitution of the Lys linker with the β-Ala could reduce the renal uptake of (99m)Tc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-β-Ala-(Arg(11))CCMSH (1) {c[Arg-Ser-Asp-dTyr-Asp]-β-Ala-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RTD-β-Ala-(Arg(11))CCMSH (2), RVD-β-Ala-(Arg(11))CCMSH (3), RAD-β-Ala-(Arg(11))CCMSH (4), NAD-β-Ala-(Arg(11))CCMSH (5), and EAD-β-Ala-(Arg(11))CCMSH (6) peptides were synthesized and evaluated for their melanocortin 1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of their (99m)Tc-conjugates were determined in B16/F1 melanoma-bearing C57 mice. The substitution of the Lys linker with β-Ala linker dramatically reduced the renal uptake of all six (99m)Tc-peptides. (99m)Tc-4 exhibited the highest melanoma uptake (15.66 ± 6.19% ID/g) and the lowest kidney uptake (20.18 ± 3.86% ID/g) among these (99m)Tc-peptides at 2 h postinjection. The B16/F1 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using (99m)Tc-4 as an imaging probe.

99mTc-EDDA/HYNIC-TOC and (18)F-FDG in thyroid cancer patients with negative (131)I whole-body scans.

PubMed

Gabriel, Michael; Froehlich, Franz; Decristoforo, Clemens; Ensinger, Christian; Donnemiller, Eveline; von Guggenberg, Elisabeth; Heute, Dirk; Moncayo, Roy

2004-03-01

Several studies have reported on the expression of somatostatin receptors in patients with differentiated thyroid cancer (DTC). The aim of this study was to evaluate the imaging abilities of a recently developed technetium-99m labelled somatostatin analogue, (99m)Tc-EDDA/HYNIC-TOC ((99m)Tc-TOC), in terms of precise localisation of disease. The study population comprised 54 patients (24 men, 30 women; age range 22-90 years) with histologically confirmed DTC who presented with recurrent or persistent disease as indicated by elevated Tg levels after initial treatment. All patients were negative on the iodine-131 post-therapy whole-body scans. Fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) was performed in a subgroup of 36 patients. The study population consisted of two groups: Group A ( n=22) comprised patients with disease recurrence as shown by elevated Tg levels but without detectable pathology. In group B ( n=32), pre-existing lesions were known. Among the 54 cases, SSTR scintigraphy was true positive in 33 (61.1%), true negative in 4 (7.4%) and false negative in 17 (31.5%) cases, which resulted in a sensitivity of 66%. A total of 138 tumour foci were localised in 33 patients. The fraction of true positive (99m)Tc-TOC findings was positively correlated ( P<0.01) with elevated Tg levels (higher than 30 ng/ml). Despite two false positive findings, analysis on a lesion basis demonstrated better diagnostic efficacy with (18)F-FDG PET ( P<0.001); however, it also revealed substantial agreement between the imaging techniques [Cohen's kappa of 0.62 (0.47-0.78)]. In conclusion, scintigraphy with (99m)Tc-TOC might be a promising tool for treatment planning; it is easy to perform and showed sufficient accuracy for localisation diagnostics in thyroid cancer patients with recurrent or metastatic disease.

Clinical application of SPECT-CT with 99mTc-Tektrotyd in bronchial and thymic neuroendocrine tumors (NETs).

PubMed

Sergieva, Sonya; Robev, Bozhil; Dimcheva, Milena; Fakirova, Albena; Hristoskova, Radka

2016-01-01

Neuroendocrine tumors (NETs) of the thorax including bronchial and thymic tumors belong to foregut NETs. Limited loco-regional thoracic NETs can be resected with surgery, but in extensive metastatic disease the treatment is mainly palliative. A high incidence and density of somatostatin receptors (SSTR2, SSTR3, and SSTR5) are found in thoracic NETs. The purpose of this study was to evaluate the role of SPECT-CT somatostatin receptor scintigraphy (SRS) with 99mTc-Tektrotyd for imaging, staging and follow up of patients with bronchial and thymic neuroendocrine tumors. Forty-one patients with thoracic tumors with neuroendocrine differentiation were studied. Sixty-eight examinations including SPECT-CT studies of the neck and chest and/or abdomen and pelvis were carried out 2-4 hrs. post i.v. administration of aver-age 740 MBq activity dose of 99mTc-EDDA/HYNIC-TOC (Tektrotyd, Polatom). In all 41 investigated patients we obtained 81.25% (13/16), 88% (22/25) and 85.36% (35/41) of sensitivity, specificity and accuracy of this diagnostic approach, respectively. Somatostatin-receptor scintigraphy correctly identified all primary NETs located in the lungs and thymus. SPECT-CT studies with 99mTc-EDDA/HYNIC-TOC resulted in exact pre-surgical and pre-treatment N/M staging of bronchial and thymic NETs, except 2 cases with multiple hepatic metastases and 1 with massive suprarenal metastasis. It can be concluded that SPECT-CT with 99mTc-EDDA/HYNIC-TOC is a valuable tool for staging and follow-up of patients with thoracic NETs.

99mTc Labeled Glucagon-Like Peptide-1-Analogue (99mTc-GLP1) Scintigraphy in the Management of Patients with Occult Insulinoma

PubMed Central

Sowa-Staszczak, Anna; Trofimiuk-Müldner, Małgorzata; Stefańska, Agnieszka; Tomaszuk, Monika; Buziak-Bereza, Monika; Gilis-Januszewska, Aleksandra; Jabrocka-Hybel, Agata; Głowa, Bogusław; Małecki, Maciej; Bednarczuk, Tomasz; Kamiński, Grzegorz; Kowalska, Aldona; Mikołajczak, Renata; Janota, Barbara; Hubalewska-Dydejczyk, Alicja

2016-01-01

Introduction The aim of this study was to assess the utility of [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 scintigraphy in the management of patients with hypoglycemia, particularly in the detection of occult insulinoma. Materials and Methods Forty patients with hypoglycemia and increased/confusing results of serum insulin and C-peptide concentration and negative/inconclusive results of other imaging examinations were enrolled in the study. In all patients GLP-1 receptor imaging was performed to localise potential pancreatic lesions. Results Positive results of GLP-1 scintigraphy were observed in 28 patients. In 18 patients postsurgical histopathological examination confirmed diagnosis of insulinoma. Two patients had contraindications to the surgery, one patient did not want to be operated. One patient, who presented with postprandial hypoglycemia, with positive result of GLP-1 imaging was not qualified for surgery and is in the observational group. Eight patients were lost for follow up, among them 6 patients with positive GLP-1 scintigraphy result. One patient with negative scintigraphy was diagnosed with malignant insulinoma. In two patients with negative scintigraphy Munchausen syndrome was diagnosed (patients were taking insulin). Other seven patients with negative results of 99mTcGLP-1 scintigraphy and postprandial hypoglycemia with C-peptide and insulin levels within the limits of normal ranges are in the observational group. We would like to mention that 99mTc-GLP1-SPECT/CT was also performed in 3 pts with nesidioblastosis (revealing diffuse tracer uptake in two and a focal lesion in one case) and in two patients with malignant insulinoma (with the a focal uptake in the localization of a removed pancreatic headin one case and negative GLP-1 1 scintigraphy in the other patient). Conclusions 99mTc-GLP1-SPECT/CT could be helpful examination in the management of patients with hypoglycemia enabling proper localization of the pancreatic lesion and effective

Comparison of Biological Properties of 99mTc-Labeled Cyclic RGD Peptide Trimer and Dimer Useful as SPECT Radiotracers for Tumor Imaging

PubMed Central

Zhao, Zuo-Quan; Yang, Yong; Fang, Wei; Liu, Shuang

2016-01-01

Introduction This study sought to evaluate a 99mTc-labeled trimeric cyclic RGD peptide (99mTc-4P-RGD3) as the new radiotracer for tumor imaging. The objective was to compare its biological properties with those of 99mTc-3P-RGD2 in the same animal model. Methods HYNIC-4P-RGD3 was prepared by reacting 4P-RGD3 with excess HYNIC-OSu in the presence of diisopropylethylamine. 99mTc-4P-RGD3 was prepared using a kit formulation, and evaluated for its tumor-targeting capability and biodistribution properties in the BALB/c nude mice with U87MG human glioma xenografts. Planar and SPECT imaging studies were performed in athymic nude mice with U87MG glioma xenografts. For comparison purpose, 99mTc-3P-RGD2 (a αvβ3-targeted radiotracer currently under clinical evaluation for tumor imaging in cancer patients) was also evaluated in the same animal models. Blocking experiments were used to demonstrate the αvβ3 specificity of 99mTc-4P-RGD3. Results 99mTc-4P-RGD3 was prepared with >95% RCP and high specific activity (~200 GBq/µmol). 99mTc-4P-RGD3 and 99mTc-3P-RGD2 shared almost identical tumor uptake and similar biodistribution properties. 99mTc-4P-RGD3 had higher uptake than 99mTc-3P-RGD2 in the intestines and kidneys; but it showed better metabolic stability. The U87MG tumors were clearly visualized by SPECT with excellent contrast with 99mTc-4P-RGD3 and 99mTc-3P-RGD2. Conclusion Increasing peptide multiplicity from 3P-RGD2 to 4P-RGD3 offers no advantages with respect to the tumor-targeting capability. 99mTc-4P-RGD3 is as good a SPECT radiotracer as 99mTc-3P-RGD2 for imaging αvβ3-positive tumors. PMID:27556955

Differential diagnosis of solitary pulmonary nodules based on 99mTc-EDDA/HYNIC-TOC scintigraphy: the effect of tumour size on the optimal method of image assessment.

PubMed

Płachcińska, Anna; Mikołajczak, Renata; Kozak, Józef; Rzeszutek, Katarzyna; Kuśmierek, Jacek

2006-09-01

The aim of the study was to determine an optimal method for the evaluation of scintigrams obtained with (99m)Tc-EDDA/HYNIC-TOC for the purpose of differential diagnosis of solitary pulmonary nodules (SPNs) and to assess the diagnostic value of the method. Eighty-five patients (48 males and 37 females, mean age 57 years, range 34-78 years) were enrolled in the study. Patients underwent (99m)Tc-EDDA/HYNIC-TOC scintigraphy for the purpose of differential diagnosis of SPNs (size between 1 and 4 cm). Images of all patients were evaluated visually in a prospective manner. Positive scintigraphic results were found in 37 out of 40 (93%) patients with malignant SPNs including 34 out of 35 (97%) patients with primary lung carcinoma. Two remaining false negative cases turned out to be metastatic lesions of malignant melanoma and leiomyosarcoma. Among 45 benign tumours, negative results were obtained in 31 cases (69%) and positive results in 14. The accuracy of the method was 80%. Analysis of the results of the visual assessment of scintigrams revealed a significantly higher frequency of false positive results among larger nodules (diameter at least 1.4 cm). Uptake of the tracer in those nodules was therefore assessed semi-quantitatively (using the tumour-to-background ratio), in expectation of an improvement in the low specificity of the visual method. The semi-quantitative assessment reduced the total number of false positive results in a subgroup of larger nodules from 13 to six, while preserving the high sensitivity of the method. The combination of visual analysis (for lesions smaller than 1.4 cm in diameter) and semi-quantitative assessment (for larger lesions) provided a high sensitivity of the method and significantly improved its specificity (84%) and accuracy (88%) in comparison with visual analysis (p<0.05).

Evaluation of 99mTc-3PRGD2 integrin receptor imaging in hepatocellular carcinoma tumour-bearing mice: comparison with 18F-FDG metabolic imaging.

PubMed

Zheng, Jieling; Miao, Weibing; Huang, Chao; Lin, Haoxue

2017-07-01

Our study was designed to explore the utility of 99m Tc-HYNIC-PEG 4 -E[PEG 4 -c(RGDfK)] 2 ( 99m Tc-3PRGD 2 ) for the detection of hepatocellular carcinoma (HCC) and specifically to compare the diagnostic performance of 99m Tc-3PRGD 2 integrin receptor imaging and 2-18-fluoro-2-deoxy-D-glucose ( 18 F-FDG) metabolic imaging in a nude mouse model. 99m Tc-3PRGD 2 was synthesized using a HYNIC-3PRGD 2 lyophilized kit with 99m TcO 4 labelling. The nude mouse animal model was established by subcutaneously injecting 5 × 10 7 /ml HepG2 cells into the shoulder flank of each mouse. Biodistribution studies were performed at 0.5, 1, 2 and 4 h after intravenous administration of 0.37 MBq of 99m Tc-3PRGD 2 . Immunohistochemistry was performed to evaluate the expression level of integrin αvβ3 in the HCC tissues. Dynamic imaging was performed using list-mode after the administration of 55.5 MBq of 99m Tc-3PRGD 2 , to reconstruct the multiphase images and acquire the best initial scan time. At 8, 12, 16, 20 and 24 days after inoculation with HepG2 cells, 55.5 MBq of 99m Tc-3PRGD 2 and 37 MBq of 18 F-FDG were injected successively into the nude mouse model, subsequently, simultaneous SPECT/PET imaging was performed to calculate the tumour volume and tumour uptake of 99m Tc-3PRGD 2 and 18 F-FDG. The biodistribution study first validated that the tumour uptake of 99m Tc-3PRGD 2 at the different time points was higher than that of all the other organs tested in the experiment, except for the kidney. Integrin αvβ3 expressed highly in early stage HCC and declined for further necrosis of the tumour tissue. Subcutaneous tumours were visualized clearly with excellent contrast under 99m Tc-3PRGD 2 SPECT/CT imaging, and the multiphase imaging comparison showed the tumours were prominent at 0.5 h, suggesting that the best initial scan time is 0.5 h post-injection. The comparison of the imaging results of the two methods showed that 99m Tc-3PRGD 2 integrin receptor imaging was

A visual and semi-quantitative assessment of (99m)Tc-EDDA/HYNIC-TOC scintigraphy in differentiation of solitary pulmonary nodules.

PubMed

Płachcińska, Anna; Mikołajczak, Renata; Kozak, Józef; Rzeszutek, Katarzyna; Kuśmierek, Jacek

2004-01-01

The aim of the study was the assessment of the clinical usefulness of scintigraphy with (99m)Tc-EDDA/HYNIC-TOC for purposes of a differential diagnosis of SPNs by means of a visual inspection and semi-quantitative assessment of uptake intensity of the radiopharmaceutical (RPh). In 53 patients (32 males and 21 females at the ages between 38 and 78 years, mean value 57) with SPN on chest radiographs or CT scans, of diameters from 1 to 5.5 (mean 2.3) cm a SPECT acquisition was performed, 2-4 h after administration of 740 MBq of RPh. Additionally, aiming at the implementation of a correction of a partial volume effect resulting from finite resolution of this technique, the measurement of the resolution of this technique was performed on an thorax phantom. Scintigraphic studies were inspected visually visually and semi-quantitatively, restoring real concentration of the RPh in nodules in comparison with the peritumoral background (tumour-to-background ratio) by the application of resolution recovery coefficients for the respective nodule diameters. The threshold values of tumour-to-background ratio providing optimal differentiation between malignant and benign nodules of sizes smaller and larger than 2 cm in diameter were determined. Verification of scintigraphic results was based on pathological examinations of tumour samples (histopathology or cytology) and in some cases on bacteriological studies. The additional criterion of tumour benignity was accepted, based on its stable size in a time interval no shorter than 3 years. In 32 patients the following malignant tumours were diagnosed: 12 adenocarcinomas, 6 squamous cell carcinomas, 6 non-small cell lung cancers of unspecified more detailed morphology, 2 large cell carcinomas, 2 small cell lung cancers, 2 carcinoids and 2 metastatic lesions (malignant melanoma and leiomyosarcoma). In 21 patients benign etiologies were found: 6 tuberculomas, 2 other granuloma, 4 hamartomas, 2 non-specific inflammatory infiltrate, 1

Gd-EDDA/HYNIC-RGD as an MR molecular probe imaging integrin alphanubeta3 receptor-expressed tumor-MR molecular imaging of angiogenesis.

PubMed

Huo, Tianlong; Du, Xiangke; Zhang, Sen; Liu, Xia; Li, Xubing

2010-02-01

The aim of this study is to develop a novel MR probe containing arginine-glycine-aspartic acid (RGD) motif for imaging integrin alphanubeta3 receptor-expressed tumor. Commercially available HYNIC-RGD conjugated with co-ligand EDDA was labeled with Gd(3+), and the mixture was isolated and purified by solid phase extract (SPE) to get the entire probe Gd-EDDA/HYNIC-RGD. Human hepatocellular carcinoma (HHCC) cell line BEL-7402 was cultured and the cells harvested and suspended in serum-free Dulbecco's modified Eagle medium (DMEM) were subcutaneously inoculated into athymic nude mice for tumor growth. In vitro cell binding assay to integrin alphanubeta3 receptor and cell viability experiments were conducted. The in vivo imaging of the three arms of xenografts were performed by MR scan with a dedicated animal coil at time points of 0, 30, 60, 90min and 24-h post-intravenous injection (p.i.). Three arms of nude mice then were sacrificed for histological examination to confirm the imaging results. Gd-EDDA/HYNIC-RGD was successfully isolated by SPE and validity was verified on signal enhancement through in vitro and in vivo experiments. The nude mice model bearing HHCC was well established. There was approx. 30% signal enhancement on T1WI FSE images at 90min post-intravenous injection of the Gd-EDDA/HYNIC-RGD compared with baseline, and the signal to time curve is straightforward over time in the span of 0-90min p.i., while the control arms do not show this tendency. Gd-EDDA/HYNIC-RGD has the potential to serve as an MR probe detecting integrin alphanubeta3 receptor-expressed tumor. Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Synthesis and preliminary evaluation of radiolabeled bis(zinc(II)-dipicolylamine) coordination complexes as cell death imaging agents

PubMed Central

wyffels, Leonie; Gray, Brian D.; Barber, Christy; Woolfenden, James M.; Pak, Koon Y.; Liu, Zhonglin

2011-01-01

The aim of this study was the development of 99mTc labeled bis(zinc(II)-dipicolylamine) (Zn2+-DPA) coordination complexes, and the in vivo evaluation of their usefulness as radiotracers for the detection of cell death. DPA ligand 1 was labeled with 99mTc via the 99mTc-tricarbonyl core ([99mTc(CO)3-1]3+) or via HYNIC (99mTc-HYNIC-1) in good radiochemical yields. Highest in vitro stabilities were demonstrated for [99mTc(CO)3-1]3+. A mouse model of hepatic apoptosis (anti-Fas mAb) was used to demonstrate binding to apoptotic cells. 99mTc-HYNIC-1 showed the best targeting of apoptotic hepatic tissue with a 2.2 times higher liver uptake in anti-Fas treated mice as compared to healthy animals. A rat model of ischemia-reperfusion injury was used to further explore the ability of the 99mTc-labeled Zn2+-DPA coordination complexes to target cell death. Selective accumulation could be detected for both tracers in the area at risk, correlating with histological proof of cell death. Area at risk to normal tissue uptake ratios were 3.82 for [99mTc(CO)3-1]3+ and 5.45 for 99mTc-HYNIC-1. PMID:21570306

Effects of amino acids on melanoma targeting and clearance properties of Tc-99m-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone peptides.

PubMed

Flook, Adam M; Yang, Jianquan; Miao, Yubin

2013-11-14

The purpose of this study was to examine the effects of amino acids on melanoma targeting and clearance properties of new (99m)Tc-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-Lys-(Arg(11))CCMSH {c[Arg-Ser-Asp-DTyr-Asp]-Lys-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RNleD-Lys-(Arg(11))CCMSH, RPheD-Lys-(Arg(11))CCMSH, and RdPheD-Lys-(Arg(11))CCMSH peptides were synthesized and evaluated for their melanocortin-1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of (99m)Tc-RSD-Lys-(Arg(11))CCMSH, (99m)Tc-RFD-Lys-(Arg(11))CCMSH, and (99m)Tc-RfD-Lys-(Arg(11))CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The substitution of Gly with Ser, Phe, and dPhe increased the MC1 receptor binding affinities of the peptides, whereas the substitution of Gly with Nle decreased the MC1 receptor binding affinity of the peptide. (99m)Tc-RSD-Lys-(Arg(11))CCMSH exhibited the highest melanoma uptake (18.01 ± 4.22% ID/g) and the lowest kidney and liver uptake among these (99m)Tc-peptides. The B16/F1 melanoma lesions could be clearly visualized by SPECT/CT using (99m)Tc-RSD-Lys-(Arg(11))CCMSH as an imaging probe. It is desirable to reduce the renal uptake of (99m)Tc-RSD-Lys-(Arg(11))CCMSH to facilitate its potential therapeutic application.

Effects of Amino Acids on Melanoma Targeting and Clearance Properties of Tc-99m-Labeled Arg-X-Asp-Conjugated α-Melanocyte Stimulating Hormone Peptides

PubMed Central

Flook, Adam M.; Yang, Jianquan; Miao, Yubin

2013-01-01

The purpose of this study was to examine the effects of amino acids on melanoma targeting and clearance properties of new 99mTc-labeled Arg-X-Asp-conjugated alpha-melanocyte stimulating hormone (α-MSH) peptides. RSD-Lys-(Arg11)CCMSH {c[Arg-Ser-Asp-dTyr-Asp]-Lys-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RNleD-Lys-(Arg11)CCMSH, RPheD-Lys-(Arg11)CCMSH and RdPheD-Lys-(Arg11)CCMSH peptides were synthesized and evaluated for their melanocortin-1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of 99mTc-RSD-Lys-(Arg11)CCMSH, 99mTc-RFD-Lys-(Arg11)CCMSH and 99mTc-RfD-Lys-(Arg11)CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The substitution of Gly with Ser, Phe and dPhe increased the MC1 receptor binding affinities of the peptides, whereas the substitution of Gly with Nle decreased the MC1 receptor binding affinity of the peptide. 99mTc-RSD-Lys-(Arg11)CCMSH exhibited the highest melanoma uptake (18.01 ± 4.22% ID/g) and the lowest kidney and liver uptake among these 99mTc-peptides. The B16/F1 melanoma lesions could be clearly visualized by SPECT/CT using 99mTc-RSD-Lys-(Arg11)CCMSH as an imaging probe. It is desirable to reduce the renal uptake of 99mTc-RSD-Lys-(Arg11)CCMSH to facilitate its potential therapeutic application. PMID:24131154

In vitro cell studies of technetium-99m labeled RGD-HYNIC peptide, a comparison of tricine and EDDA as co-ligands.

PubMed

Su, Zi-Fen; He, Jiang; Rusckowski, Mary; Hnatowich, Donald J

2003-02-01

The level of alpha(V)beta(3) integrins on endothelial cells is elevated in angiogenesis. The high binding specificity to alpha(V)beta(3) integrins of peptides containing Arg-Gly-Asp (RGD) residues suggests that the radiolabeled RGD peptides may be useful as tumor specific imaging agents. In this research, cyclised peptides containing Arg-Gly-Asp (RGD) and Arg-Gly-Glu (RGE, as control) residues were conjugated with HYNIC and labeled with (99m)Tc. The goal was to evaluate the influence of co-ligand, either tricine or ethylenediamine-N,N'-diacetic acid (EDDA) on protein and integrin binding and on cellular uptake in culture. The n-octanol/water partition coefficient, binding to bovine serum albumin (BSA) and human umbilical vein endothelial (HUVE) cells, and cell lysate distributions of the radiolabeled peptides were evaluated. The co-ligands had a significant effect on the labeling efficiency of the HYNIC conjugates and on certain properties of the (99m)Tc complexes. The labeling efficiency with tricine was 10 fold higher and BSA binding was over 8 fold greater compared to EDDA. Both RGD labels showed higher (6 to 28 fold) binding to HUVE cells than that of the RGE labels, indicating binding specificity. After cell-lysis, only a small percentage of the total RGD label that accumulated in the cells was found bound to cellular proteins (9% of RGD/tricine and 5% of RGD/EDDA), implying that over 90% of the radiolabeled peptides were internalized for both radiolabeled RGDs. The number of the RGD molecules bound to proteins was estimated to be approximately three per cell, suggesting that only a small number of alpha(V)beta(3) integrin proteins are expressed on the cells. Apart from the differences in radiolabeling, the only important effect of substituting EDDA for tricine as co-ligand on the HYNIC-peptides was the lower degree of serum protein binding. In spite of the lower serum protein binding potential, in vivo tumor accumulation of the RGD/EDDA may not be improved

Polymorphism of DNA repair gene XPD Lys751Gln and chromosome aberrations in lymphocytes of thyroid cancer patients exposed to ionizing radiation due to the Chornobyl accident.

PubMed

Shkarupa, V M; Mishcheniuk, O Y; Henyk-Berezovska, S O; Palamarchuk, V O; Klymenko, S V

2016-12-01

The aim of this work was to analyze the relationship between polymorphisms of DNA repair gene XPD Lys751Gln and frequency and spectrum of chromosome aberrations in the culture of peripheral blood lymphocytes of thyroid cancer (TC) patients having been exposed to ionizing radiation due to the Chornobyl accident. XPD Lys751Gln polymorphisms were detected by polymerase chain reaction in 102 TC patients including 38 patients exposed to ionizing radiation due to Chornobyl disaster (Chornobyl recovery workers, evacuees, and the residents of contaminated areas), 64 patients without history of ionizing radiation exposure and 45 healthy residents of Ukraine as control group. In homozygous carriers of the minor allele XPD Gln751Gln, exposed to ionizing radiation, the significantly increased risk of TC (odds ratio = 3.66; p = 0.03; 95% confidence interval 1.04-12.84) was found. Among evacuees and residents of contaminated areas, homozygous carriers of the minor allele variants of XPD gene were characterized by the high level of spontaneous chromosome aberrations. TC patients without history of ionizing radiation exposure, being homozygous carriers of the allele XPD Lys751Lys, had significantly reduced frequency of chromosome-type aberrations. The carriage of homozygous minor allele of DNA repair gene XPD Gln751Gln is a risk factor for TC in persons from Ukrainian population exposed to ionizing radiation and is associated with the increased levels of chromosomal instability. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

In Vitro Study of Bacteriophage AB3 Endolysin LysAB3 Activity Against Acinetobacter baumannii Biofilm and Biofilm-Bound A. baumannii.

PubMed

Zhang, Jie; Xu, Lu-Lu; Gan, Dan; Zhang, Xingping

2018-06-01

The increase in the prevalence of drug-resistant Acinetobacter baumannii is a serious public health concern, which is closely linked to the formation of biofilm. It is reported that the bacteriophage and its endolysin have a good ability to degrade biofilms. The goals of this study were to compare the ability of A. baumannii bacteriophage AB3, its endolysin AB3, and three antibiotics to degrade A. baumannii biofilm and biofilm-bound A. baumannii and to understand the antibacterial mechanism of LysAB3. The 558-bp sequence of the LysAB3 gene was amplified by polymerase chain reaction (PCR); the fragment was cloned into pET28a (+) to construct the recombinant plasmid pET28a-LysAB3, which was then expressed in E. coli BL21 (DE3) to obtain the LysAB3. Differences in A. baumannii biofilm and biofilm-bound A. baumannii after treatment with bacteriophage AB3, LysAB3 or three antibiotics were examined using the crystal violet staining method and an MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide) assay. Changes in biofilm morphology and thickness in each treatment group were observed by laser scanning confocal microscopy. In addition, a LysAB3 construct with the amphiphilic peptide structural region removed (LysAB3-D) was assessed for its antibacterial activity. After 24-hour treatment with either bacteriophage AB3 and its LysAB3, A. baumannii biofilms were significantly degraded, and the number of viable biofilm-bound A. baumannii were also significantly decreased. After removing the amphiphilic peptide structure motif from LysAB3, the antibacterial activity decreased from 95.8% to 33.3%. Thus, LysAB3 can effectively degrade A. baumannii biofilm and biofilm-bound A. baumannii in vitro. The antibacterial mechanism of LysAB3 may be associated with the ability of the amphiphilic peptide structural region to enhance the permeability of cytoplasmic membrane of A. baumannii by degradation of bacterial wall peptidoglycan.

Incorporation of excess wild-type and mutant tRNA(3Lys) into human immunodeficiency virus type 1.

PubMed Central

Huang, Y; Mak, J; Cao, Q; Li, Z; Wainberg, M A; Kleiman, L

1994-01-01

Human immunodeficiency virus (HIV) particles produced in COS-7 cells transfected with HIV type 1 (HIV-1) proviral DNA contain 8 molecules of tRNA(3Lys) per 2 molecules of genomic RNA and 12 molecules of tRNA1,2Lys per 2 molecules of genomic RNA. When COS-7 cells are transfected with a plasmid containing both HIV-1 proviral DNA and a human tRNA3Lys gene, there is a large increase in the amount of cytoplasmic tRNA3Lys per microgram of total cellular RNA, and the tRNA3Lys content in the virus increases from 8 to 17 molecules per 2 molecules of genomic RNA. However, the total number of tRNALys molecules per 2 molecules of genomic RNA remains constant at 20; i.e., the viral tRNA1,2Lys content decreases from 12 to 3 molecules per 2 molecules of genomic RNA. All detectable tRNA3Lys is aminoacylated in the cytoplasm of infected cells and deacylated in the virus. When COS-7 cells are transfected with a plasmid containing both HIV-1 proviral DNA and a mutant amber suppressor tRNA3Lys gene (in which the anticodon is changed from TTT to CTA), there is also a large increase in the relative concentration of cytoplasmic tRNA3Lys, and the tRNA3Lys content in the virus increases from 8 to 15 molecules per 2 molecules of genomic RNA, with a decrease in viral tRNA1,2Lys from 12 to 5 molecules per 2 molecules of genomic RNA. Thus, the total number of molecules of tRNALys in the virion remains at 20. The alteration of the anticodon has little effect on the viral packaging of this mutant tRNA in spite of the fact that it no longer contains the modified base mcm 5s2U at position 34, and its ability to be aminoacylated is significantly impaired compared with that of wild-type tRNA3Lys. Viral particles which have incorporated either excess wild-type tRNA3Lys or mutant suppressor tRNA3Lys show no differences in viral infectivity compared with wild-type HIV-1. Images PMID:7966556

Radiolabeled Rhein as Small-Molecule Necrosis Avid Agents for Imaging of Necrotic Myocardium.

PubMed

Luo, Qi; Jin, Qiaomei; Su, Chang; Zhang, Dongjian; Jiang, Cuihua; Fish, Anne Folta; Feng, Yuanbo; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

2017-01-17

A rapid and accurate identification of necrotic myocardium is of great importance for diagnosis, risk stratification, clinical decision-making, and prognosis evaluation of myocardial infarction. Here, we explored technetium-99m labeled rhein derivatives for rapid imaging of the necrotic myocardium. Three hydrazinonicotinic acid-linker-rhein (HYNIC-linker-rhein) derivatives were synthesized, and then, these synthetic compounds were labeled with technetium-99m using ethylenediaminediacetic acid (EDDA) and tricine as coligands [ 99m Tc(EDDA)-HYNIC-linker-rhein]. The necrosis avidity of the three 99m Tc-labeled rhein derivatives was tested in a mouse model of ethanol-induced muscular necrosis by gamma counting, histochemical staining, and autoradiography. A lead tracer for visualization of necrotic myocardium was assessed by single photon emission computed tomography/computed tomography (SPECT/CT) imaging in a rat model with reperfused myocardial infarction. The necrosis avidity mechanism of the tracer was explored by DNA binding studies in vitro and blocking experiments in vivo. Results showed that the uptake in necrotic muscles of the three 99m Tc-compounds was higher than that in viable muscles (P < 0.001). Autoradiography and histochemical staining results were consistent with selective uptake of the radiotracer in the necrotic regions. Among the these tracers, 99m Tc(EDDA)-HYNIC-ethylenediamine-rhein [ 99m Tc(EDDA)-HYNIC-2C-rhein] displayed the best distribution profiles for imaging. The necrotic myocardium lesions were clearly visualized by SPECT/CT using 99m Tc(EDDA)-HYNIC-2C-rhein at 1 h after injection. The necrotic-to-viable myocardium and necrotic myocardium-to-blood uptake ratios of 99m Tc(EDDA)-HYNIC-2C-rhein were 4.79 and 3.02 at 1 h after injection. DNA binding studies suggested HYNIC-linker-rhein bound to DNA through intercalation. The uptake of 99m Tc(EDDA)-HYNIC-2C-rhein in necrotic muscle was significantly blocked by excessive unlabeled rhein, with

Pressure sensing element based on the BN-graphene-BN heterostructure

NASA Astrophysics Data System (ADS)

Li, Mengwei; Wu, Chenggen; Zhao, Shiliang; Deng, Tao; Wang, Junqiang; Liu, Zewen; Wang, Li; Wang, Gao

2018-04-01

In this letter, we report a pressure sensing element based on the graphene-boron nitride (BN) heterostructure. The heterostructure consists of monolayer graphene sandwiched between two layers of vertically stacked dielectric BN nanofilms. The BN layers were used to protect the graphene layer from oxidation and pollution. Pressure tests were performed to investigate the characteristics of the BN-graphene-BN pressure sensing element. A sensitivity of 24.85 μV/V/mmHg is achieved in the pressure range of 130-180 kPa. After exposing the BN-graphene-BN pressure sensing element to the ambient environment for 7 days, the relative resistance change in the pressure sensing element is only 3.1%, while that of the reference open-faced graphene device without the BN protection layers is 15.7%. Thus, this strategy is promising for fabricating practical graphene pressure sensors with improved performance and stability.

Optimization of image reconstruction method for SPECT studies performed using [⁹⁹mTc-EDDA/HYNIC] octreotate in patients with neuroendocrine tumors.

PubMed

Sowa-Staszczak, Anna; Lenda-Tracz, Wioletta; Tomaszuk, Monika; Głowa, Bogusław; Hubalewska-Dydejczyk, Alicja

2013-01-01

Somatostatin receptor scintigraphy (SRS) is a useful tool in the assessment of GEP-NET (gastroenteropancreatic neuroendocrine tumor) patients. The choice of appropriate settings of image reconstruction parameters is crucial in interpretation of these images. The aim of the study was to investigate how the GEP NET lesion signal to noise ratio (TCS/TCB) depends on different reconstruction settings for Flash 3D software (Siemens). SRS results of 76 randomly selected patients with confirmed GEP-NET were analyzed. For SPECT studies the data were acquired using standard clinical settings 3-4 h after the injection of 740 MBq 99mTc-[EDDA/HYNIC] octreotate. To obtain final images the OSEM 3D Flash reconstruction with different settings and FBP reconstruction were used. First, the TCS/TCB ratio in voxels was analyzed for different combinations of the number of subsets and the number of iterations of the OSEM 3D Flash reconstruction. Secondly, the same ratio was analyzed for different parameters of the Gaussian filter (with FWHM = 2-4 times greater from the pixel size). Also the influence of scatter correction on the TCS/TCB ratio was investigated. With increasing number of subsets and iterations, the increase of TCS/TCB ratio was observed. With increasing settings of Gauss [FWHM coefficient] filter, the decrease of TCS/TCB ratio was reported. The use of scatter correction slightly decreases the values of this ratio. OSEM algorithm provides a meaningfully better reconstruction of the SRS SPECT study as compared to the FBP technique. A high number of subsets improves image quality (images are smoother). Increasing number of iterations gives a better contrast and the shapes of lesions and organs are sharper. The choice of reconstruction parameters is a compromise between image qualitative appearance and its quantitative accuracy and should not be modified when comparing multiple studies of the same patient.

Multi-Functional BN-BN Composite

NASA Technical Reports Server (NTRS)

Kang, Jin Ho (Inventor); Bryant, Robert G. (Inventor); Park, Cheol (Inventor); Sauti, Godfrey (Inventor); Gibbons, Luke (Inventor); Lowther, Sharon (Inventor); Thibeault, Sheila A. (Inventor); Fay, Catharine C. (Inventor)

2017-01-01

Multifunctional Boron Nitride nanotube-Boron Nitride (BN-BN) nanocomposites for energy transducers, thermal conductors, anti-penetrator/wear resistance coatings, and radiation hardened materials for harsh environments. An all boron-nitride structured BN-BN composite is synthesized. A boron nitride containing precursor is synthesized, then mixed with boron nitride nanotubes (BNNTs) to produce a composite solution which is used to make green bodies of different forms including, for example, fibers, mats, films, and plates. The green bodies are pyrolized to facilitate transformation into BN-BN composite ceramics. The pyrolysis temperature, pressure, atmosphere and time are controlled to produce a desired BN crystalline structure. The wholly BN structured materials exhibit excellent thermal stability, high thermal conductivity, piezoelectricity as well as enhanced toughness, hardness, and radiation shielding properties. By substituting with other elements into the original structure of the nanotubes and/or matrix, new nanocomposites (i.e., BCN, BCSiN ceramics) which possess excellent hardness, tailored photonic bandgap and photoluminescence, result.

Melanoma targeting with alpha-melanocyte stimulating hormone analogs labeled with fac-[99mTc(CO)3]+: effect of cyclization on tumor-seeking properties.

PubMed

Raposinho, Paula D; Xavier, Catarina; Correia, João D G; Falcão, Soraia; Gomes, Paula; Santos, Isabel

2008-03-01

Early detection of primary melanoma tumors is essential because there is no effective treatment for metastatic melanoma. Several linear and cyclic radiolabeled alpha-melanocyte stimulating hormone (alpha-MSH) analogs have been proposed to target the melanocortin type 1 receptor (MC1R) overexpressed in melanoma. The compact structure of a rhenium-cyclized alpha-MSH analog (Re-CCMSH) significantly enhanced its in vivo tumor uptake and retention. Melanotan II (MT-II), a cyclic lactam analog of alpha-MSH (Ac-Nle-cyclo[Asp-His-DPhe-Arg-Trp-Lys]-NH2]), is a very potent and stable agonist peptide largely used in the characterization of melanocortin receptors. Taking advantage of the superior biological features associated with the MT-II cyclic peptide, we assessed the effect of lactam-based cyclization on the tumor-seeking properties of alpha-MSH analogs by comparing the pharmacokinetics profile of the 99mTc-labeled cyclic peptide betaAla-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 with that of the linear analog betaAla-Nle-Asp-His-DPhe-Arg-Trp-Lys-NH2 in melanoma-bearing mice. We have synthesized and coupled the linear and cyclic peptides to a bifunctional chelator containing a pyrazolyl-diamine backbone (pz) through the amino group of betaAla, and the resulting pz-peptide conjugates were reacted with the fac-[99mTc(CO)3]+ moiety. The 99mTc(CO)3-labeled conjugates were obtained in high yield, high specific activity, and high radiochemical purity. The cyclic 99mTc(CO)3-labeled conjugate presents a remarkable internalization (87.1% of receptor-bound tracer and 50.5% of total applied activity, after 6 h at 37 degrees C) and cellular retention (only 24.7% released from the cells after 5 h) in murine melanoma B16F1 cells. A significant tumor uptake and retention was obtained in melanoma-bearing C57BL6 mice for the cyclic radioconjugate [9.26 +/- 0.83 and 11.31 +/- 1.83% ID/g at 1 and 4 h after injection, respectively]. The linear 99mTc(CO)3-pz-peptide presented lower values for

99mTc-EDDA/HYNIC-Tyr(3)-octreotide for staging and follow-up of patients with neuroendocrine gastro-entero-pancreatic tumors.

PubMed

Gabriel, M; Muehllechner, P; Decristoforo, C; von Guggenberg, E; Kendler, D; Prommegger, R; Profanter, C; Moncayo, R; Virgolini, I

2005-09-01

To evaluate the use of 99mTc-EDDA-hydrazinonicotinyl-Tyr3-octreotide (Tc-TOC) for staging and follow-up of neuroendocrine gastro-entero-pancreatic (GEP) tumors with special focus on the acquisition protocol including single photon emission computed tomography (SPECT). Eighty-eight patients (37 female, 51 male; age range: 16 to 81 years; mean age: 56.3 years) were studied: 42 patients for staging after initial histological confirmation and 46 patients during post-therapy follow-up. An average activity of 400 MBq of the radiopharmaceutical was injected. All tumors originated from neuroendocrine tissue of the gastroenteropancreatic tract. Whole body scintigrams at 4 h postinjection and SPECT of the abdomen were obtained in all patients. Additional planar images of the abdomen were acquired at 2 h after injection in 68 patients. The Tc-TOC scan result was true-positive in 56 patients, true-negative in 17, false-negative in 14, and false-positive in 1 patient. The false-positive finding was caused by a colonic adenoma. Overall, a scan sensitivity of 80% (56/70 patients), specificity of 94.4% (17/18 patients) and accuracy of 82.9% (73/88 patients) were calculated on patient basis. In total, Tc-TOC detected 357 foci in 69 patients. In 7 patients equivocal findings were observed in the bowel at 4 h postinjection without corresponding tracer uptake in the scan 2 h earlier, meaning that these abnormal findings were correctly classified as non-malignant. In addition to planar views, SPECT revealed further 62 lesions. Tc-TOC with one-day, dual-time acquisition protocol is an accurate staging procedure in patients with neuroendocrine GEP tumors. SPECT shows high sensitivity for detection of abdominal lesions, while earlier images improve the reliability of abnormal abdominal findings.

BnSGS3 Has Differential Effects on the Accumulation of CMV, ORMV and TuMV in Oilseed Rape

PubMed Central

Chen, Quan; Wang, Jie; Hou, Mingsheng; Liu, Shengyi; Huang, Junyan; Cai, Li

2015-01-01

Virus diseases greatly affect oilseed rape (Brassica napus) production. Investigating antiviral genes may lead to the development of disease-resistant varieties of oilseed rape. In this study, we examined the effects of the suppressor of gene silencing 3 in Brassica napus (BnSGS3, a putative antiviral gene) with different genus viruses by constructing BnSGS3-overexpressing (BnSGS3-Ov) and BnSGS3-silenced (BnSGS3-Si) oilseed rape (cv. Zhongshuang No. 6) plants. These three viruses are Oilseed rape mosaic virus (ORMV), Turnip mosaic virus (TuMV) and Cucumber mosaic virus (CMV). The native BnSGS3 expressed in all examined tissues with the highest expression in siliques. All three viruses induced BnSGS3 expression, but ORMV induced a dramatic increase in the BnSGS3-Ov plants, followed by TuMV and CMV. Upon inoculation with three different viruses, transcript abundance of BnSGS3 gene follows: BnSGS3-Ov > non-transgenic plants > BnSGS3-Si. The accumulation quantities of ORMV and TuMV exhibited a similar trend. However, CMV accumulation showed an opposite trend where virus accumulations were negatively correlated with BnSGS3 expression. The results suggest that BnSGS3 selectively inhibits CMV accumulation but promotes ORMV and TuMV accumulation. BnSGS3 should be used in different ways (up- and down-regulation) for breeding virus-resistant oilseed rape varieties. PMID:26225990

111In-BnDTPA-F3: an Auger electron-emitting radiotherapeutic agent that targets nucleolin

PubMed Central

2012-01-01

Introduction The F3 peptide (KDEPQRRSARLSAKPAPPKPEPKPKKAPAKK), a fragment of the human high mobility group protein 2, binds nucleolin. Nucleolin is expressed in the nuclei of normal cells but is also expressed on the membrane of some cancer cells. The goal was to investigate the use of 111In-labeled F3 peptide for Auger electron-targeted radiotherapy. Methods F3 was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy and conjugated to p-SCN-benzyl-diethylenetriaminepentaacetic acid (BnDTPA) for labeling with 111In to form 111In-BnDTPA-F3. MDA-MB-231-H2N (231-H2N) human breast cancer cells were exposed to 111In-BnDTPA-F3 and used in cell fractionation, γH2AX immunostaining (a marker of DNA double-strand breaks), and clonogenic assays. In vivo, biodistribution studies of 111In-BnDTPA-F3 were performed in 231-H2N xenograft-bearing mice. In tumor growth delay studies, 111In-BnDTPA-F3 (3 μg, 6 MBq/μg) was administered intravenously to 231-H2N xenograft-bearing mice once weekly for 3 weeks. Results Membrane-binding of FITC-F3 was observed in 231-H2N cells, and there was co-localization of FITC-F3 with nucleolin in the nuclei. After exposure of 231-H2N cells to 111In-BnDTPA-F3 for 2 h, 1.7% of 111In added to the medium was membrane-bound. Of the bound 111In, 15% was internalized, and of this, 37% was localized in the nucleus. Exposure of 231-H2N cells to 111In-BnDTPA-F3 (1 μM, 6 MBq/μg) resulted in a dose-dependent increase in γH2AX foci and in a significant reduction of clonogenic survival compared to untreated cells or cells exposed to unlabeled BnDTPA-F3 (46 ± 4.1%, 100 ± 1.8%, and 132 ± 7.7%, respectively). In vivo, tumor uptake of 111In-BnDTPA-F3 (3 μg, 6 MBq/μg) at 3-h post-injection was 1% of the injected dose per gram (%ID/g), and muscle uptake was 0.5%ID/g. In tumor growth delay studies, tumor growth rate was reduced 19-fold compared to untreated or unlabeled BnDTPA-F3-treated mice (p = 0.023). Conclusion 111In-BnDTPA-F3 is

111In-BnDTPA-F3: an Auger electron-emitting radiotherapeutic agent that targets nucleolin.

PubMed

Cornelissen, Bart; Waller, Andrew; Target, Carol; Kersemans, Veerle; Smart, Sean; Vallis, Katherine A

2012-02-20

The F3 peptide (KDEPQRRSARLSAKPAPPKPEPKPKKAPAKK), a fragment of the human high mobility group protein 2, binds nucleolin. Nucleolin is expressed in the nuclei of normal cells but is also expressed on the membrane of some cancer cells. The goal was to investigate the use of 111In-labeled F3 peptide for Auger electron-targeted radiotherapy. F3 was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy and conjugated to p-SCN-benzyl-diethylenetriaminepentaacetic acid (BnDTPA) for labeling with 111In to form 111In-BnDTPA-F3. MDA-MB-231-H2N (231-H2N) human breast cancer cells were exposed to 111In-BnDTPA-F3 and used in cell fractionation, γH2AX immunostaining (a marker of DNA double-strand breaks), and clonogenic assays. In vivo, biodistribution studies of 111In-BnDTPA-F3 were performed in 231-H2N xenograft-bearing mice. In tumor growth delay studies, 111In-BnDTPA-F3 (3 μg, 6 MBq/μg) was administered intravenously to 231-H2N xenograft-bearing mice once weekly for 3 weeks. Membrane-binding of FITC-F3 was observed in 231-H2N cells, and there was co-localization of FITC-F3 with nucleolin in the nuclei. After exposure of 231-H2N cells to 111In-BnDTPA-F3 for 2 h, 1.7% of 111In added to the medium was membrane-bound. Of the bound 111In, 15% was internalized, and of this, 37% was localized in the nucleus. Exposure of 231-H2N cells to 111In-BnDTPA-F3 (1 μM, 6 MBq/μg) resulted in a dose-dependent increase in γH2AX foci and in a significant reduction of clonogenic survival compared to untreated cells or cells exposed to unlabeled BnDTPA-F3 (46 ± 4.1%, 100 ± 1.8%, and 132 ± 7.7%, respectively). In vivo, tumor uptake of 111In-BnDTPA-F3 (3 μg, 6 MBq/μg) at 3-h post-injection was 1% of the injected dose per gram (%ID/g), and muscle uptake was 0.5%ID/g. In tumor growth delay studies, tumor growth rate was reduced 19-fold compared to untreated or unlabeled BnDTPA-F3-treated mice (p = 0.023). 111In-BnDTPA-F3 is internalized into 231-H2N cells and translocates

Boron Nitride Obtained from Molecular Precursors: Aminoboranes Used as a BN Source for Coatings, Matrix, and Si 3N 4-BN Composite Ceramic Preparation

NASA Astrophysics Data System (ADS)

Thévenot, F.; Doche, C.; Mongeot, H.; Guilhon, F.; Miele, P.; Cornu, D.; Bonnetot, B.

1997-10-01

Aminoboranes, pure or partially converted into aminoborazines using thermal or aminolysis polymerization, have been used as boron nitride precursors. An amorphous BN preceramic is obtained when pyrolysed up to 1000°C that can be stabilized using further annealing up to 1400°C or crystallized into h-BN above 1700°C. These molecular precursors have been used to prepare carbon fiber/BN matrix microcomposites to get an efficient BN coating on graphite and as a BN source in Si3N4/BN composite ceramic. The properties of these new types of samples have been compared with those obtained by classical processes. The boron nitride obtained from these precursors is a good sintering agent during the hot-pressing of the samples. However, the crystallinity of BN, even sintered up to 1800°C, remains poor. In fact, most of the mechanical properties of the composite ceramic (density, porosity, hardness) are clearly improved and the aminoboranes can be considered as convenient boron nitride sources and helpful sintering agents in hot-pressing technology.

Investigation of SP94 Peptide as a Specific Probe for Hepatocellular Carcinoma Imaging and Therapy

PubMed Central

Li, Yanli; Hu, Yan; Xiao, Jie; Liu, Guobing; Li, Xiao; Zhao, Yanzhao; Tan, Hui; Shi, Hongcheng; Cheng, Dengfeng

2016-01-01

SP94 (SFSIIHTPILPL), a novel peptide, has shown specific binding to hepatocellular carcinoma (HCC) cells. We aimed to investigate the capability of SP94 as a targeting probe for HCC imaging and therapy following labeling with technetium-99m (99mTc) and rhenium-188 (188Re). HYNIC-SP94 was prepared by solid phase synthesis and then labeled with 99mTc. Cell competitive binding, internalization assay, in vitro and in vivo stability, biodistribution and micro-single photon emission computed tomography /computed tomography (SPECT/CT) imaging studies were performed to investigate the capability of 99mTc tricine-EDDA/HYNIC-SP94 as a specific HCC imaging probe. Initial promising targeting results inspired evaluation of its therapeutic effect when labeled by 188Re. HYNIC-SP94 was then labeled again with 188Re to perform cell apoptosis, microSPECT/CT imaging evaluation and immunohistochemistry. Huh-7 cells exhibited typical apoptotic changes after 188Re irradiation. According to 99mTc tricine-EDDA/HYNIC-SP94 microSPECT/CT imaging, tumor uptake was significantly decreased compared with that of pre-treatment with 188Re-HYNIC-SP94. The immunohistochemistry also displayed obvious necrosis and apoptosis as well as inhibition of proliferation in the 188Re-HYNIC-SP94 treatment group. The results supported that 99mTc tricine-EDDA/HYNIC-SP94 is able to target HCC cells and 188Re-HYNIC- SP94 holds potential as a therapeutic agent for HCC, making 99mTc/188Re-HYNIC-SP94 a promising targeting probe for HCC imaging and therapy. PMID:27649935

Direct conversion of h-BN into c-BN and formation of epitaxial c-BN/diamond heterostructures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Narayan, Jagdish, E-mail: narayan@ncsu.edu; Bhaumik, Anagh; Xu, Weizong

2016-05-14

We have created a new state of BN (named Q-BN) through rapid melting and super undercooling and quenching by using nanosecond laser pulses. Phase pure c-BN is formed either by direct quenching of super undercooled liquid or by nucleation and growth from Q-BN. Thus, a direct conversion of hexagonal boron nitride (h-BN) into phase-pure cubic boron nitride (c-BN) is achieved by nanosecond pulsed laser melting at ambient temperatures and atmospheric pressure in air. According to the P-T phase diagram, the transformation from h-BN into c-BN under equilibrium processing can occur only at high temperatures and pressures, as the hBN-cBN-Liquid triplemore » point is at 3500 K/9.5 GPa or 3700 K/7.0 GPa with a recent theoretical refinement. Using nonequilibrium nanosecond laser melting, we have created super undercooled state and shifted this triple point to as low as 2800 K and atmospheric pressure. The rapid quenching from super undercooled state leads to the formation of a new phase, named as Q-BN. We present detailed characterization of Q-BN and c-BN layers by using Raman spectroscopy, high-resolution scanning electron microscopy, electron-back-scatter diffraction, high-resolution TEM, and electron energy loss spectroscopy, and discuss the mechanism of formation of nanodots, nanoneedles, microneedles, and single-crystal c-BN on sapphire substrate. We have also deposited diamond by pulsed laser deposition of carbon on c-BN and created c-BN/diamond heterostructures, where c-BN acts as a template for epitaxial diamond growth. We discuss the mechanism of epitaxial c-BN and diamond growth on lattice matching c-BN template under pulsed laser evaporation of amorphous carbon, and the impact of this discovery on a variety of applications.« less

Synthesis and processing of nanostructured BN and BN/Ti composites

NASA Astrophysics Data System (ADS)

Horvath, Robert Steven

Superhard materials, such as cubic-BN, are widely used in machine tools, grinding wheels, and abrasives. Low density combined with high hardness makes c-BN and its composites attractive candidate materials for personnel and vehicular armor. However, improvements in toughness, and ballistic-impact performance, are needed to meet anticipated performance requirements. To achieve such improvements, we have targeted for development nanostructured c-BN, and its composites with Ti. Current research utilizes an experimental high pressure/high temperature (HPHT) method to produce these materials on a laboratory scale. Results from this work should transfer well into the industrial arena, utilizing high-tonnage presses used in the production of synthetic diamond and c-BN. Progress has been made in: (1) HPHT synthesis of cBN powder using Mg as catalyst; (2) HPHT consolidation of cBN powder to produce nanostructured cBN; (3) reactive-HPHT consolidation of mixed cBN/Ti powder to produce nanostructured Ti- or TiB2/TiN-bonded cBN; and (4) reactive-HPHT consolidation of mixed hBN/Ti powder to produce nanostructured Ti-bonded TiB2/TiN or TiB2/TiN. Even so, much remains to be done to lay a firm scientific foundation to enable the reproducible fabrication of large-area panels for armor applications. To this end, Rutgers has formed a partnership with a major producer of hard and superhard materials. The ability to produce hard and superhard nanostructured composites by reacting cBN or hBN with Ti under high pressure also enables multi-layered structures to be developed. Such structures may be designed to satisfy impedance-mismatch requirements for high performance armor, and possibly provide a multi-hit capability. A demonstration has been made of reactive-HPHT processing of multi-layered composites, consisting of alternating layers of superhard Ti-bonded cBN and tough Ti. It is noteworthy that the pressure requirements for processing Ti-bonded cBN, Ti-bonded TiB2/TiN, and their

Template-Free Synthesis of Functional 3D BN architecture for removal of dyes from water

PubMed Central

Liu, Dan; Lei, Weiwei; Qin, Si; Chen, Ying

2014-01-01

Three-dimensional (3D) architectures are of interest in applications in electronics, catalysis devices, sensors and adsorption materials. However, it is still a challenge to fabricate 3D BN architectures by a simple method. Here, we report the direct synthesis of 3D BN architectures by a simple thermal treatment process. A 3D BN architecture consists of an interconnected flexible network of nanosheets. The typical nitrogen adsorption/desorption results demonstrate that the specific surface area for the as-prepared samples is up to 1156 m2 g−1, and the total pore volume is about 1.17 cm3 g−1. The 3D BN architecture displays very high adsorption rates and large capacities for organic dyes in water without any other additives due to its low densities, high resistance to oxidation, good chemical inertness and high surface area. Importantly, 88% of the starting adsorption capacity is maintained after 15 cycles. These results indicate that the 3D BN architecture is potential environmental materials for water purification and treatment. PMID:24663292

Template-free synthesis of functional 3D BN architecture for removal of dyes from water.

PubMed

Liu, Dan; Lei, Weiwei; Qin, Si; Chen, Ying

2014-03-25

Three-dimensional (3D) architectures are of interest in applications in electronics, catalysis devices, sensors and adsorption materials. However, it is still a challenge to fabricate 3D BN architectures by a simple method. Here, we report the direct synthesis of 3D BN architectures by a simple thermal treatment process. A 3D BN architecture consists of an interconnected flexible network of nanosheets. The typical nitrogen adsorption/desorption results demonstrate that the specific surface area for the as-prepared samples is up to 1156 m(2) g(-1), and the total pore volume is about 1.17 cm(3) g(-1). The 3D BN architecture displays very high adsorption rates and large capacities for organic dyes in water without any other additives due to its low densities, high resistance to oxidation, good chemical inertness and high surface area. Importantly, 88% of the starting adsorption capacity is maintained after 15 cycles. These results indicate that the 3D BN architecture is potential environmental materials for water purification and treatment.

Biokinetics and dosimetry of several radiolabelled peptides in cancer cells

NASA Astrophysics Data System (ADS)

Rodríguez-Cortés, J.; Ferro-Flores, G.; de Murphy, C. Arteaga; Pedraza-López, M.; Ramírez-Iglesias, M. A. T.

Radiolabelled peptides have been used as target-specific radiopharmaceuticals. The goal of this research was the in vitro assessment of the uptake, internalization, externalization, and efflux of five radiolabelled peptides in cancer cells to estimate radiation-absorbed doses from experimental biokinetic data. 177Lu-DOTA-octreotate, 188Re-lanreotide, and 99mTc-HYNIC-octreotide were studied in the AR42J cell line. The PC3 and NCIH69 cells were used for 99mTc-HYNIC-bombesin and 177Lu-DOTA-minigastrin, respectively. The cumulated activities in the membrane and cytoplasm were calculated by integration of the experimental time-activity curves and used for dosimetry calculations according to the Medical Internal Radiation Dose (MIRD) cellular methodology. The mean absorbed dose to the cell nucleus were 0.69±0.09, 0.11±0.08, 0.55±0.09, 3.45±0.48, and 3.30±0.65 Gy/Bq for 99mTc-HYNIC-bombesin, 99mTc-HYNIC-octreotide, 177Lu-DOTA-minigastrin, 177Lu-DOTA-octreotate, and 188Re-lanreotide, respectively. If radiopharmaceutical cell kinetics were not used and only uptake data were considered, the calculated doses would be overestimated up to 25 times.

Inactivation of chloroplast H(+)-ATPase by modification of Lys beta 359, Lys alpha 176 and Lys alpha 266.

PubMed

Horbach, M; Meyer, H E; Bickel-Sandkötter, S

1991-09-01

Treatment of isolated, latent chloroplast ATPase with pyridoxal-5-phosphate (pyridoxal-P) in presence of Mg2+ causes inhibition of dithiothreitol-activated plus heat-activated ATP hydrolysis. The amount of [3H]pyridoxal-P bound to chloroplast coupling factor 1 (CF1) was estimated to run up to 6 +/- 1 pyridoxal-P/enzyme, almost equally distributed between the alpha- and beta-subunits. Inactivation, however, is complete after binding of 1.5-2 pyridoxal-P/CF1, suggesting that two covalently modified lysines prevent the activation of the enzyme. ADP as well as ATP in presence of Mg2+ protects the enzyme against inactivation and concomittantly prevents incorporation of a part of the 3H-labeled pyridoxal-P into beta- and alpha-subunits. Phosphate prevents labeling of the alpha-subunit, but has only a minor effect on protection against inactivation. The data indicate a binding site at the interface between the alpha- and beta-subunits. Cleavage of the pyridoxal-P-labeled subunits with cyanogen bromide followed by sequence analysis of the labeled peptides led to the detection of Lys beta 359, Lys alpha 176 and Lys alpha 266, which are closely related to proposed nucleotide-binding regions of the alpha- and beta-subunits.

Bn and Si-Doped Bn Coatings on Woven Fabrics

NASA Technical Reports Server (NTRS)

Hurwitz, Frances I.; Scott, John M.; Wheeler, Donald R.; Chayka, Paul V.; Gray, Hugh R. (Technical Monitor)

2002-01-01

A computer controlled, pulsed chemical vapor infiltration (CVI) system has been developed to deposit BN from a liquid borazine (B3N3H6) source, as well as silicon doped BN coatings using borazine and a silicon source, into 2-D woven ceramic fabric preforms. The coating process was evaluated as a function of deposition temperature, pressure, and precursor flow rate. Coatings were characterized by field emission scanning electron microscopy, electron dispersive spectroscopy and Auger spectroscopy. By controlling the reactant feed ratios, Si incorporation could be controlled over the range of 6-24 atomic percent.

Progress on BN and Doped-BN Coatings on Woven Fabrics

NASA Technical Reports Server (NTRS)

Hurwitz, Frances I.; Scott, John M.; Chayka, Paul V.

2001-01-01

A novel, multistep process for applying interface coatings to woven structures using a pulsed CVD process is being evaluated. Borazine (B3N3H6), a neat liquid, and several Si precursors are used in the process to produce BN and SiBN coatings on Hi- Nicalon fabrics and preforms. A three variable, two level, full factorial matrix is proposed to define the influence of processing parameters. Coating morphology, uniformity and chemistry are characterized by field emission scanning electron microscopy (FESEM), energy dispersive (EDS) and Auger spectroscopies.

/sup 3/H-PAF-acether displacement and inhibition of binding in intact human platelets by BN 52021

DOE Office of Scientific and Technical Information (OSTI.GOV)

Korth, R.; Le Couedic, J.P.; Benveniste, J.

1986-03-05

Intact washed human platelets incubated at 20/sup 0/C in Tyrode's buffer containing 0.25% (w/v) bovine serum albumin bound /sup 3/H paf-acether in a concentration (0-6.5 nM) and time (0-60 min) dependent manner (n=3). BN 52021 (60 ..mu..M) a chemically defined extract from Ginkgo biloba inhibited the binding of increasing concentrations of /sup 3/H paf-acether. Calculated differences between /sup 3/H paf-acether binding in the presence or absence of BN 52021 (60 ..mu..M) reached nearly a plateau in concentrations higher than 0.65 nM /sup 3/H paf-acether. Increasing concentrations of BN 52021 (0-60 ..mu..M) as well as of unlabelled paf-acether (0-50 nM) preventedmore » within 15 min /sup 3/H paf-acether binding (0.65 nM) to platelets in a concentration-dependent way. Increasing BN 52021 concentrations (0-60 ..mu..M) also displaced platelet-bound /sup 3/H paf-acether (0.65 nM) in a concentration-dependent way. Displacement increased with the time length of platelet incubation with BN 52021 and reached a plateau at 15 min. Platelet-bound /sup 3/H paf-acether displacement of 28.3 +/- 6.3%, 31.1 +/- 4.0% and 26.7 +/- 5.6% was observed using 50 nM unlabelled paf-acether, 60 ..mu..M BN 52021 or both substances together (vs 4.3 +/- 7.2% for vehicle alone). No degradation of /sup 3/H paf-acether occurred as assessed by high pressure liquid chromatography. These results demonstrate that BN 52021 competes directly with paf-acether binding sites on human platelets.« less

New polymeric precursors to SiNCB, BN, and La(3)Ni(2)B(2)N(3) materials

NASA Astrophysics Data System (ADS)

Wideman, Thomas W.

Boron-containing non-oxide ceramics demonstrate a number of important structural, electronic and physical properties. However, the lack of general synthetic routes to generate these materials with controlled composition, under moderate conditions, and in processed forms, has hampered both scientific studies and practical applications. The goal of the work described in this dissertation was to develop efficient new polymeric precursor routes to boron-containing materials including SiNCB ceramics composites, boron nitride fibers, and quaternary metal boro-nitride superconductors. Two types of polyborosilazane precursors to SiNCB ceramics were developed. Borazine-co-silazane copolymers were prepared through the thermal copolymerization of borazine with two silazanes, tris(trimethylsilylamino)silane, and 1,1,3,3,5,5 -hexamethylcyclotrisilazane. Polyborosilazanes with pendent boron-containing species were obtained by the modification of preformed hydridopolysilazane polymers with three monofunctional boranes: pinacolborane, 2,4-diethylborazine and 1,3-dimethyl-1,3-diaza-2-boracyclopentane. Pyrolyses of both types of polyborosilazanes produced SiNCB ceramics with controllable boron contents, enhanced thermal stabilities, and reduced crystallinity. Processible polymeric precursors to BN were also achieved by the chemical modification of polyborazylene, (Bsb3Nsb3Hsb{˜ 4}rbrack sb{x}, with diethylamine, dipentylamine, and hexamethyldisilazane. The modified polymers, unlike the parent polyborazylene, do not crosslink at low temperatures, and therefore proved to be ideal melt-spinnable precursors to BN ceramic fibers. A new polymeric precursor route to the recently discovered Lasb3Nisb2Bsb2Nsb3 superconductor (Tc = 12K) was developed by reacting lanthanum and nickel powders dispersed in the polyborazylene, to produce the intermetallic in excellent yields. The use of the polymer as a "reagent" provided a controllable, solid state source of nitrogen, and allows for the large

An incidentally found inflamed uterine myoma causing low abdominal pain, using Tc-99m-tektrotyd single photon emission computed tomography-CT hybrid imaging.

PubMed

Zandieh, Shahin; Schütz, Matthias; Bernt, Reinhard; Zwerina, Jochen; Haller, Joerg

2013-01-01

We report the case of a 50-year-old woman presented with a history of right hemicolectomy due to an ileocecal neuroendocrine tumor and left breast metastasis. Owing to a slightly elevated chromogranin A-level and lower abdominal pain, single photon emission computed tomography-computer tomography (SPECT-CT) was performed. There were no signs of recurrence on the SPECT-CT scan, but the patient was incidentally found to have an inflamed intramural myoma. We believe that the slightly elevated chromogranin A-level was caused by the hypertension that the patient presented. In the clinical context, this is a report of an inflamed uterine myoma seen as a false positive result detected by TC-99m-Tc-EDDA/HYNIC-Tyr3-Octreotide (Tektrotyd) SPECT-CT hybrid imaging.

The duality of LysU, a catalyst for both Ap4A and Ap3A formation.

PubMed

Wright, Michael; Boonyalai, Nonlawat; Tanner, Julian A; Hindley, Alison D; Miller, Andrew D

2006-08-01

Heat shock inducible lysyl-tRNA synthetase of Escherichia coli (LysU) is known to be a highly efficient diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) synthase. However, we use an ion-exchange HPLC technique to demonstrate that active LysU mixtures actually have a dual catalytic activity, initially producing Ap4A from ATP, before converting that tetraphosphate to a triphosphate. LysU appears to be an effective diadenosine 5',5'''-P1,P3-triphosphate (Ap3A) synthase. Mechanistic investigations reveal that Ap3A formation requires: (a) that the second step of Ap4A formation is slightly reversible, thereby leading to a modest reappearance of adenylate intermediate; and (b) that phosphate is present to trap the intermediate (either as inorganic phosphate, as added ADP, or as ADP generated in situ from inorganic phosphate). Ap3A forms readily from Ap4A in the presence of such phosphate-based adenylate traps (via a 'reverse-trap' mechanism). LysU is also clearly demonstrated to exist in a phosphorylated state that is more physically robust as a catalyst of Ap4A formation than the nonphosphorylated state. However, phosphorylated LysU shows only marginally improved catalytic efficiency. We note that Ap3A effects have barely been studied in prokaryotic organisms. By contrast, there is a body of literature that describes Ap3A and Ap4A having substantially different functions in eukaryotic cells. Our data suggest that Ap3A and Ap4A biosynthesis could be linked together through a single prokaryotic dual 'synthase' enzyme. Therefore, in our view there is a need for new research into the effects and impact of Ap3A alone and the intracellular [Ap3A]/[Ap4A] ratio on prokaryotic organisms.

Additional lesions detected in therapeutic scans with 177Lu-DOTATATE reflect higher affinity of 177Lu-DOTATATE for somatostatin receptors.

PubMed

Mirzaei, Siroos; Bastati, Brigitte; Lipp, Rainer W; Knoll, Peter; Zojer, Niklas; Ludwig, Heinz

2011-01-01

Peptide receptor-targeted radionuclide therapy (PRRT) of somatostatin receptor (SR)-expressing neuroendocrine tumors (NETs) has become an established therapeutic option in patients with advanced NETs. The aim of this study was to compare the lesion detection rate of (99m)Tc-EDDA/HYNIC-TOC, a newly developed tracer for NET imaging, with (177)Lu-DOTATATE used for PRRT. 8 patients (4 women, 4 men, age range 46-76 years) with histologically proven NETs, who showed high SR loads by (99m)Tc-EDDA/HYNIC-TOC scintigraphy, were treated with (177)Lu-DOTATATE. After treatment, all patients were subjected to whole-body scintigraphy with additional low-dose single-photon emission computed tomography (SPECT-CT) of the chest and abdomen. All patients demonstrated (177)Lu-DOTATATE accumulation in all lesions previously detected by (99m)Tc- EDDA/HYNIC-TOC scintigraphy. Three patients showed additional lesions in the liver and lungs. SPECT-CT after (177)Lu-DOTATATE therapy may be helpful in detecting additional lesions not seen using (99m)Tc-EDDA/HYNIC-TOC. This could reflect the broader affinity of (177)Lu-DOTATATE for SRs compared with (99m)Tc-EDDA/HYNIC-TOC. Copyright © 2011 S. Karger AG, Basel.

Tribological properties of epoxy composite coatings reinforced with functionalized C-BN and H-BN nanofillers

NASA Astrophysics Data System (ADS)

Yu, Jingjing; Zhao, Wenjie; Wu, Yinghao; Wang, Deliang; Feng, Ruotao

2018-03-01

A series of epoxy resin (EP) composite coatings reinforced with functionalized cubic boron nitride (FC-BN) and functionalized hexagonal boron nitride (FH-BN) were fabricated successfully on 316L stainless steel by hand lay-up technique. The structure properties were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). The morphologies were characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Moreover, UMT-3 tribometer and surface profiler were used to investigate tribological behaviors of as-prepared composite coatings under dry friction and seawater conditions respectively. The results demonstrated that the presence of FC-BN or FH-BN fillers could greatly decrease the friction coefficient (COF) and wear rate of epoxy, in addition, composite coatings possess better tribological properties under seawater condition which was attributed to the lubricating effect of seawater. Moreover, FC-BN endows the composite coatings the highest wear resistance, and FH-BN /EP composite coatings exhibited the best friction reduction performance which is attributed to the self-lubricating performance of lamella structure for FH-BN sheet.

99mTc-D(LPR): A novel retro-inverso peptide for VEGF receptor-1 targeted tumor imaging.

PubMed

Rezazadeh, Farzaneh; Sadeghzadeh, Nourollah; Abedi, Seyed Mohammad; Abediankenari, Saeid

2018-05-31

The aim of this study was to evaluate the ability of D (LPR), a novel retro-inverso peptidomimetic derivative for imaging colon cancer. Two different D (LPR) analogs were designed and compared based on conjugation of HYNIC at peptide's C or N terminal and then labeled with technetium-99m using tricine/EDDA as an exchange coligands. The radiolabeled conjugates were assessed for in vitro stability in saline and serum. The VEGFR-1 and NRP-1 receptors affinity, in vitro internalization and also dissociation Constance was evaluated. SPCET imaging and biodistribution studies were performed in nude mice bearing HT-29 xenograft tumors. Both peptides labeled with technetium-99m in high radiochemical yield (˃97%). Peptide stability studies indicated a high metabolic stability of the radiopeptides in solution and serum. In vitro blocking studies demonstrated specific binding and internalization of [ 99m Tc]Tc-HYNIC-peptides in cultured HUVEC cells. The K d value for 99m Tc-peptide 1 and 99m Tc-peptide 2 were found to be 56.8 ± 12.9 nM and 71.6 ± 17.9 nM respectively. The tumor to muscle ratio was significant at 0.5 and 1 h after injection (4.5 and 4 for 99m Tc-peptide 1 and 4.9 and 4.4 for 99m Tc-peptide 2 at 0.5 and 1 h p.i. respectively). SPECT imaging studies revealed that both radioconjugates had prominent activity accumulation in VEGFR-1 and NRP-1 expressing HT-29 tumors. This study is the first instance of using a radiolabeled retro-inverso peptide for tumor imaging which is a promising tool to improve the performance of fragile peptide probes in vivo as imaging agents and warrant further investigations in other peptide-target systems. Copyright © 2018 Elsevier Inc. All rights reserved.

78 FR 64894 - Airworthiness Directives; B-N Group Ltd. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-30

... requires a one-time inspection and functional test of the engine control cables and, depending on findings... Airworthiness Directives; B-N Group Ltd. Airplanes AGENCY: Federal Aviation Administration (FAA), Department of... airworthiness directive (AD) for B-N Group Ltd. Models BN-2, BN-2A, BN-2A-2, BN-2A-3, BN-2A-6, BN-2A-8, BN- 2A-9...

78 FR 21072 - Airworthiness Directives; B-N Group Ltd. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-09

... Airworthiness Directives; B-N Group Ltd. Airplanes AGENCY: Federal Aviation Administration (FAA), Department of... airworthiness directive (AD) for B-N Group Ltd. Models BN-2, BN-2A, BN2A MK. III, BN2A MK. III-2, BN2A MK. III-3... further information by examining the MCAI in the AD docket. Relevant Service Information B-N Group Limited...

Identification and characterization of LysM effectors in Penicillium expansum.

PubMed

Levin, Elena; Ballester, Ana Rosa; Raphael, Ginat; Feigenberg, Oleg; Liu, Yongsheng; Norelli, John; Gonzalez-Candelas, Luis; Ma, Jing; Dardick, Christopher; Wisniewski, Michael; Droby, Samir

2017-01-01

P. expansum is regarded as one of the most important postharvest rots of apple fruit and is also of great concern to fruit processing industries. Elucidating the pathogenicity mechanism of this pathogen is of utmost importance for the development of effective and safe management strategies. Although, many studies on modification of the host environment by the pathogen were done, its interactions with fruit during the early stages of infection and the virulence factors that mediate pathogenicity have not been fully defined. Effectors carrying LysM domain have been identified in numerous pathogenic fungi and their role in the first stages of infection has been established. In this study, we identified 18 LysM genes in the P. expansum genome. Amino acid sequence analysis indicated that P. expansum LysM proteins belong to a clade of fungal-specific LysM. Eleven of the discovered LysM genes were found to have secretory pathway signal peptide, among them, 4 (PeLysM1 PeLysM2, PeLysM3 and PeLysM4) were found to be highly expressed during the infection and development of decay of apple fruit. Effect of targeted deletion of the four putative PeLysM effectors on the growth and pathogenicity was studied. Possible interactions of PeLysM with host proteins was investigated using the yeast-two-hybrid system.

Tc-99m Glu-Cys-Gly-His-Gly-Lys (ECG-HGK), a novel Tc-99m labeled hexapeptide for molecular tumor imaging.

PubMed

Kim, Dae-Weung; Kim, Myoung Hyoun; Kim, Chang Guhn

2016-03-01

Domain 5 of kinin-free high molecular weight kininogen inhibits the adhesion of many tumor cell lines, and it has been reported that the histidine-glycine-lysine (HGK)-rich region might be responsible for inhibition of cell adhesion. The authors developed HGK-containing hexapeptide, glutamic acid-cysteine-glycine (ECG)-HGK, and evaluated the utility of Tc-99m ECG-HGK for tumor imaging. Hexapeptide, ECG-HGK was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling efficiency was evaluated. The uptake of Tc-99m ECG-HGK within HT-1080 cells was evaluated in vitro. In HT-1080 tumor-bearing mice, gamma imaging and biodistribution studies were performed. The complexes Tc-99m ECG-HGK was prepared in high yield. The uptake of Tc-99m ECG-HGK within the HT-1080 tumor cells had been demonstrated by in vitro studies. The gamma camera imaging in the murine model showed that Tc-99m ECG-HGK was accumulated substantially in the HT-1080 tumor (tumor-to-muscle ratio = 5.7 ± 1.4 at 4 h), and the tumoral uptake was blocked by the co-injection of excess HGK (tumor-to-muscle ratio = 2.8 ± 0.6 at 4 h). In the present study, Tc-99m ECG-HGK was developed as a new tumor imaging agents. Our in vitro and in vivo studies revealed specific function of Tc-99m ECG-HGK for tumor imaging. Copyright © 2016 John Wiley & Sons, Ltd.

Short communication: Semiquantitative assessment of 99mTc-EDDA/HYNIC-TOC scintigraphy in differentiation of solitary pulmonary nodules--a complementary role to visual analysis.

PubMed

Płachcińska, Anna; Mikołajczak, Renata; Kozak, Józef; Rzeszutek, Katarzyna; Kuśmierek, Jacek

2006-02-01

The aim of this study was the assessment of a value of a semiquantitative analysis of scintigrams obtained with (99m)Tc-EDDA/HYNIC-TOC as a radiopharmaceutical (RPH) in differential diagnosis of solitary pulmonary nodules (SPNs), as a method complementary to visual evaluation of scintigrams. Scintigraphic images of 59 patients (33 males and 26 females between 34 and 78 years of age, mean value, 57) with SPN on chest radiographs (39 malignant and 20 benign) were retrospectively assessed semiquantitatively. Visual scintigram analysis was made earlier, prospectively. Nodule diameters ranged from 1 to 4 (mean 2.2) cm. A single photon emission computed tomography (SPECT) acquisition was performed at 2-4 hours after administration of 740 to 925 MBq of a RPH. Verification of scintigraphic results was based on a pathological examination of tumor samples (histopathology or cytology) and, in some cases, on bacteriological studies. As an additional criterion for tumor benignity, its stable size in a time interval not shorter than 3 years was accepted. A simple, semiquantitative method for assessment of radiopharmaceutical uptake in SPNs was used, based on "count sample" taken from tumor center (T) in relation to radiopharmaceutical concentration in the background (B) measured in the contralateral lung. A criterion for optimal differentiation between malignant and benign nodules (T/B ratio threshold value) was introduced, based on a receiver operating characteristic (ROC) curve. Additionally, a value of T/B ratio was searched for, excluding tumor benignity with high probability. Visual analysis of scintigrams revealed enhanced uptake of RPH at 36 of 39 (92%) sites, corresponding to locations of malignant nodules (including 34 of 35-97% cases of lung cancer). In 13 of 20 (65%) benign nodules, true negative results were obtained. Accuracy of the method equalled 83%. Optimal differentiation between malignant and benign nodules was found for a value of a T/B ratio amounting to 2

Surface-enhanced Raman difference between bombesin and its modified analogues on the colloidal and electrochemically roughen silver surfaces.

PubMed

Podstawka, Edyta; Ozaki, Yukihiro

2008-10-01

In this article, surface-enhanced Raman scattering (SERS) spectra of bombesin (BN) and its six modified analogues ([D-Phe(12)]BN, [Tyr(4)]BN, [Tyr(4),D-Phe(12)]BN, [D-Phe(12),Leu(14)]BN, [Leu(13)-(R)-Leu(14)]BN, and [Lys(3)]BN) on a colloidal silver surface are reported and compared with SERS spectra of these species immobilized onto an ellectrochemically roughen silver electrode. Changes in enhancement and wavenumber of proper bands upon adsorption on different silver surfaces are consistent with BN and its analogues adsorption primarily through Trp(8). Slightly different adsorption states of these molecules are observed depending upon natural amino acids substitution. For example, the indole ring in all the peptides interacts with silver nanoparticles in a edge-on orientation. It is additionally coordinated to the silver through the N(1)--H bond for all the peptides, except [Phe(12)]BN. This is in contrary to the results obtained for the silver roughen electrode that show direct but not strong N(1)--H/Ag interaction for all peptides except [D-Phe(12),Leu(14)]BN and [Leu(13)-(R)-Leu(14)]BN. For BN only C==O is not involved in the chemical coordination with the colloidal surface. [Lys(3)]BN and BN also adsorb with the C--N bond of NH(2) group normal and horizontal, respectively, to the colloidal surface, whereas C--NH(2) in other peptides is tilted to this surface. Also, the Trp(8) --CH(2)-- moiety of only [Tyr(4)]BN, [Lys(3)]BN, and [Tyr(4),D-Phe(12)]BN coordinates to Ag, whereas the Phe(12) ring of [Phe(12)]BN, [Tyr(4),D-Phe(12)]BN, and [D-Phe(12),Leu(14)]BN assists in the peptides binding only on the colloidal silver. (c) 2008 Wiley Periodicals, Inc.

Quasi-Two-Dimensional h-BN/β-Ga2O3 Heterostructure Metal-Insulator-Semiconductor Field-Effect Transistor.

PubMed

Kim, Janghyuk; Mastro, Michael A; Tadjer, Marko J; Kim, Jihyun

2017-06-28

β-gallium oxide (β-Ga 2 O 3 ) and hexagonal boron nitride (h-BN) heterostructure-based quasi-two-dimensional metal-insulator-semiconductor field-effect transistors (MISFETs) were demonstrated by integrating mechanical exfoliation of (quasi)-two-dimensional materials with a dry transfer process, wherein nanothin flakes of β-Ga 2 O 3 and h-BN were utilized as the channel and gate dielectric, respectively, of the MISFET. The h-BN dielectric, which has an extraordinarily flat and clean surface, provides a minimal density of charged impurities on the interface between β-Ga 2 O 3 and h-BN, resulting in superior device performances (maximum transconductance, on/off ratio, subthreshold swing, and threshold voltage) compared to those of the conventional back-gated configurations. Also, double-gating of the fabricated device was demonstrated by biasing both top and bottom gates, achieving the modulation of the threshold voltage. This heterostructured wide-band-gap nanodevice shows a new route toward stable and high-power nanoelectronic devices.

49 CFR 178.39 - Specification 3BN seamless nickel cylinders.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Type, size and service pressure. A DOT 3BN cylinder is a seamless nickel cylinder with a water capacity (nominal) not over 125 pounds water capacity (nominal) and a service pressure at least 150 to not over 500...) Wall thickness. The wall stress may not exceed 15,000 psi. A minimum wall thickness of 0.100 inch is...

49 CFR 178.39 - Specification 3BN seamless nickel cylinders.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Type, size and service pressure. A DOT 3BN cylinder is a seamless nickel cylinder with a water capacity (nominal) not over 125 pounds water capacity (nominal) and a service pressure at least 150 to not over 500...) Wall thickness. The wall stress may not exceed 15,000 psi. A minimum wall thickness of 0.100 inch is...

Comparative in vivo evaluation of two novel 99mTc labelled bombesin derivatives

NASA Astrophysics Data System (ADS)

Gourni, Eleni; Bouziotis, Penelope; Zikos, Christos; Loudos, George; Xanthopoulos, Stavros; Fani, Melpomeni; Archimandritis, Spyridon C.; Varvarigou, Alexandra D.

2006-12-01

Bombesin (BN), a 14 amino acid peptide, is an analogue of human gastrin-releasing-peptide (GRP) that binds to GRP receptors (GRP-R) with high affinity and specificity. In addition to this physiological role, GRP, through its interaction with GRP-R, promotes tumour growth in a number of human cancer cell lines. The GRP receptors are over-expressed on a variety of human cancer cells. Aim of the present work is the study of two novels BN-like peptides, by investigating the radiochemical and radiopharmacological behaviour of their complexes with metals. The derivatives under study are: Gly-Gly-Cys-Aca-BN [2-14] where Aca: 6-amino-hexanoic acid. Pyroglutamic acid in the bombesin molecule has been replaced by the chemical group Gly-Gly-Cys-Aca, which bears an amino-acid combination capable of complexing a variety of radiometals. The other derivative under study is: Gly-Gly-Cys-Aca-BN [7-14]. This moiety of the peptide has been chosen because it has been proven to be a potent GRP agonist. The peptide derivatives were synthesized by SPPS, according to the Fmoc strategy and were identified by reverse phase high performance liquid chromatography (RP-HPLC). Radiolabelling with 99mTc was performed via the precursor 99mTc-gluconate. The stability of the radiolabelled species was examined with time. In vivo studies of the two 99mTc-labelled derivatives were performed, comparatively, in normal mice, attention being focused on GRP receptor-bearing organs, and in experimentally induced prostate cancer models. Experimental tumours were imaged in a small field-of-view animal gamma camera.

Thermal Shock Resistance of Si3N4/h -BN Composites Prepared via Catalytic Reaction-Bonding Route

NASA Astrophysics Data System (ADS)

Yang, Wanli; Peng, Zhigang; Dai, Lina; Shi, Zhongqi; Jin, Zhihao

2017-09-01

Si3N4/h-BN ceramic matrix composites were prepared via a catalytic reaction-bonding route by using ZrO2 as nitridation catalyst, and the water quenching (fast cooling) and molten aluminum quenching tests (fast heating) were carried out to evaluate the thermal shock resistance of the composites. The results showed that the thermal shock resistance was improved obviously with the increase in h-BN content, and the critical thermal shock temperature difference (Δ T c) reaches as high as 780 °C when the h-BN content was 30 wt.%. The improvement of thermal shock resistance of the composites was mainly due to the crack tending to quasi static propagating at weak bonding interface between Si3N4 and h-BN with the increase in h-BN content. For the molten aluminum quenching test, the residual strength showed no obvious decrease compared with water quenching test, which could be caused by the mild stress condition on the surface. In addition, a calculated parameter, volumetric crack density ( N f), was presented to quantitative evaluating the thermal shock resistance of the composites in contrast to the conventional R parameter.

Anisotropic Effective Mass, Optical Property, and Enhanced Band Gap in BN/Phosphorene/BN Heterostructures.

PubMed

Hu, Tao; Hong, Jisang

2015-10-28

Phosphorene is receiving great research interests because of its peculiar physical properties. Nonetheless, the phosphorus has a trouble of degradation due to oxidation. Hereby, we propose that the electrical and optical anisotropic properties can be preserved by encapsulating into hexagonal boron nitride (h-BN). We found that the h-BN contributed to enhancing the band gap of the phosphorene layer. Comparing the band gap of the pristine phosphorene layer, the band gap of the phosphorene/BN(1ML) system was enhanced by 0.15 eV. It was further enhanced by 0.31 eV in the BN(1ML)/phosphorene/BN(1ML) trilayer structure. However, the band gap was not further enhanced when we increased the thickness of the h-BN layers even up to 4 MLs. Interestingly, the anisotropic effective mass and optical property were still preserved in BN/phosphorene/BN heterostructures. Overall, we predict that the capping of phosphorene by the h-BN layers can be an excellent solution to protect the intrinsic properties of the phosphorene.

High hardness BaCb-(BxOy/BN) composites with 3D mesh-like fine grain-boundary structure by reactive spark plasma sintering.

PubMed

Vasylkiv, Oleg; Borodianska, Hanna; Badica, Petre; Grasso, Salvatore; Sakka, Yoshio; Tok, Alfred; Su, Liap Tat; Bosman, Michael; Ma, Jan

2012-02-01

Boron carbide B4C powders were subject to reactive spark plasma sintering (also known as field assisted sintering, pulsed current sintering or plasma assisted sintering) under nitrogen atmosphere. For an optimum hexagonal BN (h-BN) content estimated from X-ray diffraction measurements at approximately 0.4 wt%, the as-prepared BaCb-(BxOy/BN) ceramic shows values of Berkovich and Vickers hardness of 56.7 +/- 3.1 GPa and 39.3 +/- 7.6 GPa, respectively. These values are higher than for the vacuum SPS processed B4C pristine sample and the h-BN -mechanically-added samples. XRD and electronic microscopy data suggest that in the samples produced by reactive SPS in N2 atmosphere, and containing an estimated amount of 0.3-1.5% h-BN, the crystallite size of the boron carbide grains is decreasing with the increasing amount of N2, while for the newly formed lamellar h-BN the crystallite size is almost constant (approximately 30-50 nm). BN is located at the grain boundaries between the boron carbide grains and it is wrapped and intercalated by a thin layer of boron oxide. BxOy/BN forms a fine and continuous 3D mesh-like structure that is a possible reason for good mechanical properties.

Hb taradale [beta82(EF6)Lys-->Arg]: a novel mutation at a 2,3-diphosphoglycerate binding site.

PubMed

Brennan, Stephen O; Sheen, Campbell; Chan, Tim; George, Peter M

2005-01-01

Hb Taradale [beta82(EF6)Lys-->Arg] was initially detected as a split Hb A0 peak on Hb A1c, monitoring. Red cell parameters, hemoglobin (Hb) electrophoresis and stability tests were normal. Mass spectrometry (ms) clearly identified a variant beta chain with a mass increase of 28 Da and peptide mapping located the mutation site to peptide betaT-9. DNA sequencing confirmed the presence of a novel beta82(EF6)Lys-->Arg mutation. This conservative substitution at a 2,3-diphosphoglycerate (2,3-DPG) binding site did not, however, appear to affect the P50 for oxygen binding.

Structure and luminescence properties of 10-BN sheets

NASA Astrophysics Data System (ADS)

Han, Wei-Qiang; Liu, Lijia; Sham, T. K.; Liu, Zhenxian

2012-10-01

Isotopic 10BN sheets were first prepared using graphene sheets as templates to react with 10B2O3. The edge-areas of BN sheets have much higher oxygen-doping ratios compared to other areas. The emission peak of X-ray excited optical luminescence spectra of the 10BN-sheets is broader and red-shifted because of the isotopic effect. A broad violet-blue emission at a wavelength centered at ~400 nm is assigned to the defect emission due to oxygen-doping and defects in the BN network.

Somatostatin receptor scintigraphy in patients with rheumatoid arthritis and secondary Sjögren's syndrome treated with Infliximab: a pilot study.

PubMed

Anzola-Fuentes, L K; Chianelli, M; Galli, F; Glaudemans, A W J M; Martin Martin, L; Todino, V; Migliore, A; Signore, A

2016-12-01

Human T lymphocytes infiltrating tissues in autoimmune diseases are known to express somatostatin receptors amongst other activation markers. In this study, we evaluated whether somatostatin receptor scintigraphy (SRS) using a radiolabelled somatostatin analogue ((99m)Tc-EDDA/tricine-HYNIC-tyr(3)-octreotide ((99m)Tc-EDDA/HYNIC-TOC)) is able to detect the presence of immune-mediated processes in patients with rheumatoid arthritis and secondary Sjögren's syndrome. We also aimed to evaluate whether positivity to SRS was predictive of therapeutic response and if SRS could be used for monitoring the efficacy of immunomodulatory treatment. Eighteen patients with rheumatoid arthritis and secondary Sjögren's syndrome not responding to conventional treatment were recruited for treatment with infliximab, a monoclonal antibody against TNF-α. All patients had complete blood cell count, renal and liver function tests, measurements of ESR, CRP, ANA, ENA, and anti-dsDNA antibodies, functional salivary gland scintigraphy, labial biopsy, and ophthalmologic assessment with Schirmer's test and tear film break-up time (BUT). Diagnosis was made according to the revised criteria of the American-European Consensus Group. All patients underwent SRS at baseline and after 3-6 months of therapy with infliximab. Eleven out of 18 had repeat SRS images. Images of the salivary glands and major joints were acquired 3 h after injection of 370 MBq of (99m)Tc-EDDA/HYNIC-TOC. Image analysis was performed semi-quantitatively. All patients showed uptake of (99m)Tc-EDDA/HYNIC-TOC in the joints. Salivary glands also showed variable radiopharmaceutical uptake in 12 out of 18 patients, but all patients showed presence of lymphocytic infiltration at labial salivary gland biopsy. All patients, who repeated the study after treatment, showed significant reduction of somatostatin uptake in the joints but not in the salivary glands. SRS using (99m)Tc-EDDA/HYNIC-TOC may be a useful imaging tool to assess

(Fuzzy) Ideals of BN-Algebras

PubMed Central

Walendziak, Andrzej

2015-01-01

The notions of an ideal and a fuzzy ideal in BN-algebras are introduced. The properties and characterizations of them are investigated. The concepts of normal ideals and normal congruences of a BN-algebra are also studied, the properties of them are displayed, and a one-to-one correspondence between them is presented. Conditions for a fuzzy set to be a fuzzy ideal are given. The relationships between ideals and fuzzy ideals of a BN-algebra are established. The homomorphic properties of fuzzy ideals of a BN-algebra are provided. Finally, characterizations of Noetherian BN-algebras and Artinian BN-algebras via fuzzy ideals are obtained. PMID:26125050

Diamond- cBN alloy: A universal cutting material

DOE PAGES

Wang, Pei; He, Duanwei; Wang, Liping; ...

2015-09-08

Diamond and cubic boron nitride ( cBN) as conventional superhard materials have found widespread industrial applications, but both have inherent limitations. Diamond is not suitable for high-speed cutting of ferrous materials due to its poor chemical inertness, while cBN is only about half as hard as diamond. Because of their affinity in structural lattices and covalent bonding character, diamond and cBN could form alloys that can potentially fill the performance gap. However, the idea has never been demonstrated because samples obtained in the previous studies were too small to be tested for their practical performance. Here, we report the synthesismore » and characterization of transparent bulk diamond- cBN alloy compacts whose diameters (3 mm) are sufficiently large for them to be processed into cutting tools. The testing results show that the diamond- cBN alloy has superior chemical inertness over polycrystalline diamond and higher hardness than single crystal cBN. In conclusion, high-speed cutting tests on hardened steel and granite suggest that diamond- cBN alloy is indeed a universal cutting material.« less

Diamond-cBN alloy: A universal cutting material

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Pei; High Pressure Science and Engineering Center and Department of Physics and Astronomy, University of Nevada Las Vegas, Las Vegas, Nevada 89154; He, Duanwei, E-mail: duanweihe@scu.edu.cn

Diamond and cubic boron nitride (cBN) as conventional superhard materials have found widespread industrial applications, but both have inherent limitations. Diamond is not suitable for high-speed cutting of ferrous materials due to its poor chemical inertness, while cBN is only about half as hard as diamond. Because of their affinity in structural lattices and covalent bonding character, diamond and cBN could form alloys that can potentially fill the performance gap. However, the idea has never been demonstrated because samples obtained in the previous studies were too small to be tested for their practical performance. Here, we report the synthesis andmore » characterization of transparent bulk diamond-cBN alloy compacts whose diameters (3 mm) are sufficiently large for them to be processed into cutting tools. The testing results show that the diamond-cBN alloy has superior chemical inertness over polycrystalline diamond and higher hardness than single crystal cBN. High-speed cutting tests on hardened steel and granite suggest that diamond-cBN alloy is indeed a universal cutting material.« less

Diamond- cBN alloy: A universal cutting material

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Pei; He, Duanwei; Wang, Liping

Diamond and cubic boron nitride ( cBN) as conventional superhard materials have found widespread industrial applications, but both have inherent limitations. Diamond is not suitable for high-speed cutting of ferrous materials due to its poor chemical inertness, while cBN is only about half as hard as diamond. Because of their affinity in structural lattices and covalent bonding character, diamond and cBN could form alloys that can potentially fill the performance gap. However, the idea has never been demonstrated because samples obtained in the previous studies were too small to be tested for their practical performance. Here, we report the synthesismore » and characterization of transparent bulk diamond- cBN alloy compacts whose diameters (3 mm) are sufficiently large for them to be processed into cutting tools. The testing results show that the diamond- cBN alloy has superior chemical inertness over polycrystalline diamond and higher hardness than single crystal cBN. In conclusion, high-speed cutting tests on hardened steel and granite suggest that diamond- cBN alloy is indeed a universal cutting material.« less

Fundamental Discovery of New Phases and Direct Conversion of Carbon into Diamond and hBN into cBN and Properties

NASA Astrophysics Data System (ADS)

Narayan, Jagdish; Bhaumik, Anagh

2016-04-01

pulsed laser evaporation of carbon and obtained cBN/diamond composites, where cBN acts as template for diamond growth. Both diamond and cBN grown from super undercooled liquid can be alloyed with both p- and n-type dopants. This process allows carbon to diamond and hBN to cBN conversions and formation of useful nanostructures and microstructures at ambient temperatures in air at atmospheric pressure on practical and heat-sensitive substrates in a controlled way without need for any catalysts and hydrogen to stabilize sp3 bonding for diamond and cBN phases.

DFT STUDY OF CO AND NO ADSORPTION ON BORON NITRIDE (BN)n = 3 - 5 NANOCLUSTERS

NASA Astrophysics Data System (ADS)

Zahedi, Ehsan; Pangh, Abdolhakim; Ghorbanpour, Hamed

2015-11-01

Interaction of CO and NO molecules by different orientations on (BN)n=3-5 clusters have been studied at the B3LYP/6-311+G* level of theory. Total electronic energies have been corrected for geometrical counterpoise (gCP) and dispersion (D3) energies at the B3LYP/6-31G* level. Formation of a new sigma bond between the gas and (BN)3 cluster, atom in molecules (AIM) results, density of states spectrums (DOS), molecular electrostatic potential (MEP) surfaces, and visualization of wave function of molecular orbitals in the nearest bonding regions to the Fermi level have confirmed that adsorption of CO by carbon end atom, and NO by nitrogen end atom is covalent in nature, so that the charge transfer is occurred from gas molecule to the cluster.

Site-specific crosslinking of 4-thiouridine-modified human tRNA(3Lys) to reverse transcriptase from human immunodeficiency virus type I.

PubMed Central

Mishima, Y; Steitz, J A

1995-01-01

We have mapped specific RNA-protein contacts between human immunodeficiency virus (HIV) type I reverse transcriptase (RT) and its natural primer, human tRNA(3Lys), using a site-specific crosslinking strategy. Four different tRNA(3Lys) constructs with a single 32P-labeled 4-thiouridine (4-thioU) residue at positions -1, 16, 36 or 41 were synthesized. After incubation with RT followed by irradiation, crosslinks were localized to either the p66 or p51 subunit of RT by digestion with nuclease and SDS gel fractionation. 4-thioU at position -1 or 16 transferred label to the p66 subunit almost exclusively (> 90%), whereas position 36 labeled both p66 and p51 (3:1). Position 41 yielded no detectable crosslinks. The region of p66 contacted by position -1 of tRNA(3Lys) was localized to the 203 C-terminal amino acids of RT by CNBr cleavage, whereas a 127 amino acid-CNBr peptide (residues 230-357) from both p66 and p51 was labeled by position 36. Functionality of the 4-thioU-modified tRNA(3Lys)(-1) crosslinked to RT in the presence of an RNA but not a DNA template was demonstrated by the ability of the tRNA to be extended. These results localize the 5' half of the tRNA on the interface between the two RT subunits, closer to the RNase H domain than to the polymerase active site, in accord with previous suggestions. They argue further that a specific binding site for the 5' end of the primer tRNA(3Lys) may exist within the C-terminal portion of the p66 subunit, which could be important for the initiation of reverse transcription. Images PMID:7540137

Electrophoretic Deposition of Chitosan/h-BN and Chitosan/h-BN/TiO₂ Composite Coatings on Stainless Steel (316L) Substrates.

PubMed

Raddaha, Namir S; Cordero-Arias, Luis; Cabanas-Polo, Sandra; Virtanen, Sannakaisa; Roether, Judith A; Boccaccini, Aldo R

2014-03-04

This article presents the results of an experimental investigation designed to deposit chitosan/hexagonal boron nitride (h-BN) and chitosan/h-BN/titania (TiO₂) composites on SS316L substrates using electrophoretic deposition (EPD) for potential antibacterial applications. The influence of EPD parameters (voltage and deposition time) and relative concentrations of chitosan, h-BN and TiO₂ in suspension on deposition yield was studied. The composition and structure of deposited coatings were investigated by FTIR, XRD and SEM. It was observed that h-BN and TiO₂ particles were dispersed in the chitosan matrix through simultaneous deposition. The adhesion between the electrophoretic coatings and the stainless steel substrates was tested by using tape test technique, and the results showed that the adhesion strength corresponded to 3B and 4B classes. Corrosion resistance was evaluated by electrochemical polarization curves, indicating enhanced corrosion resistance of the chitosan/h-BN/TiO₂ and chitosan/h-BN coatings compared to the bare stainless steel substrate. In order to investigate the in-vitro inorganic bioactivity, coatings were immersed in simulated body fluid (SBF) for 28 days. FTIR and XRD results showed no formation of hydroxyapatite on the surface of chitosan/h-BN/TiO₂ and chitosan/h-BN coatings, which are therefore non bioactive but potentially useful as antibacterial coatings.

Reaction paths in the system Al 2O 3-hBN-Y

NASA Astrophysics Data System (ADS)

Reichert, K.; Oreshina, O.; Cremer, R.; Neuschütz, D.

2001-07-01

As part of the investigations on the suitability of a new concept for a tailored fiber-matrix interface in sapphire fiber reinforced NiAl matrix composites for application as a high-temperature structural material, the interfacial reactions in the system alumina-hexagonal boron nitride-yttrium (Al 2O 3-hBN-Y) have been examined in the temperature range of 1100-1300°C. For this, alumina substrates were coated with hBN by means of CVD and subsequently with sputter deposited yttrium. Afterwards the samples were annealed for up to 16 h under inert atmosphere. Grazing incidence X-ray diffraction (GIXRD) served to analyze the phases formed by diffusion processes in the reaction zone. The peak intensities in these diffraction patterns were used to evaluate the sequence of phases formed due to diffusion and reaction. After the initial formation of YN and YB 2, the phases Y 2O 3, Al 2Y, and YB 4 were observed. Even longer annealing times or higher temperatures, respectively, led to the formation of the ternary oxides YAlO 3 and Y 3Al 5O 12 as well as metallic aluminum.

Synthesis and Characterization of Quenched and Crystalline Phases: Q-Carbon, Q-BN, Diamond and Phase-Pure c-BN

NASA Astrophysics Data System (ADS)

Bhaumik, Anagh; Narayan, Jagdish

2018-04-01

We report the synthesis and characterization of quenched (Q-carbon and Q-BN) and crystalline (diamond and c-BN) phases using a non-equilibrium technique. These phases are formed as a result of the melting and subsequent quenching of amorphous carbon and nanocrystalline h-BN in a super undercooled state by using high-power nanosecond laser pulses. Pulsed laser annealing also leads to the formation of nanoneedles, microneedles and single-crystal thin films of diamond and c-BN. This formation is dependent on the nucleation and growth times, which are controlled by laser energy density and thermal conductivities of substrate and as-deposited thin film. The diamond nuclei present in the Q-carbon structure ( 80% sp 3) can also be grown to larger sizes using the equilibrium hot filament chemical vapor deposition process. The texture of diamond and c-BN crystals is <111> under epitaxial growth and <110> under rapid unseeded crystallization. Our nanosecond laser processing opens up a roadmap to the fabrication of novel phases on heat-sensitive substrates.

The impact trajectory of asteroid 2008 TC3

NASA Astrophysics Data System (ADS)

Farnocchia, Davide; Jenniskens, Peter; Robertson, Darrel K.; Chesley, Steven R.; Dimare, Linda; Chodas, Paul W.

2017-09-01

The impact of asteroid 2008 TC3 was an unprecedented event-the first ever predicted impact of a near-Earth object. When it was first detected about 20 h before impact, 2008 TC3 was still farther away than the Moon. Once it was recognized as an impactor and announced as such, 2008 TC3 began to receive considerable attention from astronomical observers. Using the unprecedented dataset of nearly 900 astrometric observations and the latest observation debiasing and weighting techniques, we estimate the precise trajectory of 2008 TC3 and its impact ground track. At the entry point into the atmosphere, the 3-σ formal uncertainty in predicted position is an ellipse only 1.4 km × 0.15 km in size. The locations of the many meteorites recovered from the desert floor mark the asteroid's actual ground track and provide a unique opportunity to validate trajectory models. We find that the second-order zonal harmonics of the Earth gravity field moves the ground track by more than 1 km and the location along the ground track by more than 2 km, while non-zonal and higher order harmonics change the impact prediction by less than 20 m. The contribution of atmospheric drag to the trajectory of 2008 TC3 is similar to the numerical integration error level, a few meters, down to an altitude of 50 km. Integrating forward to lower altitudes and ignoring the break-up of 2008 TC3, atmospheric drag causes an along-track deviation that can be as large as a few kilometers at sea level.

Evaluation of somatostatin receptors in large cell pulmonary neuroendocrine carcinoma with 99mTc-EDDA/HYNIC-TOC scintigraphy.

PubMed

Nocuń, Anna; Chrapko, Beata; Gołębiewska, Renata; Stefaniak, Bogusław; Czekajska-Chehab, Elżbieta

2011-06-01

Large cell pulmonary neuroendocrine carcinoma (LCNEC) is a poorly differentiated and high-grade neoplasm. It is positioned between an atypical carcinoid and small cell neuroendocrine carcinoma of the lung in a distinct family of pulmonary neuroendocrine tumors. The aim of our study was to detect somatostatin receptors in this uncommon malignancy and to evaluate the sensitivity of somatostatin receptor scintigraphy (SRS) in LCNEC staging. We analyzed data of 26 patients (mean age: 61.5±7.9 years) with histologically confirmed diagnosis of LCNEC, including 18 cases not treated surgically and eight patients after the resection of the primary tumor. SRS was carried out with technetium-99m ethylene diamine-diacetic acid/hydrazinonicotinyl-Tyr3-octreotide (Tc-TOC). A visual analysis of scintigraphic images was done with reference to conventional imaging modalities (computed tomography and bone sicintigraphy). SRS sensitivity for the detection of primary lesions, supradiaphragmatic metastases, and infradiaphragmatic metastases was 100, 83.3%, and 0%, respectively. Five out of 13 metastases to the liver appeared on SRS as photopenic foci, visible on the background of physiological hepatic activity. Only one of the nine metastases to the skeletal system was found by SRS with sensitivity as low as 11.1%. The overall SRS sensitivity for the detection of secondary lesions and of all lesions was 54.8 and 62.2%, respectively. Within a rather large series of LCNEC, the primary tumor showed an uptake of Tc-TOC in all cases, whereas some metastases did show Tc-TOC uptake and some others did not.

Improved Quantification of the Beta Cell Mass after Pancreas Visualization with 99mTc-demobesin-4 and Beta Cell Imaging with 111In-exendin-3 in Rodents.

PubMed

van der Kroon, Inge; Joosten, Lieke; Nock, Berthold A; Maina, Theodosia; Boerman, Otto C; Brom, Maarten; Gotthardt, Martin

2016-10-03

Accurate assessment of the 111 In-exendin-3 uptake within the pancreas requires exact delineation of the pancreas, which is highly challenging by MRI and CT in rodents. In this study, the pancreatic tracer 99m Tc-demobesin-4 was evaluated for accurate delineation of the pancreas to be able to accurately quantify 111 In-exendin-3 uptake within the pancreas. Healthy and alloxan-induced diabetic Brown Norway rats were injected with the pancreatic tracer 99m Tc-demobesin-4 ([ 99m Tc-N 4 -Pro 1 ,Tyr 4 ,Nle 14 ]bombesin) and the beta cell tracer 111 In-exendin-3 ([ 111 In-DTPA-Lys 40 ]exendin-3). After dual isotope acquisition of SPECT images, 99m Tc-demobesin-4 was used to define a volume of interest for the pancreas in SPECT images subsequently the 111 In-exendin-3 uptake within this region was quantified. Furthermore, biodistribution and autoradiography were performed in order to gain insight in the distribution of both tracers in the animals. 99m Tc-demobesin-4 showed high accumulation in the pancreas. The uptake was highly homogeneous throughout the pancreas, independent of diabetic status, as demonstrated by autoradiography, whereas 111 In-exendin-3 only accumulates in the islets of Langerhans. Quantification of both ex vivo and in vivo SPECT images resulted in an excellent linear correlation between the pancreatic uptake, determined with ex vivo counting and 111 In-exendin-3 uptake, determined from the quantitative analysis of the SPECT images (Pearson r = 0.97, Pearson r = 0.92). 99m Tc-demobesin-4 shows high accumulation in the pancreas of rats. It is a suitable tracer for accurate delineation of the pancreas and can be conveniently used for simultaneous acquisition with 111 In labeled exendin-3. This method provides a straightforward, reliable, and objective method for preclinical beta cell mass (BCM) quantification with 111 In-exendin-3.

Characterization of the Lytic Capability of a LysK-Like Endolysin, Lys-phiSA012, Derived from a Polyvalent Staphylococcus aureus Bacteriophage

PubMed Central

Nakamura, Tomohiro; Furusawa, Takaaki; Ohno, Hazuki; Takahashi, Hiromichi; Kitana, Junya; Usui, Masaru; Higuchi, Hidetoshi; Tamura, Yutaka

2018-01-01

Antibiotic-resistant bacteria (ARB) have spread widely and rapidly, with their increased occurrence corresponding with the increased use of antibiotics. Infections caused by Staphylococcus aureus have a considerable negative impact on human and livestock health. Bacteriophages and their peptidoglycan hydrolytic enzymes (endolysins) have received significant attention as novel approaches against ARB, including S. aureus. In the present study, we purified an endolysin, Lys-phiSA012, which harbors a cysteine/histidine-dependent amidohydrolase/peptidase (CHAP) domain, an amidase domain, and a SH3b cell wall binding domain, derived from a polyvalent S. aureus bacteriophage which we reported previously. We demonstrate that Lys-phiSA012 exhibits high lytic activity towards staphylococcal strains, including methicillin-resistant S. aureus (MRSA). Analysis of deletion mutants showed that only mutants possessing the CHAP and SH3b domains could lyse S. aureus, indicating that lytic activity of the CHAP domain depended on the SH3b domain. The presence of at least 1 mM Ca2+ and 100 µM Zn2+ enhanced the lytic activity of Lys-phiSA012 in a turbidity reduction assay. Furthermore, a minimum inhibitory concentration (MIC) assay showed that the addition of Lys-phiSA012 decreased the MIC of oxacillin. Our results suggest that endolysins are a promising approach for replacing current antimicrobial agents and may contribute to the proper use of antibiotics, leading to the reduction of ARB. PMID:29495305

Electrophoretic Deposition of Chitosan/h-BN and Chitosan/h-BN/TiO2 Composite Coatings on Stainless Steel (316L) Substrates

PubMed Central

Raddaha, Namir S.; Cordero-Arias, Luis; Cabanas-Polo, Sandra; Virtanen, Sannakaisa; Roether, Judith A.; Boccaccini, Aldo R.

2014-01-01

This article presents the results of an experimental investigation designed to deposit chitosan/hexagonal boron nitride (h-BN) and chitosan/h-BN/titania (TiO2) composites on SS316L substrates using electrophoretic deposition (EPD) for potential antibacterial applications. The influence of EPD parameters (voltage and deposition time) and relative concentrations of chitosan, h-BN and TiO2 in suspension on deposition yield was studied. The composition and structure of deposited coatings were investigated by FTIR, XRD and SEM. It was observed that h-BN and TiO2 particles were dispersed in the chitosan matrix through simultaneous deposition. The adhesion between the electrophoretic coatings and the stainless steel substrates was tested by using tape test technique, and the results showed that the adhesion strength corresponded to 3B and 4B classes. Corrosion resistance was evaluated by electrochemical polarization curves, indicating enhanced corrosion resistance of the chitosan/h-BN/TiO2 and chitosan/h-BN coatings compared to the bare stainless steel substrate. In order to investigate the in-vitro inorganic bioactivity, coatings were immersed in simulated body fluid (SBF) for 28 days. FTIR and XRD results showed no formation of hydroxyapatite on the surface of chitosan/h-BN/TiO2 and chitosan/h-BN coatings, which are therefore non bioactive but potentially useful as antibacterial coatings. PMID:28788541

Evolutionary genomics of LysM genes in land plants.

PubMed

Zhang, Xue-Cheng; Cannon, Steven B; Stacey, Gary

2009-08-03

The ubiquitous LysM motif recognizes peptidoglycan, chitooligosaccharides (chitin) and, presumably, other structurally-related oligosaccharides. LysM-containing proteins were first shown to be involved in bacterial cell wall degradation and, more recently, were implicated in perceiving chitin (one of the established pathogen-associated molecular patterns) and lipo-chitin (nodulation factors) in flowering plants. However, the majority of LysM genes in plants remain functionally uncharacterized and the evolutionary history of complex LysM genes remains elusive. We show that LysM-containing proteins display a wide range of complex domain architectures. However, only a simple core architecture is conserved across kingdoms. Each individual kingdom appears to have evolved a distinct array of domain architectures. We show that early plant lineages acquired four characteristic architectures and progressively lost several primitive architectures. We report plant LysM phylogenies and associated gene, protein and genomic features, and infer the relative timing of duplications of LYK genes. We report a domain architecture catalogue of LysM proteins across all kingdoms. The unique pattern of LysM protein domain architectures indicates the presence of distinctive evolutionary paths in individual kingdoms. We describe a comparative and evolutionary genomics study of LysM genes in plant kingdom. One of the two groups of tandemly arrayed plant LYK genes likely resulted from an ancient genome duplication followed by local genomic rearrangement, while the origin of the other groups of tandemly arrayed LYK genes remains obscure. Given the fact that no animal LysM motif-containing genes have been functionally characterized, this study provides clues to functional characterization of plant LysM genes and is also informative with regard to evolutionary and functional studies of animal LysM genes.

The utility of two somatostatin analog radiopharmaceuticals in assessment of radiologically indeterminate pulmonary lesions.

PubMed

Sobic-Saranovic, Dragana P; Pavlovic, Smiljana V; Artiko, Vera M; Saranovic, Djordjije Z; Jaksic, Emilija D; Subotic, Dragan; Nagorni-Obradovic, Ljudmila; Kozarevic, Nebojsa; Petrovic, Nebojsa; Grozdic, Isidora T; Obradovic, Vladimir B

2012-01-01

The aim of our study was to assess diagnostic accuracy of Tc-99m depreotide and Tc-99m-EDDA/HYNIC-TOC scintigraphy for evaluation of pulmonary lesions that appeared ambiguous on computed tomography (CT). Forty-nine consecutive patients (37 men and 12 women; mean age, 60 ± 11 years) with 60 pulmonary lesions on chest radiography and CT were referred for nuclear imaging. They were prospectively allocated to undergo whole-body scintigraphy (WBS) and single photon emission computed tomography (SPECT) using either Tc-99m depreotide (26 patients, group 1) or Tc-99m-EDDA/HYNIC-TOC imaging (23 patients, group 2). Histologic findings after tissue biopsy served as a gold standard for determining diagnostic accuracy of the 2 somatostatin analogs. Visual assessment was complemented by semiquantitative analysis based on target to background ratio. Among the 32 pulmonary lesions scanned with Tc-99m depreotide, focal uptake was increased in 22 of 25 malignancies, whereas no uptake was found in 6 of 7 benign lesions (88% sensitivity, 85% specificity, and 88% accuracy) on both WBS and SPECT. Imaging of 28 pulmonary lesions with Tc-99m-EDDA/HYNIC-TOC had a similar diagnostic yield (sensitivity 87%, specificity 84%, and accuracy 86%). Overall, target to background ratios were higher on SPECT than WBS but not significantly different between groups 1 and 2 (SPECT 2.72 ± 0.70 vs. 2.71 ± 0.50, WBS 1.61 ± 0.32 vs. 1.62 ± 0.28, respectively). This study demonstrates that Tc-99m depreotide and Tc-99m-EDDA/HYNIC-TOC have similar diagnostic value for characterizing pulmonary lesions that appear ambiguous on CT.

Development of a (99m)Tc-labeled lactam bridge-cyclized alpha-MSH derivative peptide as a possible single photon imaging agent for melanoma tumors.

PubMed

Shamshirian, Danial; Erfani, Mostafa; Beiki, Davood; Fallahi, Babak; Shafiei, Mohammad

2015-10-01

Melanocortin-1 (MC1) receptor is an attractive melanoma-specific target which has been used for melanoma imaging and therapy. In this work, a new lactam bridge α-MSH analog was labeled with (99m)Tc via HYNIC and EDDA/tricine as coligands including gamma aminobutyric acid (GABA) as a three carbon chain spacer between HYNIC and the N-terminus of the cyclic peptide. Also, stability in human serum, receptor bound internalization, in vivo tumor uptake, and tissue biodistribution were thoroughly investigated. HYNIC-GABA-Nle-CycMSHhept was synthesized using a standard Fmoc strategy. Labeling was performed at 95 °C and analysis involved instant thin layer chromatography and high performance liquid chromatography methods. The receptor bound internalization rate was studied in MC1 receptor expressing B16/F10 cells. Biodistribution of radiopeptide was studied in nude mice bearing B16/F10 tumor. Labeling yield of >98 % (n = 3) was obtained corresponding to a specific activity of 81 MBq/nmol. Peptide conjugate showed efficient stability in the presence of human serum. The radioligand showed specific internalization into B16/F10 cells (12.45 ± 1.1 % at 4 h). In biodistribution studies, a receptor-specific uptake was observed in MC1 receptor-positive organs so that after 2 h the uptake in mouse tumor was 5.10 ± 0.08 % ID/g, while low accumulation in the kidney uptake was observed (4.58 ± 0.68 % ID/g at 2 h after injection). The obtained results show that the presented new designed labeled peptide conjugate may be a suitable candidate for diagnosis of malignant tumors.

Effect of the melanocortin-3 receptor Thr6Lys and Val81Ile genetic variants on body composition and substrate oxidation in Chilean obese children.

PubMed

Obregón, Ana M; Diaz, Erik; Santos, Jose L

2012-03-01

Mice genetically deficient in the melanocortin-3 receptor gene are characterized by normal body weight, increased body fat, mild hypophagia, reduced locomotor activity, and increased respiratory quotient compared with wild-type mice. In humans, the 6Lys-81Ile haplotype of melanocortin-3 receptor (MC3R) gene has been associated with childhood obesity, higher body fat percentage, and reduced fat oxidation compared to non-carriers. The aim of this study was to evaluate the association between MC3R 6Lys-81Ile haplotype with body composition and substrate oxidation in response to moderate exercise in obese children. Eight Chilean obese children (aged 8-12) carriers of MC3R 6Lys-81Ile haplotype were compared with eight age-gender-matched obese non-carriers. Children were identified through a previous cross-sectional study on genetic determinants of childhood obesity (n = 229). Genotypes for MC3R Thr6Lys and Val81Ile were determined by polymerase chain reaction-restriction fragment length polymorphism. Body composition was assessed by the four-compartment model (dual-energy X-ray absorptiometry, total body water by the deuterium dilution technique, and total fat mass by air-displacement plethysmography). Substrate oxidation was assessed by indirect calorimetry in response to moderate exercise (60% VO(2 max)). Wilcoxon matched-pairs test was used to compare quantitative variables. No significant differences among carriers and non-carriers were found in anthropometrical and body composition measurements. The Carriers of the 6Lys-81Ile haplotype showed higher respiratory quotient (p = 0.06) and a significantly higher glucose oxidation (p = 0.01) compared with non-carriers after standardization for fat-free mass. Our results are consistent with a possible participation of MC3R 6Lys-81Ile variants in glucose oxidation in response to moderate exercise.

Effect of the SiCl4 Flow Rate on SiBN Deposition Kinetics in SiCl4-BCl3-NH3-H2-Ar Environment

PubMed Central

Li, Jianping; Qin, Hailong; Liu, Yongsheng; Ye, Fang; Li, Zan; Cheng, Laifei; Zhang, Litong

2017-01-01

To improve the thermal and mechanical stability of SiCf/SiC or C/SiC composites with SiBN interphase, SiBN coating was deposited by low pressure chemical vapor deposition (LPCVD) using SiCl4-BCl3-NH3-H2-Ar gas system. The effect of the SiCl4 flow rate on deposition kinetics was investigated. Results show that deposition rate increases at first and then decreases with the increase of the SiCl4 flow rate. The surface of the coating is a uniform cauliflower-like structure at the SiCl4 flow rate of 10 mL/min and 20 mL/min. The surface is covered with small spherical particles when the flow rate is 30 mL/min. The coatings deposited at various SiCl4 flow rates are all X-ray amorphous and contain Si, B, N, and O elements. The main bonding states are B-N, Si-N, and N-O. B element and B-N bonding decrease with the increase of SiCl4 flow rate, while Si element and Si-N bonding increase. The main deposition mechanism refers to two parallel reactions of BCl3+NH3 and SiCl4+NH3. The deposition process is mainly controlled by the reaction of BCl3+NH3. PMID:28772986

Human tRNA(Lys3)(UUU) is pre-structured by natural modifications for cognate and wobble codon binding through keto-enol tautomerism.

PubMed

Vendeix, Franck A P; Murphy, Frank V; Cantara, William A; Leszczyńska, Grażyna; Gustilo, Estella M; Sproat, Brian; Malkiewicz, Andrzej; Agris, Paul F

2012-03-02

Human tRNA(Lys3)(UUU) (htRNA(Lys3)(UUU)) decodes the lysine codons AAA and AAG during translation and also plays a crucial role as the primer for HIV-1 (human immunodeficiency virus type 1) reverse transcription. The posttranscriptional modifications 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U(34)), 2-methylthio-N(6)-threonylcarbamoyladenosine (ms(2)t(6)A(37)), and pseudouridine (Ψ(39)) in the tRNA's anticodon domain are critical for ribosomal binding and HIV-1 reverse transcription. To understand the importance of modified nucleoside contributions, we determined the structure and function of this tRNA's anticodon stem and loop (ASL) domain with these modifications at positions 34, 37, and 39, respectively (hASL(Lys3)(UUU)-mcm(5)s(2)U(34);ms(2)t(6)A(37);Ψ(39)). Ribosome binding assays in vitro revealed that the hASL(Lys3)(UUU)-mcm(5)s(2)U(34);ms(2)t(6)A(37);Ψ(39) bound AAA and AAG codons, whereas binding of the unmodified ASL(Lys3)(UUU) was barely detectable. The UV hyperchromicity, the circular dichroism, and the structural analyses indicated that Ψ(39) enhanced the thermodynamic stability of the ASL through base stacking while ms(2)t(6)A(37) restrained the anticodon to adopt an open loop conformation that is required for ribosomal binding. The NMR-restrained molecular-dynamics-derived solution structure revealed that the modifications provided an open, ordered loop for codon binding. The crystal structures of the hASL(Lys3)(UUU)-mcm(5)s(2)U(34);ms(2)t(6)A(37);Ψ(39) bound to the 30S ribosomal subunit with each codon in the A site showed that the modified nucleotides mcm(5)s(2)U(34) and ms(2)t(6)A(37) participate in the stability of the anticodon-codon interaction. Importantly, the mcm(5)s(2)U(34)·G(3) wobble base pair is in the Watson-Crick geometry, requiring unusual hydrogen bonding to G in which mcm(5)s(2)U(34) must shift from the keto to the enol form. The results unambiguously demonstrate that modifications pre-structure the anticodon as a key

h-BN Nanosheets as 2D Substrates to Load 0D Fe3O4 Nanoparticles: A Hybrid Anode Material for Lithium-Ion Batteries.

PubMed

Duan, Zhi-Qiang; Liu, Yi-Tao; Xie, Xu-Ming; Ye, Xiong-Ying; Zhu, Xiao-Dong

2016-03-18

h-BN, as an isoelectronic analogue of graphene, has improved thermal mechanical properties. Moreover, the liquid-phase production of h-BN is greener since harmful oxidants/reductants are unnecessary. Here we report a novel hybrid architecture by employing h-BN nanosheets as 2D substrates to load 0D Fe3O4 nanoparticles, followed by phenol/formol carbonization to form a carbon coating. The resulting carbon-encapsulated h-BN@Fe3O4 hybrid architecture exhibits synergistic interactions: 1) The h-BN nanosheets act as flexible 2D substrates to accommodate the volume change of the Fe3O4 nanoparticles; 2) The Fe3O4 nanoparticles serve as active materials to contribute to a high specific capacity; and 3) The carbon coating not only protects the hybrid architecture from deformation but also keeps the whole electrode highly conductive. The synergistic interactions translate into significantly enhanced electrochemical performances, laying a basis for the development of superior hybrid anode materials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Risk of type 2 diabetes mellitus in the Kyrgyz population in the presence of ADIPOQ (G276T), KCNJ11 (Glu23Lys), TCF7L2 (IVS3C>T) gene polymorphisms].

PubMed

Isakova, Zh T; Talaibekova, E T; Asambaeva, D A; Kerimkulova, A S; Lunegova, O S; Aldasheva, N M; Aldashev, A A

To analyze the association of genotype combinations of the polymorphic markers G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene with the development of type 2 diabetes mellitus (T2DM) in the Kyrgyz population. The investigation enrolled 23 Kyrgyz people, of whom there were 114 patients with T2DM and 109 without T2DM (a control group). T2DM was diagnosed in accordance with the WHO criteria (1999). The genotypes of ADIPOQ (G276T), KCNJ11 (Glu23Lys), and TCF7L2 (IVS3C>T) gene polymorphisms were identified using the restriction fragment length polymorphism analysis. When typing at the polymorphic loci G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene, the development of T2DM in the Kyrgyz population was associated with the T allele (odds ratio (OR), 1.68; p=0.025), the heterozygous G276T genotype (OR 1,8; p=0.036) in the ADIPOQ gene; the 23Lys allele (OR, 1.62; p=0.019) in the KCNJ11 gene; a two-locus genotype combination in the genes ADIPOQ/KCNJ11: G276T/Glu23Lys (OR, 4.88; p=0.0013), G276G/Lys23Lys (OR, 4.65; p=0.019), G276T/Glu23Glu (OR, 3.10; p=0.022), a two-locus genotype combination in the genes ADIPOQ/TCF7L2: G276T/СС (OR, 1.97; p=0.04); two-locus genotype combinations in the genes KCNJ11/TCF7L2: Lys23Lys/CC (ОR, 2.65; p=0.042), Glu23Lys/CT (OR, 3.88; p=0.027); and a three-locus genotype combination in the genes ADIPOQ/KCNJ11/TCF7L2: G276T/Glu23Lys/CT (OR, 14.48; p=0.02). The development of T2DM in the Kyrgyz population is genetically determined by ADIPOQ (G276T) gene, KCNJ11 (Glu23Lys), and TCF7L (IVS3C>T) gene polymorphisms with the predisposing value of the T allele of the heterozygous G276T genotype in the ADIPOQ gene; the 23Lys allele in the KCNJ1 gene; as well as by genotype combinations in the genes ADIPOQ/KCNJ11 (G276T/Glu23Lys, G276G/Lys23Lys, G276T/Glu23Glu); ADIPOQ/TCF7L2 (G276T/SS); KCNJ11/TCF7L2 (Lys23Lys/CC, Glu23Lys/CT); ADIPOQ/KCNJ11/TCF7L2 (G276T/Glu23Lys /CT). The IVS3C

In low transpiring conditions, uncoupling the BnNrt2.1 and BnNrt1.1 NO3- transporters by glutamate treatment reveals the essential role of BnNRT2.1 for nitrate uptake and the nitrate-signaling cascade during growth

PubMed Central

Leblanc, Antonin; Segura, Raphaël; Deleu, Carole; Le Deunff, Erwan

2013-01-01

In plants, the nitrate transporters, NRT1.1 and NRT2.1, are mainly responsible for nitrate uptake. Intriguingly, both nitrate transporters are located in a complementary manner in different cells layers of the mature root suggesting that their coordination should occur during nitrate uptake and plant growth. This hypothesis was examined on 5-d-old rape seedlings grown on agar medium supplemented with 1 or 5mM nitrate. Seedlings were treated with increasing potassium glutamate concentrations in order to uncouple the two nitrate transporters by inhibiting BnNRT2.1 expression and activity specifically. In both nitrate treatments, increasing the glutamate concentrations from 0.5 to 10mM induced a reduction in 15NO3- uptake and an inhibition of N assimilation. The decrease in 15NO3- uptake was caused by downregulation of BnNRT2.1 expression but surprisingly it was not compensated by the upregulation of BnNRT1.1. This created an unprecedented physiological situation where the effects of the nitrate signal on shoot growth were solely modulated by nitrate absorption. In these conditions, the osmotic water flow for volumetric shoot growth was mainly dependent on active nitrate transport and nitrate signaling. This behavior was confirmed by the allometric relationships found between changes in the root length with 15N and water accumulation in the shoot. These findings demonstrate that the BnNRT2.1 transporter is essential for nitrate uptake and growth, and renew the question of the respective roles of the NRT2.1 and NRT1.1 transporters in nitrate uptake and sensing at the whole plant level. PMID:23299418

SARS Coronavirus Papain-Like Protease Inhibits the TLR7 Signaling Pathway through Removing Lys63-Linked Polyubiquitination of TRAF3 and TRAF6.

PubMed

Li, Shih-Wen; Wang, Ching-Ying; Jou, Yu-Jen; Huang, Su-Hua; Hsiao, Li-Hsin; Wan, Lei; Lin, Ying-Ju; Kung, Szu-Hao; Lin, Cheng-Wen

2016-05-05

Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLPro) reportedly inhibits the production of type I interferons (IFNs) and pro-inflammatory cytokines in Toll-like receptor 3 (TLR3) and retinoic acid-inducible gene 1 (RIG-I) pathways. The study investigated the inhibitory effect and its antagonistic mechanism of SARS-CoV PLPro on TLR7-mediated cytokine production. TLR7 agonist (imiquimod (IMQ)) concentration-dependently induced activation of ISRE-, NF-κB- and AP-1-luciferase reporters, as well as the production of IFN-α, IFN-β, TNF-α, IL-6 and IL-8 in human promonocyte cells. However, SARS-CoV PLPro significantly inhibited IMQ-induced cytokine production through suppressing the activation of transcription factors IRF-3, NF-κB and AP-1. Western blot analysis with anti-Lys48 and anti-Lys63 ubiquitin antibodies indicated the SARS-CoV PLPro removed Lys63-linked ubiquitin chains of TRAF3 and TRAF6, but not Lys48-linked ubiquitin chains in un-treated and treated cells. The decrease in the activated state of TRAF3 and TRAF6 correlated with the inactivation of TBK1 in response to IMQ by PLPro. The results revealed that the antagonism of SARS-CoV PLPro on TLR7-mediated innate immunity was associated with the negative regulation of TRAF3/6-TBK1-IRF3/NF-κB/AP1 signals.

On the Stability of c-BN-Reinforcing Particles in Ceramic Matrix Materials

PubMed Central

Wolfrum, Anne-Kathrin; Michaelis, Alexander; Herrmann, Mathias

2018-01-01

Cubic boron nitride (c-BN) composites produced at high pressures and temperatures are widely used as cutting tool materials. The advent of new, effective pressure-assisted densification methods, such as spark plasma sintering (SPS), has stimulated attempts to produce these composites at low pressures. Under low-pressure conditions, however, transformation of c-BN to the soft hexagonal BN (h-BN) phase can occur, with a strong deterioration in hardness and wear. In the present work, the influence of secondary phases (B2O3, Si3N4, and oxide glasses) on the transformation of c-BN was studied in the temperature range between 1100 °C and 1575 °C. The different heat treated c-BN particles and c-BN composites were analyzed by SEM, X-ray diffraction, and Raman spectroscopy. The transformation mechanism was found to be kinetically controlled solution–diffusion–precipitation. Given a sufficiently low liquid phase viscosity, the transformation could be observed at temperatures as low as 1200 °C for the c-BN–glass composites. In contrast, no transformation was found at temperatures up to 1575 °C when no liquid oxide phase is present in the composite. The results were compared with previous studies concerning the c-BN stability and the c-BN phase diagram. PMID:29414847

Spectroscopic Characterization of Aqua [ fac-Tc(CO)3]+ Complexes at High Ionic Strength.

PubMed

Chatterjee, Sayandev; Hall, Gabriel B; Engelhard, Mark H; Du, Yingge; Washton, Nancy M; Lukens, Wayne W; Lee, Sungsik; Pearce, Carolyn I; Levitskaia, Tatiana G

2018-06-18

Understanding fundamental Tc chemistry is important to both the remediation of nuclear waste and the reprocessing of nuclear fuel; however, current knowledge of the electronic structure and spectral signatures of low-valent Tc compounds significantly lags behind the remainder of the d-block elements. In particular, identification and treatment of Tc speciation in legacy nuclear waste is challenging due to the lack of reference data especially for Tc compounds in the less common oxidation states (I-VI). In an effort to establish a spectroscopic library corresponding to the relevant conditions of extremely high ionic strength typical for the legacy nuclear waste, compounds with the general formula of [ fac-Tc(CO) 3 (OH 2 ) 3- n (OH) n ] 1- n (where n = 0-3) were examined by a range of spectroscopic techniques including 99 Tc/ 13 C NMR, IR, XPS, and XAS. In the series of monomeric aqua species, stepwise hydrolysis results in the increase of the Tc metal center electron density and corresponding progressive decrease of the Tc-C bond distances, Tc electron binding energies, and carbonyl stretching frequencies in the order [ fac-Tc(CO) 3 (OH 2 ) 3 ] + > [ fac-Tc(CO) 3 (OH 2 ) 2 (OH)] > [ fac-Tc(CO) 3 (OH 2 )(OH) 2 ] - . These results correlate with established trends of the 99 Tc upfield chemical shift and carbonyl 13 C downfield chemical shift. The lone exception is [ fac-Tc(CO) 3 (OH)] 4 which exhibits a comparatively low electron density at the metal center attributed to the μ 3 -bridging nature of the - OH ligands causing less σ-donation and no π-donation. This work also reports the first observations of these compounds by XPS and [ fac-Tc(CO) 3 Cl 3 ] 2- by XAS. The unique and distinguishable spectral features of the aqua [ fac-Tc(CO) 3 ] + complexes lay the foundation for their identification in the complex aqueous matrixes.

One-pot synthesis of h-BN fullerenes usinsg a graphene oxide template

NASA Astrophysics Data System (ADS)

Kim, Sang Sub; Khai, Tran Van; Kwon, Yong Jung; Katoch, Akash; Wu, Ping; Kim, Hyoun Woo

2015-09-01

Hexagonal-boron nitride ( h-BN) fullerenes were synthesized from a graphene oxide (GO) template by simultaneously heating the GO and B2O3 in the presence of NH3 gas. Transmission electron microscopy (TEM) observations revealed that a considerable amount of product had a fullerene-like nanostructure. Typical BN fullerenes have a polyhedral shape, being hollow nanocages. Lattice-resolved TEM and X-ray diffraction consistently demonstrated the formation of h-BN fullerenes. The FTIR spectrum exhibited absorption bands at approximately 800 and 1378 cm-1, which were related to the h-BN structure. The Raman spectra exhibited peaks at 1368 and 1399 cm-1, which can be related to BN sheets and BN fullerenes, respectively. The photoluminescence spectrum of the h-BN fullerenes taken at 8 K exhibited intense white-light emission. To reveal the origin of the broad emission band, which could be a superimposition of several peaks, we used a deconvolution procedure based on Gaussian functions. We proposed a growth mechanism of the h-BN fullerenes and verified it with a thermodynamic calculation. This work provides a cost-effective approach to synthesize fullerene-type boron nitride on a production scale.

New nano-sized Al2O3-BN coating 3Y-TZP ceramic composites for CAD/CAM-produced all-ceramic dental restorations. Part I. Fabrication of powders.

PubMed

Yang, Se Fei; Yang, Li Qiang; Jin, Zhi Hao; Guo, Tian Wen; Wang, Lei; Liu, Hong Chen

2009-06-01

Partially sintered 3 mol % yttria-stabilized tetragonal zirconium dioxide (ZrO(2), zirconia) polycrystal (3Y-TZP) ceramics are used in dental posterior restorations with computer-aided design-computer-aided manufacturing (CAD/CAM) techniques. High strength is acquired after sintering, but shape distortion of preshaped compacts during their sintering is inevitable. The aim of this study is to fabricate new machinable ceramic composites with strong mechanical properties that are fit for all-ceramic dental restorations. Aluminum oxide (Al(2)O(3))-coated 3Y-TZP powders were first prepared by the heterogeneous precipitation method starting with 3Y-TZP, Al(NO(3))(3) . 9H(2)O, and ammonia, then amorphous boron nitride (BN) was produced and the as-received composite powders were coated via in situ reaction with boric acid and urea. Transmission electron microscopy (TEM) and X-ray diffraction (XRD) were used to analyze the status of Al(2)O(3)-BN on the surface of the 3Y-TZP particles. TEM micrographs show an abundance of Al(2)O(3) particles and amorphous BN appearing uniformly on the surface of the 3Y-TZP particles after the coating process. The size of the Al(2)O(3) particles is about 20 nm. The XRD pattern shows clearly the peak of amorphous BN among the peaks of ZrO(2).

Vibrational Properties of h-BN and h-BN-Graphene Heterostructures Probed by Inelastic Electron Tunneling Spectroscopy

PubMed Central

Jung, Suyong; Park, Minkyu; Park, Jaesung; Jeong, Tae-Young; Kim, Ho-Jong; Watanabe, Kenji; Taniguchi, Takashi; Ha, Dong Han; Hwang, Chanyong; Kim, Yong-Sung

2015-01-01

Inelastic electron tunneling spectroscopy is a powerful technique for investigating lattice dynamics of nanoscale systems including graphene and small molecules, but establishing a stable tunnel junction is considered as a major hurdle in expanding the scope of tunneling experiments. Hexagonal boron nitride is a pivotal component in two-dimensional Van der Waals heterostructures as a high-quality insulating material due to its large energy gap and chemical-mechanical stability. Here we present planar graphene/h-BN-heterostructure tunneling devices utilizing thin h-BN as a tunneling insulator. With much improved h-BN-tunneling-junction stability, we are able to probe all possible phonon modes of h-BN and graphite/graphene at Γ and K high symmetry points by inelastic tunneling spectroscopy. Additionally, we observe that low-frequency out-of-plane vibrations of h-BN and graphene lattices are significantly modified at heterostructure interfaces. Equipped with an external back gate, we can also detect high-order coupling phenomena between phonons and plasmons, demonstrating that h-BN-based tunneling device is a wonderful playground for investigating electron-phonon couplings in low-dimensional systems. PMID:26563740

Vibrational Properties of h-BN and h-BN-Graphene Heterostructures Probed by Inelastic Electron Tunneling Spectroscopy.

PubMed

Jung, Suyong; Park, Minkyu; Park, Jaesung; Jeong, Tae-Young; Kim, Ho-Jong; Watanabe, Kenji; Taniguchi, Takashi; Ha, Dong Han; Hwang, Chanyong; Kim, Yong-Sung

2015-11-13

Inelastic electron tunneling spectroscopy is a powerful technique for investigating lattice dynamics of nanoscale systems including graphene and small molecules, but establishing a stable tunnel junction is considered as a major hurdle in expanding the scope of tunneling experiments. Hexagonal boron nitride is a pivotal component in two-dimensional Van der Waals heterostructures as a high-quality insulating material due to its large energy gap and chemical-mechanical stability. Here we present planar graphene/h-BN-heterostructure tunneling devices utilizing thin h-BN as a tunneling insulator. With much improved h-BN-tunneling-junction stability, we are able to probe all possible phonon modes of h-BN and graphite/graphene at Γ and K high symmetry points by inelastic tunneling spectroscopy. Additionally, we observe that low-frequency out-of-plane vibrations of h-BN and graphene lattices are significantly modified at heterostructure interfaces. Equipped with an external back gate, we can also detect high-order coupling phenomena between phonons and plasmons, demonstrating that h-BN-based tunneling device is a wonderful playground for investigating electron-phonon couplings in low-dimensional systems.

Novel 99mTc(III)-azide complexes [99mTc(N3)(CDO)(CDOH)2B-R] (CDOH2=cyclohexanedione dioxime) as potential radiotracers for heart imaging.

PubMed

Liu, Min; Zheng, Yumin; Avcibasi, Ugur; Liu, Shuang

2016-11-01

In this study, novel 99m Tc(III)-azide complexes [ 99m Tc(N 3 )(CDO)(CDOH) 2 B-R] ( 99m Tc-ISboroxime-N 3 : R=IS; 99m Tc-MPboroxime-N 3 : R=MP; 99m Tc-PAboroxime-N 3 : R=PA; 99m Tc-PYboroxime-N 3 : R=PY; and 99m Tc-Uboroxime-N 3 : R=5U) were evaluated as heart imaging agents. Complexes [ 99m Tc(N 3 )(CDO)(CDOH) 2 B-R] (R=IS, MP, PA, PY and 5U) were prepared by ligand exchange between NaN 3 and [ 99m TcCl(CDO)(CDOH) 2 B-R]. Biodistribution and imaging studies were carried out in Sprague-Dawley rats. Image quantification was performed to compare their initial heart uptake and myocardial retention. 99m Tc-ISboroxime-N 3 , 99m Tc-PYboroxime-N 3 and 99m Tc-Uboroxime-N 3 were prepared with high RCP (93-98%) while the RCP of 99m Tc-MPboroxime-N 3 and 99m Tc-PAboroxime-N 3 was 80-85%. The myocardial retention curves of 99m Tc-ISboroxime-N 3 , 99m Tc-PYboroxime-N 3 and 99m Tc-Uboroxime-N 3 were best fitted to the bi-exponential decay function. The half-time of the fast component was 1.6±0.4min for 99m Tc-ISboroxime-N 3 , 0.7±0.1min for 99m Tc-PYboroxime-N 3 and 0.9±0.4min for 99m Tc-Uboroxime-N 3 . The 2-min heart uptake from biodistribution studies followed the ranking order of 99m Tc-ISboroxime-N 3 (3.60±0.68%ID/g)> 99m Tc-PYboroxime-N 3 (2.35±0.37%ID/g)≫ 99m Tc-Uboroxime-N 3 (1.29±0.06%ID/g). 99m Tc-ISboroxime-N 3 had the highest 2-min heart uptake among 99m Tc radiotracers revaluated in SD rats. High quality SPECT images were obtained with the right and left ventricular walls being clearly delineated. The best image acquisition window was 0-5min for 99m Tc-ISboroxime-N 3 . Both azide coligand and boronate caps had significant impact on the heart uptake and myocardial retention of complexes [ 99m Tc(N 3 )(CDO)(CDOH) 2 B-R]. Among the radiotracers evaluated in SD rats, 99m Tc-ISboroxime-N 3 has the highest initial heart uptake with the heart retention comparable to that of 99m Tc-Teboroxime. 99m Tc-ISboroxime-N 3 is a promising alternative to 99m Tc-Teboroxime for

99mTc-3P4-RGD2 Scintimammography in the Assessment of Breast Lesions: Comparative Study with 99mTc-MIBI

PubMed Central

Gao, Shi; Ji, Tiefeng; Wen, Qiang; Song, Yan; Zhu, Lei; Xu, Zheli; Liu, Lin

2014-01-01

Purpose To compare the potential application of 99mTc-3P-Arg-Gly-Asp (99mTc-3P4-RGD2) scintimammography (SMM) and 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) SMM for the differentiation of malignant from benign breast lesions. Method Thirty-six patients with breast masses on physical examination and/or suspicious mammography results that required fine needle aspiration cytology biopsy (FNAB) were included in the study. 99mTc-3P4-RGD2 and 99mTc-MIBI SMM were performed with single photon emission computed tomography (SPECT) at 60 min and 20 min respectively after intravenous injection of 738±86 MBq radiotracers on a separate day. Images were evaluated by the tumor to non-tumor localization ratios (T/NT). Receiver operating characteristic (ROC) curve analysis was performed on each radiotracer to calculate the cut-off values of quantitative indices and to compare the diagnostic performance for the ability to differentiate malignant from benign diseases. Results The mean T/NT ratio of 99mTc-3P4-RGD2 in malignant lesions was significantly higher than that in benign lesions (3.54±1.51 vs. 1.83±0.98, p<0.001). The sensitivity, specificity, and accuracy of 99mTc-3P4-RGD2 SMM were 89.3%, 90.9% and 89.7%, respectively, with a T/NT cut-off value of 2.40. The mean T/NT ratio of 99mTc-MIBI in malignant lesions was also significantly higher than that in benign lesions (2.86±0.99 vs. 1.51±0.61, p<0.001). The sensitivity, specificity and accuracy of 99mTc-MIBI SMM were 87.5%, 72.7% and 82.1%, respectively, with a T/NT cut-off value of 1.45. According to the ROC analysis, the area under the curve for 99mTc-3P4-RGD2 SMM (area = 0.851) was higher than that for 99mTc-MIBI SMM (area = 0.781), but the statistical difference was not significant. Conclusion 99mTc-3P4-RGD2 SMM does not provide any significant advantage over the established 99mTc-MIBI SMM for the detection of primary breast cancer. The T/NT ratio of 99mTc-3P4-RGD2 SMM was significantly higher than that of 99mTc

Comparison of B{sub 2}O{sub 3} and BN deposited by atomic layer deposition for forming ultrashallow dopant regions by solid state diffusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Consiglio, Steven, E-mail: steve.consiglio@us.tel.com; Clark, Robert D.; O'Meara, David

2016-01-15

In this study, the authors investigated atomic layer deposition (ALD) of B{sub 2}O{sub 3} and BN for conformal, ultrashallow B doping applications and compared the effect of dopant-containing overlayers on sheet resistance (R{sub s}) and B profiles for both types of films subjected to a drive-in thermal anneal. For the deposition of B{sub 2}O{sub 3}, tris(dimethylamido)borane and O{sub 3} were used as coreactants and for the deposition of BN, BCl{sub 3} and NH{sub 3} were used as coreactants. Due to the extreme air instability of B{sub 2}O{sub 3} films, physical analysis was performed on B{sub 2}O{sub 3} films, which weremore » capped in-situ with ∼30 Å ALD grown Al{sub 2}O{sub 3} layers. For the BN films, in-situ ALD grown Si{sub 3}N{sub 4} capping layers (∼30 Å) were used for comparison. From spectroscopic ellipsometry, a thickness decrease was observed after 1000 °C, 30 s anneal for the B{sub 2}O{sub 3} containing stack with 60 ALD cycles of B{sub 2}O{sub 3}, whereas the BN containing stacks showed negligible thickness decrease after the annealing step, regardless of the number of BN cycles tested. The postanneal reduction in film thickness as well as decrease in R{sub s} for the B{sub 2}O{sub 3} containing stack suggests that the solid state diffusion dopant mechanism is effective, whereas for the BN containing stacks this phenomenon seems to be suppressed. Further clarification of the effectiveness of the B{sub 2}O{sub 3} containing layer compared to the film stacks with BN was evidenced in backside secondary ion mass spectrometry profiling of B atoms. Thus, B{sub 2}O{sub 3} formed by an ALD process and subsequently capped in-situ followed by a drive-in anneal offers promise as a dopant source for ultrashallow doping, whereas the same method using BN seems ineffective. An integrated approach for B{sub 2}O{sub 3} deposition and annealing on a clustered tool also demonstrated controllable R{sub s} reduction without the use of a capping layer.« less

Pulsed laser deposition of single layer, hexagonal boron nitride (white graphene, h-BN) on fiber-oriented Ag(111)/SrTiO3(001)

NASA Astrophysics Data System (ADS)

Velázquez, Daniel; Seibert, Rachel; Man, Hamdi; Spentzouris, Linda; Terry, Jeff

2016-03-01

We report on the growth of 1-10 ML films of hexagonal boron nitride (h-BN), also known as white graphene, on fiber-oriented Ag buffer films on SrTiO3(001) by pulsed laser deposition. The Ag buffer films of 40 nm thickness were used as substitutes for expensive single crystal metallic substrates. In-situ, reflection high-energy electron diffraction was used to monitor the surface structure of the Ag films and to observe the formation of the characteristic h-BN diffraction pattern. Further evidence of the growth of h-BN was provided by attenuated total reflectance spectroscopy, which showed the characteristic h-BN peaks at ˜780 cm-1 and 1367.4 cm-1. Ex-situ photoelectron spectroscopy showed that the surface of the h-BN films is stoichiometric. The physical structure of the films was confirmed by scanning electron microscopy. The h-BN films grew as large, sub-millimeter sheets with nano- and micro-sheets scattered on the surface. The h-BN sheets can be exfoliated by the micromechanical adhesive tape method. Spectral analysis was performed by energy dispersive spectroscopy in order to identify the h-BN sheets after exfoliation. The use of thin film Ag allows for reduced use of Ag and makes it possible to adjust the surface morphology of the thin film prior to h-BN growth.

UVB-induced nuclear translocation of TC-PTP by AKT/14-3-3σ axis inhibits keratinocyte survival and proliferation.

PubMed

Kim, Mihwa; Morales, Liza D; Baek, Minwoo; Slaga, Thomas J; DiGiovanni, John; Kim, Dae Joon

2017-10-31

Understanding protein subcellular localization is important to determining the functional role of specific proteins. T-cell protein tyrosine phosphatase (TC-PTP) contains bipartite nuclear localization signals (NLSI and NLSII) in its C-terminus. We previously have demonstrated that the nuclear form of TC-PTP (TC45) is mainly localized to the cytoplasm in keratinocytes and it is translocated to the nucleus following UVB irradiation. Here, we report that TC45 is translocated by an AKT/14-3-3σ-mediated mechanism in response to UVB exposure, resulting in increased apoptosis and decreased keratinocyte proliferation. We demonstrate that UVB irradiation increased phosphorylation of AKT and induced nuclear translocation of 14-3-3σ and TC45. However, inhibition of AKT blocked nuclear translocation of TC45 and 14-3-3σ. Site-directed mutagenesis of 14-3-3σ binding sites within TC45 showed that a substitution at Threonine 179 (TC45/T179A) effectively blocked UVB-induced nuclear translocation of ectopic TC45 due to the disruption of the direct binding between TC45 and 14-3-3σ. Overexpression of TC45/T179A in keratinocytes resulted in a decrease of UVB-induced apoptosis which corresponded to an increase in nuclear phosphorylated STAT3, and cell proliferation was higher in TC45/T179A-overexpressing keratinocytes compared to control keratinocytes following UVB irradiation. Furthermore, deletion of TC45 NLSII blocked its UVB-induced nuclear translocation, indicating that both T179 and NLSII are required. Taken together, our findings suggest that AKT and 14-3-3σ cooperatively regulate TC45 nuclear translocation in a critical step of an early protective mechanism against UVB exposure that signals the deactivation of STAT3 in order to promote keratinocyte cell death and inhibit keratinocyte proliferation.

Cellulose nanofibrils (CNF) filled boron nitride (BN) nanocomposites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sulaiman, Hanisah Syed; Hua, Chia Chin; Zakaria, Sarani

In this study, nanocomposite using cellulose nanofibrils filled with different percentage of boron nitride (CNF-BN) were prepared. The objective of this research is to study the effect of different percentage of BN to the thermal conductivity of the nanocomposite produced. The CNF-BN nanocomposite were characterization by FT-IR, SEM and thermal conductivity. The FT-IR analysis of the CNF-BN nanocomposite shows all the characteristic peaks of cellulose and BN present in all samples. The dispersion of BN in CNF were seen through SEM analysis. The effect of different loading percentage of BN to the thermal conductivity of the nanocomposite were also investigated.

A straightforward strategy toward large BN-embedded π-systems: synthesis, structure, and optoelectronic properties of extended BN heterosuperbenzenes.

PubMed

Wang, Xiao-Ye; Zhuang, Fang-Dong; Wang, Rui-Bo; Wang, Xin-Chang; Cao, Xiao-Yu; Wang, Jie-Yu; Pei, Jian

2014-03-12

A straightforward strategy has been used to construct large BN-embedded π-systems simply from azaacenes. BN heterosuperbenzene derivatives, the largest BN heteroaromatics to date, have been synthesized in three steps. The molecules exhibit curved π-surfaces, showing two different conformations which are self-organized into a sandwich structure and further packed into a π-stacking column. The assembled microribbons exhibit good charge transport properties and photoconductivity, representing an important step toward the optoelectronic applications of BN-embedded aromatics.

Pnma-BN: Another Boron Nitride Polymorph with Interesting Physical Properties

PubMed Central

Ma, Zhenyang; Han, Zheng; Liu, Xuhong; Yu, Xinhai; Wang, Dayun; Tian, Yi

2016-01-01

Structural, mechanical, electronic properties, and stability of boron nitride (BN) in Pnma structure were studied using first-principles calculations by Cambridge Serial Total Energy Package (CASTEP) plane-wave code, and the calculations were performed with the local density approximation and generalized gradient approximation in the form of Perdew–Burke–Ernzerhof. This BN, called Pnma-BN, contains four boron atoms and four nitrogen atoms buckled through sp3-hybridized bonds in an orthorhombic symmetry unit cell with Space group of Pnma. Pnma-BN is energetically stable, mechanically stable, and dynamically stable at ambient pressure and high pressure. The calculated Pugh ratio and Poisson’s ratio revealed that Pnma-BN is brittle, and Pnma-BN is found to turn brittle to ductile (~94 GPa) in this pressure range. It shows a higher mechanical anisotropy in Poisson’s ratio, shear modulus, Young’s modulus, and the universal elastic anisotropy index AU. Band structure calculations indicate that Pnma-BN is an insulator with indirect band gap of 7.18 eV. The most extraordinary thing is that the band gap increases first and then decreases with the increase of pressure from 0 to 60 GPa, and from 60 to 100 GPa, the band gap increases first and then decreases again. PMID:28336837

Hydrazinonicotinamide prolongs quantum dot circulation and reduces reticuloendothelial system clearance by suppressing opsonization and phagocyte engulfment

NASA Astrophysics Data System (ADS)

Jung, Kyung-Ho; Park, Jin Won; Paik, Jin-Young; Lee, Eun Jeong; Choe, Yearn Seong; Lee, Kyung-Han

2012-12-01

In this study, we investigated the effects of hydrazinonicotinamide (HYNIC)—a bifunctional crosslinker widely used to 99mTc radiolabel protein and nanoparticles for imaging studies—on quantum dot opsonization, macrophage engulfment and in vivo kinetics. In streptavidin-coated quantum dots (SA-QDots), conjugation with HYNIC increased the net negative charge without affecting the zeta potential. Confocal microscopy and fluorescence-activated cell sorting showed HYNIC attachment to suppress SA-QDot engulfment by macrophages. Furthermore, HYNIC conjugation suppressed surface opsonization by serum protein including IgG. When intravenously injected into mice, HYNIC conjugation significantly prolonged the circulation of SA-QDots and reduced their hepatosplenic uptake. Diminished reticuloendothelial system clearance of SA-QDots and aminoPEG-QDots by HYNIC conjugation was also demonstrated by in vivo and ex vivo optical imaging. The effects of HYNIC on the opsonization, phagocytosis and in vivo kinetics of quantum dots were reversed by removal of the hydrazine component from HYNIC. Thus, surface functionalization with HYNIC can improve the in vivo kinetics of quantum dots by reducing phagocytosis via suppression of surface opsonization.

Peptide (Lys-Leu) and amino acids (Lys and Leu) supplementations improve physiological activity and fermentation performance of brewer's yeast during very high-gravity (VHG) wort fermentation.

PubMed

Yang, Huirong; Zong, Xuyan; Cui, Chun; Mu, Lixia; Zhao, Haifeng

2017-12-22

Lys and Leu were generally considered as the key amino acids for brewer's yeast during beer brewing. In the present study, peptide Lys-Leu and a free amino acid (FAA) mixture of Lys and Leu (Lys + Leu) were supplemented in 24 °P wort to examine their effects on physiological activity and fermentation performance of brewer's yeast during very high-gravity (VHG) wort fermentation. Results showed that although both peptide Lys-Leu and their FAA mixture supplementations could increase the growth and viability, intracellular trehalose and glycerol content, wort fermentability, and ethanol content for brewer's yeast during VHG wort fermentation, and peptide was better than their FAA mixture at promoting growth and fermentation for brewer's yeast when the same dose was kept. Moreover, peptide Lys-Leu supplementation significantly increased the assimilation of Asp, but decreased the assimilation of Gly, Ala, Val, (Cys)2, Ile, Leu, Tyr, Phe, Lys, Arg, and Pro. However, the FAA mixture supplementation only promoted the assimilation of Lys and Leu, while reduced the absorption of total amino acids to a greater extent. Thus, the peptide Lys-Leu was more effective than their FAA mixture on the improvement of physiological activity, fermentation performance, and nitrogen metabolism of brewer's yeast during VHG wort fermentation. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

Chemically stabilized epitaxial wurtzite-BN thin film

NASA Astrophysics Data System (ADS)

Vishal, Badri; Singh, Rajendra; Chaturvedi, Abhishek; Sharma, Ankit; Sreedhara, M. B.; Sahu, Rajib; Bhat, Usha; Ramamurty, Upadrasta; Datta, Ranjan

2018-03-01

We report on the chemically stabilized epitaxial w-BN thin film grown on c-plane sapphire by pulsed laser deposition under slow kinetic condition. Traces of no other allotropes such as cubic (c) or hexagonal (h) BN phases are present. Sapphire substrate plays a significant role in stabilizing the metastable w-BN from h-BN target under unusual PLD growth condition involving low temperature and pressure and is explained based on density functional theory calculation. The hardness and the elastic modulus of the w-BN film are 37 & 339 GPa, respectively measured by indentation along <0001> direction. The results are extremely promising in advancing the microelectronic and mechanical tooling industry.

Crystal Structures of Lys-63-linked tri- and di-ubiquitin Reveal a Highly Extended Chain Architecture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weeks, S.; Grasty, K; Hernandez-Cuebas, L

2009-01-01

The covalent attachment of different types of poly-ubiquitin chains signal different outcomes for the proteins so targeted. For example, a protein modified with Lys-48-linked poly-ubiquitin chains is targeted for proteasomal degradation, whereas Lys-63-linked chains encode nondegradative signals. The structural features that enable these different types of chains to encode different signals have not yet been fully elucidated. We report here the X-ray crystal structures of Lys-63-linked tri- and di-ubiquitin at resolutions of 2.3 and 1.9 {angstrom}, respectively. The tri- and di-ubiquitin species adopt essentially identical structures. In both instances, the ubiquitin chain assumes a highly extended conformation with a left-handedmore » helical twist; the helical chain contains four ubiquitin monomers per turn and has a repeat length of {approx}110 {angstrom}. Interestingly, Lys-48 ubiquitin chains also adopt a left-handed helical structure with a similar repeat length. However, the Lys-63 architecture is much more open than that of Lys-48 chains and exposes much more of the ubiquitin surface for potential recognition events. These new crystal structures are consistent with the results of solution studies of Lys-63 chain conformation, and reveal the structural basis for differential recognition of Lys-63 versus Lys-48 chains.« less

Enzymatic characterization of a class II lysyl-tRNA synthetase, LysS, from Myxococcus xanthus.

PubMed

Oka, Manami; Takegawa, Kaoru; Kimura, Yoshio

2015-08-01

Lysyl-tRNA synthetases efficiently produce diadenosine tetraphosphate (Ap4A) from lysyl-AMP with ATP in the absence of tRNA. We characterized recombinant class II lysyl-tRNA synthetase (LysS) from Myxococcus xanthus and found that it is monomeric and requires Mn(2+) for the synthesis of Ap4A. Surprisingly, Zn(2+) inhibited enzyme activity in the presence of Mn(2+). When incubated with ATP, Mn(2+), lysine, and inorganic pyrophosphatase, LysS first produced Ap4A and ADP, then converted Ap4A to diadenosine triphosphate (Ap3A), and finally converted Ap3A to ADP, the end product of the reaction. Recombinant LysS retained Ap4A synthase activity without lysine addition. Additionally, when incubated with Ap4A (minus pyrophosphatase), LysS converted Ap4A mainly ATP and AMP, or ADP in the presence or absence of lysine, respectively. These results demonstrate that M. xanthus LysS has different enzymatic properties from class II lysyl-tRNA synthetases previously reported. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of a novel Arg-Gly-Asp-conjugated α-melanocyte stimulating hormone hybrid peptide for potential melanoma therapy.

PubMed

Yang, Jianquan; Guo, Haixun; Gallazzi, Fabio; Berwick, Marianne; Padilla, R Steven; Miao, Yubin

2009-08-19

The purpose of this study was to determine whether Arg-Gly-Asp (RGD)-conjugated α-melanocyte stimulating hormone (α-MSH) hybrid peptide could be employed to target melanocortin-1 (MC1) receptor for potential melanoma therapy. The RGD motif {cyclic(Arg-Gly-Asp-DTyr-Asp)} was coupled to [Cys(3,4,10), DPhe(7), Arg(11)]α-MSH(3-13) {(Arg(11))CCMSH} to generate RGD-Lys-(Arg(11))CCMSH hybrid peptide. The MC1 receptor binding affinity of RGD-Lys-(Arg(11))CCMSH was determined in B16/F1 melanoma cells. The internalization and efflux, melanoma targeting and pharmacokinetic properties and single photon emission computed tomography/CT (SPECT/CT) imaging of (99m)Tc-RGD-Lys-(Arg(11))CCMSH were determined in B16/F1 melanoma cells and melanoma-bearing C57 mice. Clonogenic cytotoxic effect of RGD-Lys-(Arg(11))CCMSH was examined in B16/F1 melanoma cells. RGD-Lys-(Arg(11))CCMSH displayed 2.1 nM MC1 receptor binding affinity. (99m)Tc-RGD-Lys-(Arg(11))CCMSH showed rapid internalization and extended retention in B16/F1 cells. The cellular uptake of (99m)Tc-RGD-Lys-(Arg(11))CCMSH was MC1 receptor-mediated. (99m)Tc-RGD-Lys-(Arg(11))CCMSH exhibited high tumor uptake (14.83 ± 2.94% ID/g 2 h postinjection) and prolonged tumor retention (7.59 ± 2.04% ID/g 24 h postinjection) in B16/F1 melanoma-bearing mice. Nontarget organ uptakes were generally low except for the kidneys. Whole-body clearance of (99m)Tc-RGD-Lys-(Arg(11))CCMSH was rapid, with approximately 62% of the injected radioactivity cleared through the urinary system by 2 h postinjection. Flank melanoma tumors were clearly imaged by small animal SPECT/CT using (99m)Tc-RGD-Lys-(Arg(11))CCMSH as an imaging probe 2 h postinjection. Single treatment (3 h incubation) with 100 nM of RGD-Lys-(Arg(11))CCMSH significantly (p < 0.05) decreased the clonogenic survival of B16/F1 cells by 65% compared to the untreated control cells. Favorable melanoma targeting property of (99m)Tc-RGD-Lys-(Arg(11))CCMSH and remarkable cytotoxic effect of RGD-Lys

Creep/Stress Rupture Behavior of 3D Woven SiC/SiC Composites with Sylramic-iBN, Super Sylramic-iBN and Hi-Nicalon-S Fibers at 2700F in Air

NASA Technical Reports Server (NTRS)

Bhatt, R. T.

2017-01-01

To determine the influence of fiber types on creep durability, 3D SiC/SiC CMCs were fabricated with Sylramic-iBN, super Sylramic-iBN and Hi-Nicalon-S fibers and the composite specimens were then tested under isothermal tensile creep at 14820C at 69, 103 and 138 MPa for up to 300hrs in air. The failed specimens were examined by scanning electron microscopy (SEM) and computed tomography (CT) for fracture mode analysis. The creep data of these composites are compared with those of other SiC/SiC composites in the literature. The results of this study will be presented.

Mechanical Properties and Plasma Erosion Resistance of ZrO2p(3Y)/BN-SiO2 Ceramic Composites under Different Sintering Temperature

NASA Astrophysics Data System (ADS)

Zhou, Yu; Duan1, Xiaoming; Jia, Dechang; Yang, Zhihua; Meng, Qingchang; Yu, Yang; Yu, Daren; Ding, Yongjie

2011-10-01

ZrO2p(3Y)/BN-SiO2 ceramic composites were hot pressed under different sintering temperature. The ceramic composites were composed by BN, m-ZrO2, t-ZrO2 and SiO2. The relative density, bending strength, elastic modulus and fracture toughness increase with the sintering temperature increasing, the maximum value of which at the sintering temperature of 1800°C are 97.5%, 229.9MPa, 60.8GPa and 3.55MPam1/2, respectively. The erosion resistance ability of ZrO2p(3Y)/BN-SiO2 ceramic composites rise gradually with the sintering temperature increasing, and the erosion rate of the ceramic composite sintered at 1800°C is 8.03×10-3mm/h.

An improved radiolabelled RNA aptamer molecule for HER2 imaging in cancers.

PubMed

Varmira, Kambiz; Hosseinimehr, Seyed Jalal; Noaparast, Zohreh; Abedi, Seyed Mohammad

2014-02-01

Human epidermal growth factor receptor 2 (HER2) expression has been shown to be increased in several types of human tumours. In this study, for the imaging of HER2-related tumours, a modified RNA aptamer with HER2-specific targeting was labelled with (99m)Tc, by using hydrazino nicotinamide (HYNIC) as the chelator in the presence of tricine or ethylenediamine-N,N'-diacetic acid (EDDA) as the co-ligand. Stability testing of the radiolabelled aptamers in the serum was performed through SDS-PAGE. The aptamer-radionuclide conjugate was evaluated for its cellular HER2-specific binding in ovarian cancer cells (SKOV-3), and its biodistribution properties were assessed in normal and SKOV-3 tumour-bearing mice. In the presence of either tricine or EDDA, the HYNIC-RNA aptamers were labelled with (99m)Tc at a high yield and radiochemical purity. Cellular experiments confirmed the specific binding of the RNA aptamer to the HER2 receptor. In the animal biodistribution study, uptake of the EDDA-co-liganded (99m)Tc-HYNIC-RNA aptamer by the liver and spleen was remarkably lower than that of the aptamer with tricine. Tumours also showed a higher accumulation of radioactivity with the EDDA-co-liganded aptamer complex. This study demonstrated EDDA to be better than tricine for use as a co-ligand with the RNA aptamer, which can be a potential tool for the molecular imaging of HER2-overexpressing cancers.

Development of a Novel SPECT Tracer to Image c-Met Expression in Non-Small Cell Lung Cancer in a Human Tumor Xenograft.

PubMed

Han, Zhaoguo; Xiao, Yadi; Wang, Kai; Yan, Ji; Xiao, Zunyu; Fang, Fang; Jin, Zhongnan; Liu, Yang; Sun, Xilin; Shen, Baozhong

2018-05-18

Rationale: Elevated expression of the c-Met receptor plays a crucial role in cancers. In non-small cell lung cancer (NSCLC), aberrant activation of c-Met signaling pathway contributes to tumorigenesis and cancer progression, and may mediate acquired resistance to epidermal growth factor receptor-targeted therapy. c-Met is therefore emerging as a promising therapeutic target for treating NSCLC, and the methods for noninvasive in vivo assessment of c-Met expression will improve NSCLC treatment and diagnosis. Methods: A new peptide-based (cMBP) radiotracer targeting c-Met, 99m Tc-hydrazine nicotinamide (HYNIC)-cMBP, was developed for single photon emission computed tomography (SPECT) imaging. Cell uptake assays were performed on two NSCLC cell lines with different c-Met expression: H1993 (high expression) and H1299 (no expression). In vivo tumor specificity was assessed by SPECT imaging in tumor-bearing mice at 0.5, 1, 2 and 4 h after injection of the probe. Blocking assays, biodistribution and autoradiography were also conducted to determine probe specificity. Results: 99m Tc-HYNIC-cMBP was prepared with high efficiency and showed higher uptake in H1993 cells than H1299 cells. Biodistribution and autoradiography also showed significantly higher accumulation of 99m Tc-HYNIC-cMBP in H1993 tumors than H1299 (H1993: 4.74±1.43 %ID/g and H1299: 1.00±0.37 %ID/g at 0.5h, p<0.05). H1993 tumors were clearly visualized at 0.5h in SPECT images, whereas H1299 tumors were not observed at any time. Specificity of 99m Tc-HYNIC-cMBP to c-Met was demonstrated by competitive block with excess un-radiolabeled peptide. Conclusion: We developed a novel SPECT tracer, 99m Tc-HYNIC-cMBP, for c-Met-targeted imaging in NSCLC that specifically bound to c-Met with favorable pharmacokinetics in vitro and in vivo. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Ultrahard stitching of nanotwinned diamond and cubic boron nitride in C 2-BN composite

DOE PAGES

Liu, Xiaobing; Chen, Xin; Ma, Hong-An; ...

2016-07-27

Materials combining the hardness and strength of diamond with the higher thermal stability of cubic boron nitride (cBN) have broad potential value in science and engineering. Reacting nanodiamond with cBN at moderate pressures and high temperatures provides a pathway to such materials. Here we report the fabrication of C x-BN nanocomposites, measuring up to 10 mm in longest dimension, by reacting nanodiamond with pre-synthesized cBN in a large-volume press. The nanocomposites consist of randomly-oriented diamond and cBN domains stitched together by sp 3-hybridized C-B and C-N bonds, leading to p-type semiconductivity. Dislocations near the sutures accommodate lattice mismatch between diamondmore » and cBN. Nanotwinning within both diamond and cBN domains further contributes to a bulk hardness ~50% higher than sintered cBN. We find the nanocomposite of C 2-BN exhibits p-type semiconductivity with low activation energy and high thermal stability, making it a functional,ultrahard substance.« less

Preclinical evaluation of 99mTc(CO)3-aspartic-N-monoacetic acid, 99mTc(CO)3(ASMA), a new renal radiotracer with pharmacokinetic properties comparable to 131I-OIH

PubMed Central

Lipowska, Malgorzata; Klenc, Jeffrey; Marzilli, Luigi G.; Taylor, Andrew T.

2014-01-01

In an ongoing effort to develop a renal tracer with pharmacokinetic properties comparable to PAH and superior to those of both 99mTc-MAG3 and 131I-OIH, we evaluated a new renal tricarbonyl radiotracer based on the aspartic-N-monoacetic acid ligand, 99mTc(CO)3(ASMA). The ASMA ligand features two carboxyl groups and an amine function for the coordination of the {99mTc(CO)3}+ core as well as a dangling carboxylate to facilitate rapid renal clearance. Methods rac-ASMA and L-ASMA were labeled with a 99mTc-tricarbonyl precursor and radiochemical purity of the labeled products was determined by HPLC. Using 131I-OIH as an internal control, we evaluated biodistribution in normal rats with 99mTc(CO)3(ASMA) isomers and in rats with renal pedicle ligation with 99mTc(CO)3(rac-ASMA). Clearance studies were conducted in 4 additional rats. In vitro radiotracer stability was determined in PBS buffer pH 7.4 and in challenge studies with cysteine and histidine. 99mTc(CO)3(ASMA) metabolites in urine were analyzed by HPLC. Results Both 99mTc(CO)3(ASMA) preparations had > 99% radiochemical purity and were stable in PBS buffer pH 7.4 for 24 h. Challenge studies on both revealed no significant displacement of the ligand. In normal rats, % injected dose in urine at 10 and 60 min for both preparations averaged 103% and 106% that of 131I-OIH, respectively. The renal clearances of 99mTc(CO)3(rac-ASMA) and 131I-OIH were comparable (P = 0.48). The tracer was excreted unchanged in the urine, proving its in vivo stability. In pedicle-ligated rats, 99mTc(CO)3(rac-ASMA) had less excretion into the bowel (P < 0.05) and was better retained in the blood (P < 0.05) than 131I-OIH. Conclusion Both 99mTc(CO)3(ASMA) complexes have pharmacokinetic properties in rats comparable to or superior to those of 131I-OIH, and human studies are warranted for their further evaluation. PMID:22717977

Enhancement of surface mechanical properties by using TiN[BCN/BN] n/c-BN multilayer system

NASA Astrophysics Data System (ADS)

Moreno, H.; Caicedo, J. C.; Amaya, C.; Muñoz-Saldaña, J.; Yate, L.; Esteve, J.; Prieto, P.

2010-11-01

The aim of this work is to improve the mechanical properties of AISI 4140 steel substrates by using a TiN[BCN/BN] n/c-BN multilayer system as a protective coating. TiN[BCN/BN] n/c-BN multilayered coatings via reactive r.f. magnetron sputtering technique were grown, systematically varying the length period ( Λ) and the number of bilayers ( n) because one bilayer ( n = 1) represents two different layers ( tBCN + tBN), thus the total thickness of the coating and all other growth parameters were maintained constant. The coatings were characterized by Fourier transform infrared spectroscopy showing bands associated with h-BN bonds and c-BN stretching vibrations centered at 1400 cm -1 and 1100 cm -1, respectively. Coating composition and multilayer modulation were studied via secondary ion mass spectroscopy. Atomic force microscopy analysis revealed a reduction in grain size and roughness when the bilayer number ( n) increased and the bilayer period decreased. Finally, enhancement of mechanical properties was determined via nanoindentation measurements. The best behavior was obtained when the bilayer period ( Λ) was 80 nm ( n = 25), yielding the relative highest hardness (˜30 GPa) and elastic modulus (230 GPa). The values for the hardness and elastic modulus are 1.5 and 1.7 times greater than the coating with n = 1, respectively. The enhancement effects in multilayered coatings could be attributed to different mechanisms for layer formation with nanometric thickness due to the Hall-Petch effect; because this effect, originally used to explain increased hardness with decreasing grain size in bulk polycrystalline metals, has also been used to explain hardness enhancements in multilayered coatings taking into account the thickness reduction at individual single layers that make up the multilayered system. The Hall-Petch model based on dislocation motion within layered and across layer interfaces has been successfully applied to multilayered coatings to explain this

Tunable localized surface plasmon resonances in one-dimensional h-BN/graphene/h-BN quantum-well structure

NASA Astrophysics Data System (ADS)

Kaibiao, Zhang; Hong, Zhang; Xinlu, Cheng

2016-03-01

The graphene/hexagonal boron-nitride (h-BN) hybrid structure has emerged to extend the performance of graphene-based devices. Here, we investigate the tunable plasmon in one-dimensional h-BN/graphene/h-BN quantum-well structures. The analysis of optical response and field enhancement demonstrates that these systems exhibit a distinct quantum confinement effect for the collective oscillations. The intensity and frequency of the plasmon can be controlled by the barrier width and electrical doping. Moreover, the electron doping and the hole doping lead to very different results due to the asymmetric energy band. This graphene/h-BN hybrid structure may pave the way for future optoelectronic devices. Project supported by the National Natural Science Foundation of China (Grant Nos. 11474207 and 11374217) and the Scientific Research Fund of Sichuan University of Science and Engineering, China (Grant No. 2014PY07).

Purification and characterization of the bacteriocin Thuricin Bn1 produced by Bacillus thuringiensis subsp. kurstaki Bn1 isolated from a hazelnut pest.

PubMed

Ugras, Serpil; Sezen, Kazim; Kati, Hatice; Demirbag, Zihni

2013-02-01

A novel bioactive molecule produced by Bacillus thuringiensis subsp. kurstaki Bn1 (Bt-Bn1), isolated from a common pest of hazelnut, Balaninus nucum L. (Coleoptera: Curculionidae), was determined, purified, and characterized in this study. The Bt-Bn1 strain was investigated for antibacterial activity with an agar spot assay and well diffusion assay against B. cereus, B. weinhenstephenensis, L. monocytogenes, P. savastanoi, P. syringae, P. lemoignei, and many other B. thuringiensis strains. The production of bioactive molecule was determined at the early logarithmic phase in the growth cycle of strain Bt-Bn1 and its production continued until the beginning of the stationary phase. The mode of action of this molecule displayed bacteriocidal or bacteriolytic effect depending on the concentration. The bioactive molecule was purified 78-fold from the bacteria supernatant with ammonium sulfate precipitation, dialysis, ultrafiltration, gel filtration chromatography, and HPLC, respectively. The molecular mass of this molecule was estimated via SDS-PAGE and confirmed by the ESI-TOFMS as 3,139 Da. The bioactive molecule was also determined to be a heat-stable, pH-stable (range 6-8), and proteinase K sensitive antibacterial peptide, similar to bacteriocins. Based on all characteristics determined in this study, the purified bacteriocin was named as thuricin Bn1 because of the similarities to the previously identified thuricin-like bacteriocin produced by the various B. thuringiensis strains. Plasmid elution studies showed that gene responsible for the production of thuricin Bn1 is located on the chromosome of Bt-Bn1. Therefore, it is a novel bacteriocin and the first recorded one produced by an insect originated bacterium. It has potential usage for the control of many different pathogenic and spoilage bacteria in the food industry, agriculture, and various other areas.

One-Shot Multiple Borylation toward BN-Doped Nanographenes.

PubMed

Matsui, Kohei; Oda, Susumu; Yoshiura, Kazuki; Nakajima, Kiichi; Yasuda, Nobuhiro; Hatakeyama, Takuji

2018-01-31

One-shot double, triple, and quadruple borylation reactions of triarylamines were developed through a judicious choice of boron source and Brønsted base. With the aid of borylation reactions, a variety of BN-doped nanographenes were synthesized in two steps from commercially available starting materials. An organic light-emitting diode device employing BN-doped nanographene as an emitter exhibited deep pure-blue emission at 460 nm, with CIE coordinates of (0.13, 0.11), and an external quantum efficiency of 18.3%.

Micrometric BN powders used as catalyst support: influence of the precursor on the properties of the BN ceramic

NASA Astrophysics Data System (ADS)

Perdigon-Melon, José Antonio; Auroux, Aline; Guimon, Claude; Bonnetot, Bernard

2004-02-01

Thin powders and foams of boron nitride have been prepared from molecular precursors for use as noble metal supports in the catalytic conversion of methane. Different precursors originating from borazines have been tested. The best results were obtained using a precursor derived from trichloroborazine (TCB) which, after reacting with ammonia at room temperature and then thermolyzing up to 1800°C, led to BN powders with a specific area of more than 300 m 2 g -1 and a micrometric spherical texture. Comparable results were obtained using polyborazylene under similar conditions. Aminoborazine-derived precursors did not yield such high specific area ceramics but the BN microstructure resembled a foam with a crystallized skin and amorphous internal part. These differences were related to the chemical mechanism of the conversion of the precursor into BN. Polyhaloborazines and polyborazines yielded BN through gas-solid reactions whereas aminoborazine polymers could be kept waxy up to high temperatures, which favored the glassy foam. Catalysts composed of BN support and platinum have been prepared using two routes: from a mixture of precursor or by impregnation of a BN powder leading to very different catalysts.

I-V characteristics of graphene nanoribbon/h-BN heterojunctions and resonant tunneling.

PubMed

Wakai, Taiga; Sakamoto, Shoichi; Tomiya, Mitsuyoshi

2018-07-04

We present the first principle calculations of the electrical properties of graphene sheet/h-BN heterojunction (GS/h-BN) and 11-armchair graphene nanoribbon/h-BN heterojunction (11-AGNR/h-BN), which are carried out using the density functional theory (DFT) method and the non-equilibrium Green's function (NEGF) technique. Since 11-AGNR belongs to the conductive (3n-1)-family of AGNR, both are metallic nanomaterials with two transverse arrays of h-BN, which is a wide-gap semi-conductor. The two h-BN arrays act as double barriers. The transmission functions (TF) and I-[Formula: see text] characteristics of GS/h-BN and 11-AGNR/h-BN are calculated by DFT and NEGF, and they show that quantum double barrier tunneling occurs. The TF becomes very spiky in both materials, and it leads to step-wise I-[Formula: see text] characteristics rather than negative resistance, which is the typical behavior of double barriers in semiconductors. The results of our first principle calculations are also compared with 1D Dirac equation model for the double barrier system. The model explains most of the peaks of the transmission functions nearby the Fermi energy quite well. They are due to quantum tunneling.

99mTc: Labeling Chemistry and Labeled Compounds

NASA Astrophysics Data System (ADS)

Alberto, R.; Abram, U.

This chapter reviews the radiopharmaceutical chemistry of technetium related to the synthesis of perfusion agents and to the labeling of receptor-binding biomolecules. To understand the limitations of technetium chemistry imposed by future application of the complexes in nuclear medicine, an introductory section analyzes the compulsory requirements to be considered when facing the incentive of introducing a novel radiopharmaceutical into the market. Requirements from chemistry, routine application, and market are discussed. In a subsequent section, commercially available 99mTc-based radiopharmaceuticals are treated. It covers the complexes in use for imaging the most important target organs such as heart, brain, or kidney. The commercially available radiopharmaceuticals fulfill the requirements outlined earlier and are discussed with this background. In a following section, the properties and perspectives of the different generations of radiopharmaceuticals are described in a general way, covering characteristics for perfusion agents and for receptor-specific molecules. Technetium chemistry for the synthesis of perfusion agents and the different labeling approaches for target-specific biomolecules are summarized. The review comprises a general introduction to the common approaches currently in use, employing the N x S4-x , [3+1] and 2-hydrazino-nicotinicacid (HYNIC) method as well as more recent strategies such as the carbonyl and the TcN approach. Direct labeling without the need of a bifunctional chelator is briefly reviewed as well. More particularly, recent developments in the labeling of concrete targeting molecules, the second generation of radiopharmaceuticals, is then discussed and prominent examples with antibodies/peptides, neuroreceptor targeting small molecules, myocardial imaging agents, vitamins, thymidine, and complexes relevant to multidrug resistance are given. In addition, a new approach toward peptide drug development is described. The section

Conserved Residues Lys57 and Lys401 of Protein Disulfide Isomerase Maintain an Active Site Conformation for Optimal Activity: Implications for Post-Translational Regulation

PubMed Central

Caba, Cody; Ali Khan, Hyder; Auld, Janeen; Ushioda, Ryo; Araki, Kazutaka; Nagata, Kazuhiro; Mutus, Bulent

2018-01-01

Despite its study since the 1960's, very little is known about the post-translational regulation of the multiple catalytic activities performed by protein disulfide isomerase (PDI), the primary protein folding catalyst of the cell. This work identifies a functional role for the highly conserved CxxC-flanking residues Lys57 and Lys401 of human PDI in vitro. Mutagenesis studies have revealed these residues as modulating the oxidoreductase activity of PDI in a pH-dependent manner. Non-conservative amino acid substitutions resulted in enzyme variants upwards of 7-fold less efficient. This attenuated activity was found to translate into a 2-fold reduction of the rate of electron shuttling between PDI and the intraluminal endoplasmic reticulum oxidase, ERO1α, suggesting a functional significance to oxidative protein folding. In light of this, the possibility of lysine acetylation at residues Lys57 and Lys401 was assessed by in vitro treatment using acetylsalicylic acid (aspirin). A total of 28 acetyllysine residues were identified, including acLys57 and acLys401. The kinetic behavior of the acetylated protein form nearly mimicked that obtained with a K57/401Q double substitution variant providing an indication that acetylation of the active site-flanking lysine residues can act to reversibly modulate PDI activity. PMID:29541639

Physical, mechanical and neutron shielding properties of h-BN/Gd2O3/HDPE ternary nanocomposites

NASA Astrophysics Data System (ADS)

İrim, Ş. Gözde; Wis, Abdulmounem Alchekh; Keskin, M. Aker; Baykara, Oktay; Ozkoc, Guralp; Avcı, Ahmet; Doğru, Mahmut; Karakoç, Mesut

2018-03-01

In order to prepare an effective neutron shielding material, not only neutron but also gamma absorption must be taken into account. In this research, a polymer nanocomposite based novel type of multifunctional neutron shielding material is designed and fabricated. For this purpose, high density polyethylene (HDPE) was compounded with different amounts of hexagonal boron nitride (h-BN) and Gd2O3 nanoparticles having average particle size of 100 nm using melt-compounding technique. The mechanical, thermal and morphological properties of nanocomposites were investigated. As filler content increased, the absorption of both neutron and gamma fluxes increased despite fluctuating neutron absorption curves. Adding h-BN and Gd2O3 nano particles had a significant influence on both neutron and gamma attenuation properties (Σ, cm-1 and μ/ρ, cm-2/g) of ternary shields and they show an enhancement of 200-280%, 14-52% for neutron and gamma radiations, respectively, in shielding performance.

Computational Prediction of the Protonation Sites of Ac-Lys-(Ala)n-Lys-NH2 Peptides through Conceptual DFT Descriptors.

PubMed

Sastre, Sebastián; Frau, Juan; Glossman-Mitnik, Daniel

2017-03-13

Six density functionals (M11, M11L, MN12L, MN12SX, N12, and N12SX) in connection with the Def2TZVP basis set and the SMD solvation model (water as a solvent) have been assessed for the calculation of the molecular structure and properties of several peptides with the general formulaAc-Lys-(Ala)n-Lys-NH2,withn=0to5  [...].

Yeast Derived LysA2 Can Control Bacterial Contamination in Ethanol Fermentation.

PubMed

Kim, Jun-Seob; Daum, M Angela; Jin, Yong-Su; Miller, Michael J

2018-05-24

Contamination of fuel-ethanol fermentations continues to be a significant problem for the corn and sugarcane-based ethanol industries. In particular, members of the Lactobacillaceae family are the primary bacteria of concern. Currently, antibiotics and acid washing are two major means of controlling contaminants. However, antibiotic use could lead to increased antibiotic resistance, and the acid wash step stresses the fermenting yeast and has limited effectiveness. Bacteriophage endolysins such as LysA2 are lytic enzymes with the potential to contribute as antimicrobials to the fuel ethanol industries. Our goal was to evaluate the potential of yeast-derived LysA2 as a means of controlling Lactobacillaceae contamination. LysA2 intracellularly produced by Pichia pastoris showed activity comparable to Escherichia coli produced LysA2. Lactic Acid Bacteria (LAB) with the A4α peptidoglycan chemotype (L-Lys-D-Asp crosslinkage) were the most sensitive to LysA2, though a few from that chemotype were insensitive. Pichia -expressed LysA2, both secreted and intracellularly produced, successfully improved ethanol productivity and yields in glucose (YPD60) and sucrose-based (sugarcane juice) ethanol fermentations in the presence of a LysA2 susceptible LAB contaminant. LysA2 secreting Sacharomyces cerevisiae did not notably improve production in sugarcane juice, but it did control bacterial contamination during fermentation in YPD60. Secretion of LysA2 by the fermenting yeast, or adding it in purified form, are promising alternative tools to control LAB contamination during ethanol fermentation. Endolysins with much broader lytic spectrums than LysA2 could supplement or replace the currently used antibiotics or the acidic wash.

A bioinformatics-based overview of protein Lys-Ne-acetylation

USDA-ARS?s Scientific Manuscript database

Among posttranslational modifications, there are some conceptual similarities between Lys-N'-acetylation and Ser/Thr/Tyr O-phosphorylation. Herein we present a bioinformatics-based overview of reversible protein Lys-acetylation, including some comparisons with reversible protein phosphorylation. T...

Augmenter of liver regeneration attenuates acute rejection after rat liver transplantation.

PubMed

Chen, Yong; Liang, Shaoyong; Long, Feiwu; Li, Jinzheng; Gong, Jianping

2016-07-01

The role of augmenter of liver regeneration (ALR) on liver transplantation immune regulation remains unknown. Male Lewis and Brown-Norway (BN) rats were assigned to allograft group (Lewis-to-BN liver transplantation), isograft group (BN-to-BN), and ALR group (Lewis-to-BN, ALR, 100 μg/kg/d, intramuscular injection postoperatively). Rats were sacrificed at indicated times for assessment of cytokines production, T-cell (TC) activation and apoptosis. Kupffer cells (KCs) and TCs were isolated from grafts to assess cytokine expression. Effect of ALR and KCs on TCs was monitored by co-culture of (3)H-thymidine TCs. (1) Treatment with ALR significantly decreased interleukin-2 and interferon-γ expression, promoted TC apoptosis, and prolonged the survival of allografts; (2) KCs in ALR group and isograft group that had significantly increased interleukin-10 and decreased tumor necrosis factor-α expression were able to inhibit TC proliferation and induce their apoptosis relative to KCs in the allograft group; (3) ALR and KCs directly inhibited TC proliferation and activation and induced TC apoptosis. ALR could inhibit TC proliferation and function both in vivo and in vitro and attenuate acute rejection after liver transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhancing the mechanical properties of BN nanosheet-polymer composites by uniaxial drawing

NASA Astrophysics Data System (ADS)

Jan, Rahim; May, Peter; Bell, Alan P.; Habib, Amir; Khan, Umar; Coleman, Jonathan N.

2014-04-01

We have used liquid exfoliation of hexagonal Boron-Nitride (BN) to prepare composites of BN nanosheets of three different sizes in polyvinylchloride matrices. These composites show low levels of reinforcement, consistent with poor alignment of the nanosheets as-described by a modified version of Halpin-Tsai theory. However, drawing of the composites to 300% strain results in a considerable increase in mechanical properties with the maximum composite modulus and strength both ~×3 higher than that of the pristine polymer. In addition, the rate of increase of modulus with BN volume fraction was up to 3-fold larger than for the unstrained composites. This is higher than can be explained by drawing-induced alignment using Halpin-Tsai theory. However, the data was consistent with a combination of alignment and strain-induced de-aggregation of BN multilayers.

Enhancing the mechanical properties of BN nanosheet-polymer composites by uniaxial drawing.

PubMed

Jan, Rahim; May, Peter; Bell, Alan P; Habib, Amir; Khan, Umar; Coleman, Jonathan N

2014-05-07

We have used liquid exfoliation of hexagonal Boron-Nitride (BN) to prepare composites of BN nanosheets of three different sizes in polyvinylchloride matrices. These composites show low levels of reinforcement, consistent with poor alignment of the nanosheets as-described by a modified version of Halpin-Tsai theory. However, drawing of the composites to 300% strain results in a considerable increase in mechanical properties with the maximum composite modulus and strength both ∼×3 higher than that of the pristine polymer. In addition, the rate of increase of modulus with BN volume fraction was up to 3-fold larger than for the unstrained composites. This is higher than can be explained by drawing-induced alignment using Halpin-Tsai theory. However, the data was consistent with a combination of alignment and strain-induced de-aggregation of BN multilayers.

Anticorrosive performance of waterborne epoxy coatings containing water-dispersible hexagonal boron nitride (h-BN) nanosheets

NASA Astrophysics Data System (ADS)

Cui, Mingjun; Ren, Siming; Chen, Jia; Liu, Shuan; Zhang, Guangan; Zhao, Haichao; Wang, Liping; Xue, Qunji

2017-03-01

Homogenous dispersion of hexagonal boron nitride (h-BN) nanosheets in solvents or in the polymer matrix is crucial to initiate their many applications. Here, homogeneous dispersion of hexagonal boron nitride (h-BN) in epoxy matrix was achieved with a water-soluble carboxylated aniline trimer derivative (CAT-) as a dispersant, which was attributed to the strong π-π interaction between h-BN and CAT-, as proved by Raman and UV-vis spectra. Transmission electron microscopy (TEM) analysis confirmed a random dispersion of h-BN nanosheets in the waterborne epoxy coatings. The deterioration process of water-borne epoxy coating with and without h-BN nanosheets during the long-term immersion in 3.5 wt% NaCl solution was investigated by electrochemical measurements and water absorption test. Results implied that the introduction of well dispersed h-BN nanosheets into waterborne epoxy system remarkably improved the corrosion protection performance to substrate. Moreover, 1 wt% BN/EP composite coated substrate exhibited higher impedance modulus (1.3 × 106 Ω cm2) and lower water absorption (4%) than those of pure waterborne epoxy coating coated electrode after long-term immersion in 3.5 wt% NaCl solution, demonstrating its superior anticorrosive performance. This enhanced anticorrosive performance was mainly ascribed to the improved water barrier property of epoxy coating via incorporating homogeneously dispersed h-BN nanosheets.

TcNPR3 from Theobroma cacao functions as a repressor of the pathogen defense response

PubMed Central

2013-01-01

Background Arabidopsis thaliana (Arabidopsis) NON-EXPRESSOR OF PR1 (NPR1) is a transcription coactivator that plays a central role in regulating the transcriptional response to plant pathogens. Developing flowers of homozygous npr3 mutants are dramatically more resistant to infection by the pathogenic bacterium Pseudomonas syringae, suggesting a role of NPR3 as a repressor of NPR1-mediated defense response with a novel role in flower development. Results We report here the characterization of a putative NPR3 gene from the tropical tree species Theobroma cacao (TcNPR3). Like in Arabidopsis, TcNPR3 was constitutively expressed across a wide range of tissue types and developmental stages but with some differences in relative levels compared to Arabidopsis. To test the function of TcNPR3, we performed transgenic complementation analysis by introducing a constitutively expressing putative TcNPR3 transgene into an Arabidopsis npr3 mutant. TcNPR3 expressing Arabidopsis plants were partially restored to the WT pathogen phenotype (immature flowers susceptible to bacterial infection). To test TcNPR3 function directly in cacao tissues, a synthetic microRNA targeting TcNPR3 mRNA was transiently expressed in cacao leaves using an Agrobacterium-infiltration method. TcNPR3 knock down leaf tissues were dramatically more resistance to infection with Phytophthora capsici in a leaf bioassay, showing smaller lesion sizes and reduced pathogen replication. Conclusions We conclude that TcNPR3 functions similar to the Arabidopsis NPR3 gene in the regulation of the cacao defense response. Since TcNPR3 did not show a perfect complementation of the Arabidopsis NPR3 mutation, the possibility remains that other functions of TcNPR3 remain to be found. This novel knowledge can contribute to the breeding of resistant cacao varieties against pathogens through molecular markers based approaches or biotechnological strategies. PMID:24314063

TcNPR3 from Theobroma cacao functions as a repressor of the pathogen defense response.

PubMed

Shi, Zi; Zhang, Yufan; Maximova, Siela N; Guiltinan, Mark J

2013-12-06

Arabidopsis thaliana (Arabidopsis) NON-EXPRESSOR OF PR1 (NPR1) is a transcription coactivator that plays a central role in regulating the transcriptional response to plant pathogens. Developing flowers of homozygous npr3 mutants are dramatically more resistant to infection by the pathogenic bacterium Pseudomonas syringae, suggesting a role of NPR3 as a repressor of NPR1-mediated defense response with a novel role in flower development. We report here the characterization of a putative NPR3 gene from the tropical tree species Theobroma cacao (TcNPR3). Like in Arabidopsis, TcNPR3 was constitutively expressed across a wide range of tissue types and developmental stages but with some differences in relative levels compared to Arabidopsis. To test the function of TcNPR3, we performed transgenic complementation analysis by introducing a constitutively expressing putative TcNPR3 transgene into an Arabidopsis npr3 mutant. TcNPR3 expressing Arabidopsis plants were partially restored to the WT pathogen phenotype (immature flowers susceptible to bacterial infection). To test TcNPR3 function directly in cacao tissues, a synthetic microRNA targeting TcNPR3 mRNA was transiently expressed in cacao leaves using an Agrobacterium-infiltration method. TcNPR3 knock down leaf tissues were dramatically more resistance to infection with Phytophthora capsici in a leaf bioassay, showing smaller lesion sizes and reduced pathogen replication. We conclude that TcNPR3 functions similar to the Arabidopsis NPR3 gene in the regulation of the cacao defense response. Since TcNPR3 did not show a perfect complementation of the Arabidopsis NPR3 mutation, the possibility remains that other functions of TcNPR3 remain to be found. This novel knowledge can contribute to the breeding of resistant cacao varieties against pathogens through molecular markers based approaches or biotechnological strategies.

Effect of substrate temperature in the synthesis of BN nanostructures

NASA Astrophysics Data System (ADS)

Sajjad, M.; Zhang, H. X.; Peng, X. Y.; Feng, P. X.

2011-06-01

Boron nitride (BN) nanostructures were grown on molybdenum discs at different substrate temperatures using the short-pulse laser plasma deposition technique. Large numbers of randomly oriented nanorods of fiber-like structures were obtained. The variation in the length and diameter of the nanorods as a function of the substrate temperature was systematically studied. The surface morphologies of the samples were studied using scanning electron microscopy. Energy dispersive x-ray spectroscopy confirmed that both the elements boron and nitrogen are dominant in the nanostructure. The x-ray diffraction (XRD) technique was used to analyse BN phases. The XRD peak that appeared at 26° showed the presence of hexagonal BN phase, whereas the peak at 44° was related to cubic BN content in the samples. Raman spectroscopic analysis showed vibrational modes of sp2- and sp3-type bonding in the sample. The Raman spectra agreed well with XRD results.

In situ Spectroscopic Analysis and Quantification of [Tc(CO)3]+ in Hanford Tank Waste.

PubMed

Branch, Shirmir D; French, Amanda D; Lines, Amanda M; Soderquist, Chuck Z; Rapko, Brian M; Heineman, William R; Bryan, Samuel A

2018-06-12

The quantitative conversion of non-pertechnetate [Tc(CO)3]+ species in nuclear waste storage tank 241-AN-102 at the Hanford Site is demonstrated. A waste sample containing the [Tc(CO)3]+ species is added to a developer solution that rapidly converts the non-emissive species into a luminescent complex, which is detected spectroscopically. This method was first demonstrated using a [Tc(CO)3]+ sample non-waste containing matrix to determine a detection limit (LOD), resulting in a [Tc(CO)3]+ LOD of 2.20 × 10-7 M, very near the LOD of the independently synthesized standard (2.10 × 10-7 M). The method was then used to detect [Tc(CO)3]+ in a simulated waste using the standard addition method, resulting in a [Tc(CO)3]+ concentration of 1.89 × 10-5 M (within 27.7% of the concentration determined by β- liquid scintillation counting). Three samples from 241-AN-102 were tested by the standard addition method: (1) a 5 M Na adjusted fraction, (2) a fraction depleted of 137Cs, (3) and an acid-stripped eluate. The concentrations of [Tc(CO)3]+ in these fractions were determined to be 9.90 × 10-6 M (1), 0 M (2), and 2.46 × 10-6 M (3), respectively. The concentration of [Tc(CO)3]+ in the as-received AN-102 tank waste supernatant was determined to be 1.84 × 10-5 M.

Tandem UIMs confer Lys48 ubiquitin chain substrate preference to deubiquitinase USP25

PubMed Central

Kawaguchi, Kohei; Uo, Kazune; Tanaka, Toshiaki; Komada, Masayuki

2017-01-01

Ubiquitin-specific protease (USP) 25, belonging to the USP family of deubiquitinases, harbors two tandem ubiquitin-interacting motifs (UIMs), a ~20-amino-acid α-helical stretch that binds to ubiquitin. However, the role of the UIMs in USP25 remains unclear. Here we show that the tandem UIM region binds to Lys48-, but not Lys63-, linked ubiquitin chains, where the two UIMs played a critical and cooperative role. Purified USP25 exhibited higher ubiquitin isopeptidase activity to Lys48-, than to Lys63-, linked ubiquitin chains. Mutations that disrupted the ubiquitin-binding ability of the tandem UIMs resulted in a reduced ubiquitin isopeptidase activity of USP25, suggesting a role for the UIMs in exerting the full catalytic activity of USP25. Moreover, when mutations that convert the binding preference from Lys48- to Lys63-linked ubiquitin chains were introduced into the tandem UIM region, the USP25 mutants acquired elevated and reduced isopeptidase activity toward Lys63- and Lys48-linked ubiquitin chains, respectively. These results suggested that the binding preference of the tandem UIMs toward Lys48-linked ubiquitin chains contributes not only to the full catalytic activity but also to the ubiquitin chain substrate preference of USP25, possibly by selectively holding the Lys48-linked ubiquitin chain substrates in the proximity of the catalytic core. PMID:28327663

Antinociceptive potency of a fluorinated cyclopeptide Dmt-c[D-Lys-Phe-p-CF3-Phe-Asp]NH2.

PubMed

Piekielna-Ciesielska, Justyna; Mollica, Adriano; Pieretti, Stefano; Fichna, Jakub; Szymaszkiewicz, Agata; Zielińska, Marta; Kordek, Radzisław; Janecka, Anna

2018-12-01

Opioid peptides and opiate drugs such as morphine, mediate their analgesic effects, but also undesired side effects, mostly through activation of the mu opioid receptor. However, delta- and kappa-opioid receptors can also contribute to the analgesic effects of opioids. Recent findings showed that simultaneous activation of multiple opioid receptors may result in additional analgesia with fewer side effects. Here, we evaluated the pharmacological profile of our formerly developed mixed mu/kappa-opioid receptor ligands, Dmt-c[D-Lys-Phe-Phe-Asp]NH 2 (C-36) and Dmt-c[D-Lys-Phe-p-CF 3 -Phe-Asp]NH 2 (F-81). The ability of these peptides to cross the blood-brain barrier was tested in the parallel artificial membrane permeability (PAMPA) assay. On the basis of the hot-plate test in mice after central and peripheral administration, analog F-81 was selected for the anti-nociceptive and anti-inflammatory activity assessment after peripheral administration.

44Sc-DOTA-BN[2-14]NH2 in comparison to 68Ga-DOTA-BN[2-14]NH2 in pre-clinical investigation. Is 44Sc a potential radionuclide for PET?

PubMed

Koumarianou, E; Loktionova, N S; Fellner, M; Roesch, F; Thews, O; Pawlak, D; Archimandritis, S C; Mikolajczak, R

2012-12-01

In the present study we demonstrate the in vitro and in vivo comparison of the (44)Sc and (68)Ga labeled DOTA-BN[2-14]NH(2). (44)Sc is a positron emitter with a half life of 3.92 h. Hence it could be used for PET imaging with ligands requiring longer observation time than in the case of (68)Ga. The binding affinity of (nat)Sc-DOTA-BN[2-14]NH(2) and (nat)Ga-DOTA-BN[2-14]NH(2) to GRP receptors was studied in competition to [(125)I-Tyr(4)]-Bombesin in the human prostate cancer cell line PC-3. A preliminary biodistribution in normal rats was performed, while first microPET images were assessed in male Copenhagen rats bearing the androgen-independent Dunning R-3327-AT-1 prostate cancer tumor. The affinity to GRP receptors in the PC-3 cell line was higher for (nat)Ga-DOTA-BN[2-14]NH(2) (IC(50)(nM)=0.85 ± 0.06) than that of (nat)Sc-DOTA-BN[2-14]NH(2) (IC(50) (nM)=6.49 ± 0.13). The internalization rate of (68)Ga labeled DOTA-BN[2-14]NH(2) was slower than that of (44)Sc, but their final internalization percents were comparable. (68)Ga-DOTA-BN[2-14]NH(2) was externalized faster than (44)Sc-DOTA-BN[2-14]NH(2). The biodistribution of (44)Sc-DOTA-BN[2-14]NH(2) and (68)Ga-DOTA-BN[2-14]NH(2) in normal rats revealed a higher uptake in target organs and tissues of the first one while both excreted mainly through urinary tract. In microPET images both tracers were accumulated in the tumor with similar uptake patterns. Despite the differences in the receptor affinity both the (68)Ga- and the (44)Sc-labeled DOTA-BN[2-14]NH(2) tracers showed comparable distribution and similar time constants of uptake and elimination. Moreover no differences in tumor accumulation (neither in the overall uptake nor in the dynamics) were observed from the microPet imaging. From that perspective the use of either (44)Sc or (68)Ga for detecting tumors with GRP receptors is equivalent. Copyright © 2012 Elsevier Ltd. All rights reserved.

Somatostatin receptor imaging in non-(131)I-avid metastatic differentiated thyroid carcinoma for determining the feasibility of peptide receptor radionuclide therapy with (177)Lu-DOTATATE: low fraction of patients suitable for peptide receptor radionuclide therapy and evidence of chromogranin A level-positive neuroendocrine differentiation.

PubMed

Jois, Bhargavi; Asopa, Ramesh; Basu, Sandip

2014-06-01

The aim of the study was to evaluate somatostatin receptor expression in non-I-concentrating metastatic differentiated thyroid carcinoma by Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy and to determine the feasibility of Lu-DOTATATE (therapeutic analog) therapy in cases with positive Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy. In this research study, 19 patients diagnosed with differentiated thyroid carcinoma with non-iodine-concentrating metastasis with elevated serum thyroglobulin levels, attending thyroid outpatient department for follow-up, underwent Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scan for the evaluation of positivity of somatostatin receptor (SSTR). Based on the visual grading, SSTR-positive lesions were graded into 4 categories (grades I-IV) in comparison with the hepatic uptake on the scan. Patients with grades III and IV uptake in lesions (equal to or more than hepatic uptake on scan) were scheduled for Lu-DOTATATE administration. Posttherapy Lu-DOTATATE scan was undertaken during discharge from the isolation ward. Of the 19 patients studied, 12 patients (63%) showed SSTR-positive lesion expression demonstrating uptake ranging from grade I-IV, and 7 patients (37%) did not demonstrate any tracer uptake. On a lesion-specific analysis, of the total 57 metastatic lesions, 4 lesions (7%) demonstrated grade I tracer uptake, 18 lesions (31%) grade II (less than liver), 2 lesions (3.5%) grade III (equal to liver uptake), and 1 lesion showed grade IV uptake (more than liver). Interestingly, an elevated serum chromogranin A level was documented in 3 of the patients with grades III and IV tumor uptake. A comparison of Ga-DOTATATE PET-CT and Tc-HYNIC-TOC in 4 patients who underwent both the scans demonstrated no significant differences in the tracer concentration in the metastatic lesions in any of the patients on visual grading. Based on the criterion of high tracer uptake and the patient consent, finally 2 of 3 patients were treated with Lu-DOTATATE. On follow

The Phosphatidylinositol 3-kinase Class III Complex Containing TcVps15 and TcVps34 Participates in Autophagy in Trypanosoma cruzi.

PubMed

Schoijet, Alejandra C; Sternlieb, Tamara; Alonso, Guillermo D

2017-05-01

Autophagy is a degradative process by which eukaryotic cells digest their own components to provide aminoacids that may function as energy source under nutritional stress conditions. There is experimental evidence for autophagy in parasitic protists belonging to the family Trypanosomatidae. However, few proteins implicated in this process have been characterized so far in these parasites. Moreover, it has been shown that autophagy is involved in Trypanosoma cruzi differentiation and thus might have a role in pathogenicity. Here, we report the cloning and biochemical characterization of TcVps15. In addition, we demonstrate that TcVps15 interact with the PI3K TcVps34 and that both proteins associate with cellular membranes. Under nutritional stress conditions, TcVps15 and TcVps34 modify their subcellular distribution showing a partial co-localization in autophagosomes with TcAtg8.1 and using an active site TcVps15-mutated version (TcVps15-K219D-HA) we demonstrated that this relocalization depends on the TcVps15 catalytic activity. Overexpression of TcVps15-HA and TcVps15-K219D-HA also leads to increased accumulation of monodansylcadaverine (MDC) in autophagic vacuoles under nutritional stress conditions compared to wild-type cells. In addition, the MDC-specific activity shows to be significantly higher in TcVps15-HA overexpressing cells when compared with TcVps15-K219D-HA. Our results reveal for the first time a role of TcVps15 as a key regulator of TcVps34 enzymatic activity and implicate the TcVps15-Vps34 complex in autophagy in T. cruzi, exposing a new key pathway to explore novel chemotherapeutic targets. © 2016 The Author(s) Journal of Eukaryotic Microbiology © 2016 International Society of Protistologists.

APOA5 -1131T>C and APOC3 -455T>C polymorphisms are associated with an increased risk of coronary heart disease.

PubMed

Sun, Y; Zhou, R B; Chen, D M

2015-12-28

The aim of this study was to investigate correlations between apolipoprotein A-V (APOA5) -1131T>C and apolipoprotein C-III (APOC3) -455T>C polymorphisms and coronary heart disease (CHD). PubMed, Ovid, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang databases were searched using combinations of keywords relating to these polymorphisms and CHD. Studies retrieved from database searches were screened using our stringent inclusion and exclusion criteria, and Comprehensive Meta-Analysis Version 2.0 software was used for statistical analyses. In total, 115 studies were initially retrieved and after further selection, 11 were included in the meta-analysis. These 11 articles comprised 4840 patients with CHD in the case group and 4913 healthy participants in the control group. Meta-analysis revealed that APOA5 -1131T>C and APOC3 -455T>C polymorphisms increased CHD risk. In addition, subgroup analysis by ethnicity showed that while the -1131T>C polymorphism elevated the risk of CHD in the Caucasian population under both allelic and dominant models, this increased risk was observed only under a dominant model in the Asian population. The results of our meta-analysis point to a strong link between both APOA5 -1131T>C and APOC3 -455T>C polymorphisms and an increased risk of CHD. Thus, these polymorphisms constitute important predictive indicators of CHD susceptibility.

LysM receptor-like kinases to improve plant defense response against fungal pathogens

DOEpatents

Wan, Jinrong [Columbia, MO; Stacey, Gary [Columbia, MO; Stacey, Minviluz [Columbia, MO; Zhang, Xuecheng [Columbia, MO

2012-01-17

Perception of chitin fragments (chitooligosaccharides) is an important first step in plant defense response against fungal pathogen. LysM receptor-like kinases (LysM RLKs) are instrumental in this perception process. LysM RLKs also play a role in activating transcription of chitin-responsive genes (CRGs) in plants. Mutations in the LysM kinase receptor genes or the downstream CRGs may affect the fungal susceptibility of a plant. Mutations in LysM RLKs or transgenes carrying the same may be beneficial in imparting resistance against fungal pathogens.

LysM receptor-like kinases to improve plant defense response against fungal pathogens

DOEpatents

Wan, Jinrong; Stacey, Gary; Stacey, Minviluz; Zhang, Xuecheng

2013-10-15

Perception of chitin fragments (chitooligosaccharides) is an important first step in plant defense response against fungal pathogen. LysM receptor-like kinases (LysM RLKs) are instrumental in this perception process. LysM RLKs also play a role in activating transcription of chitin-responsive genes (CRGs) in plants. Mutations in the LysM kinase receptor genes or the downstream CRGs may affect the fungal susceptibility of a plant. Mutations in LysM RLKs or transgenes carrying the same may be beneficial in imparting resistance against fungal pathogens.

Stability, Elastic Properties, and Deformation of LiBN2: A Potential High-Energy Material.

PubMed

Zhu, Chunye; Zhu, Wenjun; Yang, Yanqiang

2018-05-15

Searching for high-energy-density materials is of great interest in scientific research and for industrial applications. Using an unbiased structure prediction method and first-principles calculations, we investigated the phase stability of LiBN 2 from 0 to100 GPa. Two new structures with space groups P4̅2 1 m and Pnma were discovered. The theoretical calculations revealed that Pnma LiBN 2 is stable with respect to a mixture of 1 / 3 Li 3 N, BN, and 1 / 3 N 2 above 22 GPa. The electronic band structure revealed that Pnma LiBN 2 has an indirect band gap of 2.3 eV, which shows a nonmetallic feature. The Pnma phase has a high calculated bulk modulus and shear modulus, indicating its incompressible nature. The microscopic mechanism of the structural deformation was demonstrated by ideal tensile shear strength calculations. It is worth mentioning that Pnma LiBN 2 is dynamically stable under ambient conditions. The decomposition of this phase is exothermic, releasing an energy of approximately 1.23 kJ/g at the PBE level. The results provide new thoughts for designing and synthesizing novel high-energy compounds in ternary systems.

Functional investigation of bone implant viability using radiotracers in a new model of osteonecrosis

PubMed Central

Schiper, Luis; Faintuch, Bluma Linkowski; da Silva Badaró, Roberto José; de Oliveira, Erica Aparecida; Chavez, Victor E. Arana; Chinen, Elisangela; Faintuch, Joel

2016-01-01

OBJECTIVES: Conventional imaging methods are excellent for the morphological characterization of the consequences of osteonecrosis; however, only specialized techniques have been considered useful for obtaining functional information. To explore the affinity of radiotracers for severely devascularized bone, a new mouse model of isolated femur implanted in a subcutaneous abdominal pocket was devised. To maintain animal mobility and longevity, the femur was harvested from syngeneic donors. Two technetium-99m-labeled tracers targeting angiogenesis and bone matrix were selected. METHODS: Medronic acid and a homodimer peptide conjugated with RGDfK were radiolabeled with technetium-99m, and biodistribution was evaluated in Swiss mice. The grafted and control femurs were evaluated after 15, 30 and 60 days, including computed tomography (CT) and histological analysis. RESULTS: Radiolabeling achieved high (>95%) radiochemical purity. The biodistribution confirmed good blood clearance 1 hour after administration. For 99mTc-hydrazinonicotinic acid (HYNIC)-E-[c(RGDfK)2, remarkable renal excretion was observed compared to 99mTc-methylene diphosphonate (MDP), but the latter, as expected, revealed higher bone uptake. The results obtained in the control femur were equal at all time points. In the implanted femur, 99mTc-HYNIC-E-[c(RGDfK)2 uptake was highest after 15 days, consistent with early angiogenesis. Regarding 99mTc-MDP in the implant, similar uptake was documented at all time points, consistent with sustained bone viability; however, the uptake was lower than that detected in the control femur, as confirmed by histology. CONCLUSIONS: 1) Graft viability was successfully diagnosed using radiotracers in severely ischemic bone at all time points. 2) Analogously, indirect information about angiogenesis could be gathered using 999mTc-HYNIC-E-[c(RGDfK)2. 3) These techniques appear promising and warrant further studies to determine their potential clinical applications. PMID

Spin filter effect of hBN/Co detector electrodes in a 3D topological insulator spin valve

NASA Astrophysics Data System (ADS)

Vaklinova, Kristina; Polyudov, Katharina; Burghard, Marko; Kern, Klaus

2018-03-01

Topological insulators emerge as promising components of spintronic devices, in particular for applications where all-electrical spin control is essential. While the capability of these materials to generate spin-polarized currents is well established, only very little is known about the spin injection/extraction into/out of them. Here, we explore the switching behavior of lateral spin valves comprising the 3D topological insulator Bi2Te2Se as channel, which is separated from ferromagnetic Cobalt detector contacts by an ultrathin hexagonal boron nitride (hBN) tunnel barrier. The corresponding contact resistance displays a notable variation, which is correlated with a change of the switching characteristics of the spin valve. For contact resistances below ~5 kΩ, the hysteresis in the switching curve reverses upon reversing the applied current, as expected for spin-polarized currents carried by the helical surface states. By contrast, for higher contact resistances an opposite polarity of the hysteresis loop is observed, which is independent of the current direction, a behavior signifying negative spin detection efficiency of the multilayer hBN/Co contacts combined with bias-induced spin signal inversion. Our findings suggest the possibility to tune the spin exchange across the interface between a ferromagnetic metal and a topological insulator through the number of intervening hBN layers.

Preclinical evaluation of a new, stabilized neurotensin(8--13) pseudopeptide radiolabeled with (99m)tc.

PubMed

García-Garayoa, Elisa; Bläuenstein, Peter; Bruehlmeier, Matthias; Blanc, Alain; Iterbeke, Koen; Conrath, Peter; Tourwé, Dirk; Schubiger, P August

2002-03-01

The rapid degradation of neurotensin (NT) limits its clinical use in cancer imaging and therapy. Thus, a new NT(8--13) pseudopeptide, NT-VIII, was synthesized. Some changes were introduced in the sequence of NT(8--13) to stabilize the molecule against enzymatic degradation: Arg(8) was N-methylated, and Lys and Tle replaced Arg(9) and Ile(12), respectively. Finally, (NalphaHis)Ac was coupled to the N-terminus for (99m)Tc(CO)(3) labeling. This peptide was characterized both in vitro and in vivo. The new analog was labeled with (99m)Tc(CO)(3). Its metabolic stability was analyzed both in human plasma and in HT-29 cells. Binding properties, receptor downregulation, and internalization were tested with HT-29 cells. Biodistribution was evaluated in nude mice with HT-29 xenografts. (99m)Tc(CO)(3)NT-VIII showed a high stability in plasma, where most of the peptide remained intact after 24 h of incubation at 37 degreesC. However, the degradation in HT-29 cells was more rapid (46% of intact (99m)Tc(CO)(3)NT-VIII after 24 h at 37 degreesC). Binding to NT1 receptors (NTR1) was saturable and specific. Scatchard analysis showed a high affinity for (99m)Tc(CO)(3)NT-VIII, with a dissociation constant similar to (125)I-NT (1.8 vs. 1.6 nmol/L). After interacting with NTR1, (99m)Tc(CO)(3)NT-VIII was rapidly internalized, with more than 90% internalized after 30 min. It also distributed and cleared rapidly in nude mice bearing HT-29 xenografts. The highest rates of accumulation were found in kidney and tumor at all time points tested. Tumor uptake was highly specific because it could be blocked by coinjection with a high dose of (NalphaHis)Ac-NT(8--13). Tumors were clearly visualized in scintigraphy images. The changes that were introduced stabilized the molecule against enzymatic degradation without affecting binding properties. Moreover, the increase in stability enhanced tumor uptake, making this derivative a promising candidate for clinical use.

Strain, stabilities and electronic properties of hexagonal BN bilayers

NASA Astrophysics Data System (ADS)

Fujimoto, Yoshitaka; Saito, Susumu

Hexagonal boron nitride (h-BN) atomic layers have been regarded as fascinating materials both scientifically and technologically due to the sizable band gap. This sizable band-gap nature of the h-BN atomic layers would provide not only new physical properties but also novel nano- and/or opto-electronics applications. Here, we study the first-principles density-functional study that clarifies the biaxial strain effects on the energetics and the electronic properties of h-BN bilayers. We show that the band gaps of the h-BN bilayers are tunable by applying strains. Furthermore, we show that the biaxial strains can produce a transition from indirect to direct band gaps of the h-BN bilayer. We also discuss that both AA and AB stacking patterns of h-BN bilayer become feasible structures because h-BN bilayers possess two different directions in the stacking patterns. Supported by MEXT Elements Strategy Initiative to Form Core Research Center through Tokodai Institute for Element Strategy, JSPS KAKENHI Grant Numbers JP26390062 and JP25107005.

Fabrication of AlN/BN bishell hollow nanofibers by electrospinning and atomic layer deposition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haider, Ali; Kayaci, Fatma; Uyar, Tamer

2014-09-01

Aluminum nitride (AlN)/boron nitride (BN) bishell hollow nanofibers (HNFs) have been fabricated by successive atomic layer deposition (ALD) of AlN and sequential chemical vapor deposition (CVD) of BN on electrospun polymeric nanofibrous template. A four-step fabrication process was utilized: (i) fabrication of polymeric (nylon 6,6) nanofibers via electrospinning, (ii) hollow cathode plasma-assisted ALD of AlN at 100 °C onto electrospun polymeric nanofibers, (iii) calcination at 500 °C for 2 h in order to remove the polymeric template, and (iv) sequential CVD growth of BN at 450 °C. AlN/BN HNFs have been characterized for their chemical composition, surface morphology, crystal structure, and internal nanostructuremore » using X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray spectroscopy, and selected area electron diffraction. Measurements confirmed the presence of crystalline hexagonal BN and AlN within the three dimensional (3D) network of bishell HNFs with relatively low impurity content. In contrast to the smooth surface of the inner AlN layer, outer BN coating showed a highly rough 3D morphology in the form of BN nano-needle crystallites. It is shown that the combination of electrospinning and plasma-assisted low-temperature ALD/CVD can produce highly controlled multi-layered bishell nitride ceramic hollow nanostructures. While electrospinning enables easy fabrication of nanofibrous template, self-limiting reactions of plasma-assisted ALD and sequential CVD provide control over the wall thicknesses of AlN and BN layers with sub-nanometer accuracy.« less

Thermal Conductivity Enhancement by Optical Phonon Sub-Band Engineering of Nanostructures Based on C and BN

DTIC Science & Technology

2002-01-01

Thermal Conductivity Enhancement by Optical Phono n Sub-Band Engineering of Nanostructures Based on C and BN DARPA CONTRACT MDA972-02-C-0044... Engineering in 3-D Nanostructures Based on C an d BN Nanotubes " 1.3.1a. Phonon dynamics and thermal properties of zigzag carbon nanotubes Content I...Conductivity. Enhancement by Optical Phonon Sub-Bands Engineering in 3-D Nanostructure s Based on C and BN Nanotubes " . Here, the dynamics of the heat

Ab initio multireference study of the BN molecule

NASA Technical Reports Server (NTRS)

Martin, J. M. L.; Lee, Timothy J.; Scuseria, Gustavo E.; Taylor, Peter R.

1992-01-01

The lowest 1Sigma(+) and 3Pi states of the BN molecule are studied using multireference configuration interaction (MRCI) and averaged coupled-pair functional (ACPF) methods and large atomic natural orbital (ANO) basis sets, as well as several coupled cluster methods. Our calculations strongly support a 3Pi ground state, but the a1Sigma(+) state lies only 381 +/- 100/cm higher. The a1Sigma(+) state wave function exhibits strong multireference character and, consequently, the predictions of the perturbationally-based single-reference CCSD(T) coupled cluster method are not as reliable in this case as the multireference results. The theoretical predictions for the spectroscopic constants of BN are in good agreement with experiment for the Chi3Pi state, but strongly suggest a misassignment of the fundamental vibrational frequency for the a1Sigma(+) state.

Synthesis and Comparison of Two cBN Composites with Starting Ternary Carbide Binders

NASA Astrophysics Data System (ADS)

Yue, Zhenming; Yang, Limin; Gong, Jianhong; Gao, Jun

2018-04-01

Ti3SiC2 and Ti3AlC2 are two promising binders for the ultrahard composite polycrystalline cubic boron nitride (PcBN). In this study, the cBN composites with Ti3SiC2 and Ti3AlC2 binders with different binder contents were synthesized under the same high pressure ( 5.5 GPa) and high temperature (1350 °C) conditions. Their mechanical properties were measured separately, including Vickers hardness, bending hardening, and compression hardening. Together with XRD results, the phase compounds were also investigated. The decomposition and reaction processes were affected by binder content. Some new compounds formed during sintering, these compounds were TiC, TiSi2, SiC, TiB2, SiB4, TiB2, and TiC0.7N0.3 in Ti3SiC2-cBN composites, as well as TiC0.7N0.3, TiB2, and AlN in Ti3AlC2-cBN composites. The microstructure of the cracks surface was obtained after the bending tests, and was used to further investigate and compare their crack mode by SEM. The crack surface profile and elementary analysis on the oxidative surface were also discussed.

Synthesis and Comparison of Two cBN Composites with Starting Ternary Carbide Binders

NASA Astrophysics Data System (ADS)

Yue, Zhenming; Yang, Limin; Gong, Jianhong; Gao, Jun

2018-05-01

Ti3SiC2 and Ti3AlC2 are two promising binders for the ultrahard composite polycrystalline cubic boron nitride (PcBN). In this study, the cBN composites with Ti3SiC2 and Ti3AlC2 binders with different binder contents were synthesized under the same high pressure ( 5.5 GPa) and high temperature (1350 °C) conditions. Their mechanical properties were measured separately, including Vickers hardness, bending hardening, and compression hardening. Together with XRD results, the phase compounds were also investigated. The decomposition and reaction processes were affected by binder content. Some new compounds formed during sintering, these compounds were TiC, TiSi2, SiC, TiB2, SiB4, TiB2, and TiC0.7N0.3 in Ti3SiC2-cBN composites, as well as TiC0.7N0.3, TiB2, and AlN in Ti3AlC2-cBN composites. The microstructure of the cracks surface was obtained after the bending tests, and was used to further investigate and compare their crack mode by SEM. The crack surface profile and elementary analysis on the oxidative surface were also discussed.

Cloning and characterization of newly isolated lipase from Enterobacter sp. Bn12.

PubMed

Farrokh, Parisa; Yakhchali, Bagher; Karkhane, Ali Asghar

2014-01-01

A mesophilic Enterobacter sp. Bn12 producing an alkaline thermostable lipase was isolated from soil in Tehran, Iran. The lipase gene (ELBn12) was identified from a genomic library. Sequence analysis of the DNA fragment revealed an open reading frame of 879 bp encoding a lipase with a molecular mass of 31.3 kDa. The deduced amino acid sequence showed 96% identity with a lipase of Enterobacter sp. Ag1 and the identity of their DNA sequences was 88.9%. ELBn12 belongs to the lipase subfamily I.1 and its catalytic triad consists of Ser82, Asp237 and His259. The lipase was expressed in Escherichia coli (BL21) pLysS and partially purified by anion exchange chromatography. The maximum activity of ELBn12 was obtained at temperature of 60 °C and pH 8.0 towards tricaprylin (C8) and its specific activity was around 2900 U/mg. ELBn12 was stable within a broad pH range from 6.0 to 11.0. The enzyme showed high stability in both polar and nonpolar organic solvents at 50% (v/v). The lipase activity was enhanced in the presence of 10 mM of Ca(2+), Mg(2+) and K(+), while heavy metals (Fe(3+) and Zn(2+)) had strong inhibitory effect. ELBn12 showed high activity in the presence of 1% (w/v) nonionic surfactants, however ionic surfactants inhibited the lipolytic activity. ELBn12 characteristics show that it has a potential to be used in various industrial processes.

Cloning and characterization of newly isolated lipase from Enterobacter sp. Bn12

PubMed Central

Farrokh, Parisa; Yakhchali, Bagher; Karkhane, Ali Asghar

2014-01-01

A mesophilic Enterobacter sp. Bn12 producing an alkaline thermostable lipase was isolated from soil in Tehran, Iran. The lipase gene (ELBn12) was identified from a genomic library. Sequence analysis of the DNA fragment revealed an open reading frame of 879 bp encoding a lipase with a molecular mass of 31.3 kDa. The deduced amino acid sequence showed 96% identity with a lipase of Enterobacter sp. Ag1 and the identity of their DNA sequences was 88.9%. ELBn12 belongs to the lipase subfamily I.1 and its catalytic triad consists of Ser82, Asp237 and His259. The lipase was expressed in Escherichia coli (BL21) pLysS and partially purified by anion exchange chromatography. The maximum activity of ELBn12 was obtained at temperature of 60 °C and pH 8.0 towards tricaprylin (C8) and its specific activity was around 2900 U/mg. ELBn12 was stable within a broad pH range from 6.0 to 11.0. The enzyme showed high stability in both polar and nonpolar organic solvents at 50% (v/v). The lipase activity was enhanced in the presence of 10 mM of Ca2+, Mg2+ and K+, while heavy metals (Fe3+ and Zn2+) had strong inhibitory effect. ELBn12 showed high activity in the presence of 1% (w/v) nonionic surfactants, however ionic surfactants inhibited the lipolytic activity. ELBn12 characteristics show that it has a potential to be used in various industrial processes. PMID:25242958

Effect of BN coating on the strength of a mullite type fiber

NASA Astrophysics Data System (ADS)

Chawla, K. K.; Xu, Z. R.; Ha, J.-S.; Schmücker, M.; Schneider, H.

1997-09-01

Nextel 480 is a polycrystalline essentially mullite fiber (70 wt.-% Al2O3+28 wt.-% SiO2+2 wt.-% B2O3). Different thicknesses of BN were applied as coatings on this fiber. Optical, scanning electron, and transmission electron microscopy were used to characterize the microstructure of the coatings and fibers. The effects of coating and high temperature exposure on the fiber strength were investigated using two-parameter Weibull distribution. TEM examination showed that the BN coating has a turbostratic structure, with the basal planes lying predominantly parallel to the fiber surface. Such an orientation of coating is desirable for easy crack deflection and subsequent fiber pullout in a composite. The BN coated Nextel 480 fiber showed that Weibull mean strength increased first and then decreased with increasing coating thickness. This was due to the surface flaw healing effect of the coating (up to 0.3 μm) while in the case of thick BN coating (1 μm), the soft nature of the coating material had a more dominant effect and resulted in a decrease of the fiber strength. High temperature exposure of Nextel 480 resulted in grain growth, which led to a strength loss.

(99m)Tc(CO)3(NTA): a (99m)Tc renal tracer with pharmacokinetic properties comparable to those of (131)I-OIH in healthy volunteers.

PubMed

Taylor, Andrew T; Lipowska, Malgorzata; Marzilli, Luigi G

2010-03-01

Studies in rats showed that the pharmacokinetics of the tricarbonyl core radiopharmaceutical (99m)Tc(CO)(3)-nitrilotriacetic acid, (99m)Tc(CO)(3)(NTA), were essentially identical to those of (131)I ortho-iodohippuran ((131)I-OIH), the clinical gold standard for the measurement of effective renal plasma flow. Our objective was to compare the pharmacokinetics of these 2 tracers in healthy volunteers. (99m)Tc(CO)(3)(NTA) was prepared with commercially available NTA and a commercially available kit and isolated by reversed-phase high-performance liquid chromatography. Approximately 74 MBq (2 mCi) of (99m)Tc(CO)(3)(NTA) were coinjected with 9.25 MBq (250 microCi) of (131)I-OIH in 9 volunteers, and simultaneous imaging of each tracer was performed for 24 min. Plasma clearances were determined from 8 blood samples obtained 3-90 min after injection using the single-injection, 2-compartment model. Plasma protein binding, red cell uptake, and percentage injected dose in the urine at 30 and 180 min were determined. There was no difference in the plasma clearances of (99m)Tc(CO)(3)(NTA) and (131)I-OIH, 475 +/- 105 mL/min versus 472 +/- 108 mL/min, respectively. The plasma protein binding and red cell uptake of (99m)Tc(CO)(3)(NTA) were 43% +/- 5% and 9% +/- 6%, respectively; both values were significantly lower (P < 0.001) than the plasma protein binding (75% +/- 3%) and red cell uptake (17% +/- 5%) of (131)I-OIH. There was no significant difference in the percentage injected dose recovered in the urine at 30 min and at 3 h; for comparison, the percentage dose in the urine at 3 h was 91% +/- 4% for (99m)Tc(CO)(3)(NTA) and 91% +/- 6% for (131)I-OIH (P = 0.96). Image quality with (99m)Tc(CO)(3)(NTA) was excellent, and the renogram parameters were similar to those of (131)I-OIH. Preliminary results in healthy volunteers suggest that the pharmacokinetic behavior of (99m)Tc(CO)(3)(NTA) is comparable to that of (131)I-OIH.

Spin-polarized electron transport in hybrid graphene-BN nanoribbons

NASA Astrophysics Data System (ADS)

Gao, Song; Lu, Wei; Zheng, Guo-Hui; Jia, Yalei; Ke, San-Huang

2017-05-01

The experimental realization of hybrid graphene and h-BN provides a new way to modify the electronic and transport properties of graphene-based materials. In this work, we investigate the spin-polarized electron transport in hybrid graphene-BN zigzag nanoribbons by performing first-principles nonequilibrium Green’s function method calculations. A 100% spin-polarized electron transport in a large energy window around the Fermi level is found and this behavior is independent of the ribbon width as long as there contain 3 zigzag carbon chains. This behavior may be useful in making perfect spin filters.

Anticancer activity of an imageable curcuminoid 1-[2-aminoethyl-(6-hydrazinopyridine-3-carbamidyl)-3,5-bis-(2-fluorobenzylidene)-4-piperidone (EFAH).

PubMed

Lagisetty, Pallavi; Subramaniam, Dharmalingam; Sahoo, Kaustuv; Anant, Shrikant; Awasthi, Vibhudutta

2012-02-01

3,5-Bis(2-fluorobenzylidine)-4-piperidone or EF24 is a potent anticancer derivative of curcumin. Using an amine derivative of EF24, we synthesized a hydrazinonicotinic acid conjugate, EFAH, for Tc-99m radiolabelling and single photon emission tomography imaging. The aqueous solubility of EFAH (3.5 mg/mL) was significantly more than that of EF24 (1.2 mg/mL); the octanol/water partition coefficient of EFAH was estimated at log P = 0.33. As an antiproliferative agent, EFAH was as effective as EF24 in suppressing the proliferation of H441, MiaPaCa-2 and Panc-1 cells. Daily intraperitoneal injection of EFAH (5 μg) for 3 weeks in mice carrying xenografts of Panc-1 pancreatic cancer showed a mean tumour volume reduction of 79%; the tumour weight decreased by 82% in the treated group. For imaging and biodistribution, EFAH was labelled with Tc-99m (98% RCY) and intravenously administered in rats. Approximately 23.7% and 14.3% of injected dose accumulated in liver and intestine, respectively, suggesting that EFAH is mostly eliminated by hepatobiliary route. The results indicate that HYNIC modification of EF24 for Tc-99m radiolabelling does not affect its antiproliferative efficacy. For the first time, a visual biodisposition of EF24 in a live animal model has been demonstrated. Such knowledge could be of benefit in developing therapeutic curcuminoids, such as EF24. © 2011 John Wiley & Sons A/S.

How lithium atoms affect the first hyperpolarizability of BN edge-doped graphene.

PubMed

Song, Yao-Dong; Wu, Li-Ming; Chen, Qiao-Ling; Liu, Fa-Kun; Tang, Xiao-Wen

2016-01-01

How do lithium atoms affect the first hyperpolarizability (β0) of boron-nitrogen (BN) edge-doped graphene. In this work, using pentacene as graphene model, Lin@BN-1 edge-doped pentacene and Lin@BN-2 edge-doped pentacene (n = 1, 5) were designed to study this problem. First, two models (BN-1 edge-doped pentacene, and BN-2 edge-doped pentacene ) were formed by doping the BN into the pentacene with different order, and then Li@BN-1 edge-doped pentacene and Li@ BN-2 edge-doped pentacene were obtained by substituting the H atom in BN edge-doped pentacene with a Li atom. The results show that the first hyperpolarizabilities of BN-1 edge-doped pentacene and Li@BN-1 edge-doped pentacene were 4059 a.u. and 6249 a.u., respectively; the first hyperpolarizabilities of BN-2 edge-doped pentacene and Li@BN-2 edge-doped pentacene were 2491 a.u. and 4265 a.u., respectively. The results indicate that the effect of Li substitution is to greatly increase the β0 value. To further enhance the first hyperpolarizability, Li5@ BN-1 edge-doped pentacene and Li5@BN-2 edge-doped pentacene were designed, and were found to exhibit considerably larger first hyperpolarizabilities (β0) (12,112 a.u. and 7921a.u., respectively). This work may inspire further study of the nonlinear properties of BN edge-doped graphene.

Initial stages of growth and the influence of temperature during chemical vapor deposition of sp{sup 2}-BN films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chubarov, Mikhail; Pedersen, Henrik; Högberg, Hans

2015-11-15

Knowledge of the structural evolution of thin films, starting by the initial stages of growth, is important to control the quality and properties of the film. The authors present a study on the initial stages of growth and the temperature influence on the structural evolution of sp{sup 2} hybridized boron nitride (BN) thin films during chemical vapor deposition (CVD) with triethyl boron and ammonia as precursors. Nucleation of hexagonal BN (h-BN) occurs at 1200 °C on α-Al{sub 2}O{sub 3} with an AlN buffer layer (AlN/α-Al{sub 2}O{sub 3}). At 1500 °C, h-BN grows with a layer-by-layer growth mode on AlN/α-Al{sub 2}O{sub 3} upmore » to ∼4 nm after which the film structure changes to rhombohedral BN (r-BN). Then, r-BN growth proceeds with a mixed layer-by-layer and island growth mode. h-BN does not grow on 6H-SiC substrates; instead, r-BN nucleates and grows directly with a mixed layer-by-layer and island growth mode. These differences may be caused by differences in substrate surface temperature due to different thermal conductivities of the substrate materials. These results add to the understanding of the growth process of sp{sup 2}-BN employing CVD.« less

Thermal Conductivity Enhancement by Optical Phonon Sub-Band Engineering of Nanostructures Based on C and BN

DTIC Science & Technology

2005-09-01

Thermal Conductivity Enhancement by Optical Phonon Sub-Band Engineering of Nanostructures Based on C and BN DARPA CONTRACT MDA972-02-C-0044...AND SUBTITLE Thermal Conductivity Enhancement by Optical Phonon Sub-Band Engineering of Nanostructures Based on C and BN 5a. CONTRACT NUMBER 5b...Conductivity. Enhancement by Optical Phonon Sub-Bands Engineering in 3-D Nanostructures Based on C and BN Nanotubes" 1.3.1a. Phonon dynamics

Influence of BN fiber coatings on the interfacial structure of sapphire fiber reinforced NiAl composites

NASA Astrophysics Data System (ADS)

Reichert, K.; Wen, K.; Cremer, R.; Hu, W.; Neuschütz, D.; Gottstein, G.

2001-07-01

A new concept for a tailored fiber-matrix interface for sapphire fiber reinforced NiAl matrix composites is proposed, consisting of an initial hexagonal boron nitride (hBN) fiber coating. For this, single crystal Al 2O 3 fibers were coated with hBN by chemical vapor deposition (CVD). Following a comprehensive characterization of the CVD coating as to composition and structure by means of X-ray photoelectron spectroscopy (XPS) and grazing incidence X-ray diffraction (GIXRD), the fiber reinforced NiAl matrix composites were fabricated by diffusion bonding at 1400°C. The interfaces NiAl/BN and BN/Al 2O 3 were analyzed by scanning electron microscopy (SEM), analytical transmission electron microscopy (TEM), and selected area diffraction (SAD). An interfacial reaction between NiAl and hBN to form AlN was revealed using these analytical techniques.

Transcriptional Activation of Pyoluteorin Operon Mediated by the LysR-Type Regulator PltR Bound at a 22 bp lys Box in Pseudomonas aeruginosa M18

PubMed Central

Wang, Guohao; Xu, Yuquan

2012-01-01

Pseudomonas aeruginosa M18, a rhizosphere-isolated bacterial strain showing strong antifungal activity, can produce secondary metabolites such as phenazine-1-carboxylic acid and pyoluteorin (Plt). The LysR-type transcriptional regulator PltR activates the Plt biosynthesis operon pltLABCDEFG, the expression of which is induced by Plt. Here, we identified and characterized the non-conserved pltL promoter (pltLp) specifically activated by PltR and its upstream neighboring lys box from the complicated pltR–pltL intergenic sequence. The 22 bp palindromic lys box, which consists of two 9 bp complementary inverted repeats interrupted by 4 bp, was found to contain the conserved, GC-rich LysR-binding motif (T-N11-A). Evidence obtained in vivo from mutational and lacZ report analyses and in vitro from electrophoretic mobility shift assays reveals that the PltR protein directly bound to the pltLp region as the indispensable binding motif “lys box”, thereby transcriptionally activating the pltLp-driven plt operon expression. Plt, as a potential non-essential coinducer of PltR, specifically induced the pltLp expression and thus strengthened its biosynthetic plt operon expression. PMID:22761817

Radiofrequency ablation, an effective modality of treatment in tumor-induced osteomalacia: a case series of three patients.

PubMed

Jadhav, Swati; Kasaliwal, Rajeev; Shetty, Nitin S; Kulkarni, Suyash; Rathod, Krantikumar; Popat, Bhavesh; Kakade, Harshal; Bukan, Amol; Khare, Shruti; Budyal, Sweta; Jagtap, Varsha S; Lila, Anurag R; Bandgar, Tushar; Shah, Nalini S

2014-09-01

Tumor-induced osteomalacia is curable if the tumors can be totally excised. However, when the tumors are present in locations that make surgery disproportionately risky, the need for less invasive strategies like radiofrequency ablation (RFA) is realized. We describe three patients with suspected tumor-induced osteomalacia who were treated in our department between 2006 and 2013 with tumors in surgically difficult locations and were subjected to single or multiple sessions of RFA. The response was documented in terms of symptomatic improvement, phosphorus normalization, and follow-up (99m)Technitium-labelled hydrazinonicotinyl-Tyr3-octreotide ((99m)Tc HYNIC TOC) scan. Two of the three individuals, patient A (with a 1.5 × 1.2-cm lesion in the head of the right femur) and patient B (with a 1.3 × 1.2-cm lesion on the endosteal surface of the shaft of the left femur), achieved complete remission with single sessions of RFA. Three months after the procedure, (99m)Tc HYNIC TOC scans revealed the absence of uptake at the previous sites, corroborating with the clinical improvement and phosphorus normalization. Patient C had a large 5.6 × 6.5-cm complex lesion in the lower end of the left femur with irregular margins, loculations, and bone grafts placed in previous surgery. He failed to achieve remission after multiple sessions of RFA due to the complex nature of the lesion, although the tumor burden was reduced significantly as documented on serial (99m)Tc HYNIC TOC scans. Although surgery remains the treatment of choice, RFA could be an effective, less invasive, and safe modality of treatment in judiciously selected patients.

Thermodynamic description of Tc(iv) solubility and carbonate complexation in alkaline NaHCO3-Na2CO3-NaCl systems.

PubMed

Baumann, A; Yalçıntaş, E; Gaona, X; Polly, R; Dardenne, K; Prüßmann, T; Rothe, J; Altmaier, M; Geckeis, H

2018-03-28

The solubility of 99 Tc(iv) was investigated in dilute to concentrated carbonate solutions (0.01 M ≤ C tot ≤ 1.0 M, with C tot = [HCO 3 - ] + [CO 3 2- ]) under systematic variation of ionic strength (I = 0.3-5.0 M NaHCO 3 -Na 2 CO 3 -NaCl-NaOH) and pH m (-log[H + ] = 8.5-14.5). Strongly reducing conditions (pe + pH m ≈ 2) were set with Sn(ii). Carbonate enhances the solubility of Tc(iv) in alkaline conditions by up to 3.5 log 10 -units compared to carbonate-free systems. Solvent extraction and XANES confirmed that Tc was kept as +IV during the timeframe of the experiments (≤ 650 days). Solid phase characterization performed by XAFS, XRD, SEM-EDS, chemical analysis and TG-DTA confirmed that TcO 2 ·0.6H 2 O(am) controls the solubility of Tc(iv) under the conditions investigated. Slope analysis of the solubility data in combination with solid/aqueous phase characterization and DFT calculations indicate the predominance of the species Tc(OH) 3 CO 3 - at pH m ≤ 11 and C tot ≥ 0.01 M, for which thermodynamic and activity models are derived. Solubility data obtained above pH m ≈ 11 indicates the formation of previously unreported Tc(iv)-carbonate species, possibly Tc(OH) 4 CO 3 2- , although the likely formation of additional complexes prevents deriving a thermodynamic model valid for this pH m -region. This work provides the most comprehensive thermodynamic dataset available for the system Tc 4+ -Na + -Cl - -OH - -HCO 3 - -CO 3 2- -H 2 O(l) valid under a range of conditions relevant for nuclear waste disposal.

Origin and dispersal of atypical aldehyde dehydrogenase ALDH2487Lys.

PubMed

Luo, Huai-Rong; Wu, Gui-Sheng; Pakstis, Andrew J; Tong, Li; Oota, Hiroki; Kidd, Kenneth K; Zhang, Ya-Ping

2009-04-15

The East Asian respond with a marked facial flushing and mild to moderate symptoms of intoxication after drinking the amounts of alcohol that has no detectable effect on European. The alcohol sensitivity in Orientals is due to a delayed oxidation of acetaldehyde by an atypical aldehyde dehydrogenase ALDH2487Lys, which is resulted from a structural mutation in gene ALDH2. The atypical ALDH2487Lys allele has been associated with various phenotypic statuses, such as protective against alcohol dependence and the risk of alcohol-related digestive tract cancers. Here, we have examined this SNP, adjacent four non-coding SNPs, and one downstream STRP on ALDH2 gene, in total of 1072 unrelated healthy individuals from 14 Chinese populations and 130 Indian individuals. Five major haplotypes based on five SNPs across the ALDH2 gene 40 kb were found in all East Asian populations. The frequencies of the ancestral haplotype GCCTG and the East Asian special haplotype GCCTA containing the atypical ALDH2487Lys allele were 44.8% and 14.9%, respectively. The frequency of the atypical ALDH2487Lys allele or the East Asian specific haplotype GCCTA is high in Yunnan, South coastal, east coastal of China, and decreased gradually toward inland China, West, Northwest and North China. Combined with demographic history in East Asian, our results showed that the presence of ALDH2487Lys allele in peripheral regions of China might be the results of historical migration events from China to these regions. The origin of ALDH2487Lys could be possibly traced back to ancient Pai-Yuei tribe in South China.

Papain cleavage of the 38,000-dalton fragment inhibits the binding of 4, 4'-diisothiocyanostilbene-2, 2'-disulfonate to lys-539 on the 60,000-dalton fragment in human band 3.

PubMed

Yamaguchi, Takeo; Kojima, Hideaki; Kawaguchi, Shiori; Shimada, Maiko; Aso, Haruka

2017-08-01

Human band 3 is a 98-kDa transmembrane (TM) protein comprising 14 TM segments. Papain cleavages band 3 into 38- and 60-kDa fragments. Under vigorous conditions, the cleavage of the loop region between the TM 7 of gate domain and the TM 8 of core domain in the 38-kDa fragment produces 7- and 31-kDa fragments. Conformational changes of the TM 5 segment containing Lys-539 by cleavage of the 38-kDa fragment remain unclear. Pressure-induced haemolysis of erythrocytes was suppressed by binding of 4, 4'-diisothiocyanostilbene-2, 2'-disulfonate (DIDS) to Lys-539. Such effect of DIDS was not observed upon cleavage of the 38-kDa fragment, because of inhibition of DIDS binding to Lys-539. Using fluorescence of DIDS labelled to Lys-539, conformational changes of band 3 were examined. Fluorescence spectra demonstrated that the molecular motion of DIDS is more restricted upon digestion of the 38-kDa fragment. Interestingly, the quenching of DIDS fluorescence showed that Hg2+ is less accessible to DIDS upon digestion of the 38-kDa fragment. Taken together, we propose that the conformational changes of the TM 5 segment characterized by the sequestration and restricted motion of Lys-539 are induced by the cleavage of the loop region between the TM 7 and the TM 8. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Nanostructured BN-Mg composites: features of interface bonding and mechanical properties.

PubMed

Kvashnin, Dmitry G; Krasheninnikov, Arkady V; Shtansky, Dmitry; Sorokin, Pavel B; Golberg, Dmitri

2016-01-14

Magnesium (Mg) is one of the lightest industrially used metals. However, wide applications of Mg-based components require a substantial enhancement of their mechanical characteristics. This can be achieved by introducing small particles or fibers into the metal matrix. Using first-principles calculations, we investigate the stability and mechanical properties of a nanocomposite made of magnesium reinforced with boron nitride (BN) nanostructures (BN nanotubes and BN monolayers). We show that boron vacancies at the BN/Mg interface lead to a substantial increase in BN/Mg bonding establishing an efficient route towards the development of BN/Mg composite materials with enhanced mechanical properties.

Electronic structure of graphene- and BN-supported phosphorene

NASA Astrophysics Data System (ADS)

Davletshin, Artur R.; Ustiuzhanina, Svetlana V.; Kistanov, Andrey A.; Saadatmand, Danial; Dmitriev, Sergey V.; Zhou, Kun; Korznikova, Elena A.

2018-04-01

By using first-principles calculations, the effects of graphene and boron nitride (BN) substrates on the electronic properties of phosphorene are studied. Graphene-supported phosphorene is found to be metallic, while the BN-supported phosphorene is a semiconductor with a moderate band gap of 1.02 eV. Furthermore, the effects of the van der Waals interactions between the phosphorene and graphene or BN layers by means of the interlayer distance change are investigated. It is shown that the interlayer distance change leads to significant band gap size modulations and direct-indirect band gap transitions in the phosphorene-BN heterostructure. The presented band gap engineering of phosphorene may be a powerful technique for the fabrication of high-performance phosphorene-based nanodevices.

AmeriFlux US-Bn3 Bonanza Creek, 1999 Burn site near Delta Junction

DOE Data Explorer

Randerson, James [University of California, Irvine

2016-01-01

This is the AmeriFlux version of the carbon flux data for the site US-Bn3 Bonanza Creek, 1999 Burn site near Delta Junction. Site Description - The Delta Junction 1999 Burn site is located near Delta Junction, just to the north of the Alaska Range in interior Alaska. All three Delta Junction sites are within a 15-km radius of one another. Composed of a combination of alluvial outwashes, floodplains, and low terraces dissected by glacial streams originating in the nearby Alaska Range. The Donnelly Flats fire burned ~7,600 ha of black spruce (Picea mariana) during June 1999. The boles of the black spruce remained standing 3 years after the fire. 70% of the surface was not covered by vascular plants.

Tunable magnetotransport in Fe/hBN/graphene/hBN/Pt(Fe) epitaxial multilayers

NASA Astrophysics Data System (ADS)

Magnus Ukpong, Aniekan

2018-03-01

Theoretical and computational analysis of the magnetotransport properties and spin-transfer torque field-induced switching of magnetization density in vertically-stacked multilayers is presented. Using epitaxially-capped free layers of Pt and Fe, atom-resolved magnetic moments and spin-transfer torques are computed at finite bias. The calculations are performed within linear response approximation to the spin-density reformulation of the van der Waals density functional theory. Dynamical spin excitations are computed as a function of a spin-transfer torque induced magnetic field along the magnetic easy axis, and the corresponding spin polarization perpendicular to the easy axis is obtained. Bias-dependent giant anisotropic magnetoresistance of up to 3200% is obtained in the nonmagnetic-metal-capped Fe/hBN/graphene/hBN/Pt multilayer architecture. Since this specific heterostructure is not yet fabricated and characterized, the predicted high performance has not been demonstrated experimentally. Nevertheless, similar calculations performed on the Fe/hBN/Co stack show that the tunneling magnetoresistance obtained at the Fermi-level is in excellent agreement with results of recent magnetotransport measurements on magnetic tunnel junctions that contain the monolayer hBN tunnel region. The magnitude of the spin-transfer torque is found to increase as the tunneling spin current increases, and this activates the magnetization switching process due to increased charge accumulation. This mechanism causes substantial spin backflow, which manifests as rapid undulations in the bias-dependent tunneling spin currents. The implication of these findings on the design of nanoscale spintronic devices with spin-transfer torque tunable magnetization density is discussed. Insights derived from this study are expected to enhance the prospects for developing and integrating artificially assembled van der Waals multilayer heterostructures as the preferred material platform for efficient

EDN1 Lys198Asn is associated with diabetic retinopathy in type 2 diabetes

PubMed Central

Li, Haitao; Louey, Janice W.C.; Choy, Kwong Wai; Liu, David T.L.; Chan, Wai Man; Chan, Yiu Man; Fung, Nicholas S.K.; Fan, Bao Jian; Baum, Larry; Chan, Juliana C.N.; Lam, Dennis S.C.

2008-01-01

Purpose We tested the hypothesis that genetic variants in vasoactive and angiogenic factors regulating the retina vasculature contribute to the development of diabetic retinopathy (DR). Methods A case-control study was performed to study the genetic association between DR and polymorphic variants of EDN1 (Lys198Asn), LTA (IVS1–80C>A, IVS1–206G>C, IVS1–252A>G), eNOS (Glu298Asp), and ITGA2 (BgI II) in a Chinese population with type 2 diabetes mellitus. A well defined population with type 2 diabetes, consisting of 127 controls and 216 DR patients, was recruited. Results A higher frequency of the Asn/Asn genotype of EDN1 was found in individuals with at least 10 years of diabetes and no retinopathy (controls) compared with DR patients with any duration of diabetes (DR: 2.3%; control: 11.0%; p=0.0002). The Asn allele was also more frequent in controls than DR patients (DR: 16.4%; control: 29.5%; p=0.007). Multiple logistic regression analysis showed that the Asn/Asn genotype was the factor most significantly associated with reduced risk of DR (odds ratio=0.19; 95% CI: 0.07-0.53; p=0.002) and with late onset of diabetes (Asn/Asn: 59 years; Lys/Lys + Lys/Asn: 53 years; p=0.02). Moreover, the Lys/Lys genotype was more common among patients with nonproliferative (75.7%) than proliferative DR (56.9%; p=0.008). The distributions of Lys198Asn alleles in hypertension did not differ from normotensive subjects. No associations between DR and polymorphisms of LTA, eNOS, or ITGA2 were detected, and there were no detectable gene-gene or gene-environmental interactions among the polymorphisms. Conclusions The Asn/Asn genotype of EDN1 was associated with a reduced risk of DR and with delayed onset of type 2 diabetes. PMID:18806884

Fabrication and properties of SiNO continuous fiber reinforced BN wave-transparent composites

NASA Astrophysics Data System (ADS)

Cao, F.; Fang, Z.; Chen, F.; Shen, Q.; Zhang, C.

2012-06-01

SiNO continuous fiber reinforced boron nitride (BN) wave-transparent composites (SiNO f /BN) have been fabricated by a precursor infiltration pyrolysis (PIP) method using borazine as the precursor. The densification behavior, microstructures, mechanical properties, and dielectric properties of the composites have been investigated. After four PIP cycles, the density of the composites had increased from 1.1 g·cm-3 to 1.81 g·cm-3. A flexural strength of 128.9 MPa and an elastic modulus of 23.5 GPa were achieved. The obtained composites have relatively high density and the fracture faces show distinct fiber pull-out and interface de-bonding features. The dielectric properties of the SiNO f /BN composites, including the dielectric constant of 3.61 and the dielectric loss angle tangent of 5.7×10-3, are excellent for application as wave-transparent materials.

The Structure and Stability of Bn(+) Clusters

NASA Technical Reports Server (NTRS)

Ricca, Alessandra; Bauschlicher, Charles W., Jr.; Langhoff, Stephen R. (Technical Monitor)

1995-01-01

The geometries of B+n clusters for n less than 14 have been optimized using density functional theory with the B3LYP functional. The most stable structure for each cluster is planar or quasi-planar. The B3LYP fragmentation energies are calibrated using coupled cluster theory. Overall, our corrected fragmentation energies are in reasonable agreement with experiment. Our results are compared with previous theoretical results.

Specialization of the paralogue LYS21 determines lysine biosynthesis under respiratory metabolism in Saccharomyces cerevisiae.

PubMed

Quezada, Héctor; Aranda, Cristina; DeLuna, Alexander; Hernández, Hugo; Calcagno, Mario L; Marín-Hernández, Alvaro; González, Alicia

2008-06-01

In the yeast Saccharomyces cerevisiae, the first committed step of the lysine biosynthetic pathway is catalysed by two homocitrate synthases encoded by LYS20 and LYS21. We undertook a study of the duplicate homocitrate synthases to analyse whether their retention and presumable specialization have affected the efficiency of lysine biosynthesis in yeast. Our results show that during growth on ethanol, homocitrate is mainly synthesized through Lys21p, while under fermentative metabolism, Lys20p and Lys21p play redundant roles. Furthermore, results presented in this paper indicate that, in contrast to that which had been found for Lys20p, lysine is a strong allosteric inhibitor of Lys21p (K(i) 0.053 mM), which, in addition, induces positive co-operativity for alpha-ketoglutarate (alpha-KG) binding. Differential lysine inhibition and modulation by alpha-KG of the two isozymes, and the regulation of the intracellular amount of the two isoforms, give rise to an exquisite regulatory system, which balances the rate at which alpha-KG is diverted to lysine biosynthesis or to other metabolic pathways. It can thus be concluded that retention and further biochemical specialization of the LYS20- and LYS21-encoded enzymes with partially overlapping roles contributed to the acquisition of facultative metabolism.

Study of electronic and magnetic properties of h-BN on Ni surfaces: A DFT approach

NASA Astrophysics Data System (ADS)

Sahoo, M. R.; Sahu, S.; Kushwaha, A. K.; Nayak, S.

2018-04-01

Hexagonal boron nitride (h-BN) is a promising material for implementation in spintronics due to large band gap, low spin-orbit coupling, and a small lattice mismatch to graphene and close-packedsurfaces of fcc-Ni(111). Electronic and magnetic properties of single layer hexagonal Boron Nitride (h-BN) on Ni (111) surface have been studied with density functional calculation. Since lattice constants of nickel surfaces are very close to that of h-BN, nickel acts as a good substrate. We found that the interaction between 2Pz - 3dz2 orbitals leads to change in electronic band structure as well as density of states which results spin polarization in h-BN.

Analysis of Two in Planta Expressed LysM Effector Homologs from the Fungus Mycosphaerella graminicola Reveals Novel Functional Properties and Varying Contributions to Virulence on Wheat1[W][OA

PubMed Central

Marshall, Rosalind; Kombrink, Anja; Motteram, Juliet; Loza-Reyes, Elisa; Lucas, John; Hammond-Kosack, Kim E.; Thomma, Bart P.H.J.; Rudd, Jason J.

2011-01-01

Secreted effector proteins enable plant pathogenic fungi to manipulate host defenses for successful infection. Mycosphaerella graminicola causes Septoria tritici blotch disease of wheat (Triticum aestivum) leaves. Leaf infection involves a long (approximately 7 d) period of symptomless intercellular colonization prior to the appearance of necrotic disease lesions. Therefore, M. graminicola is considered as a hemibiotrophic (or necrotrophic) pathogen. Here, we describe the molecular and functional characterization of M. graminicola homologs of Ecp6 (for extracellular protein 6), the Lysin (LysM) domain-containing effector from the biotrophic tomato (Solanum lycopersicum) leaf mold fungus Cladosporium fulvum, which interferes with chitin-triggered immunity in plants. Three LysM effector homologs are present in the M. graminicola genome, referred to as Mg3LysM, Mg1LysM, and MgxLysM. Mg3LysM and Mg1LysM genes were strongly transcriptionally up-regulated specifically during symptomless leaf infection. Both proteins bind chitin; however, only Mg3LysM blocked the elicitation of chitin-induced plant defenses. In contrast to C. fulvum Ecp6, both Mg1LysM and Mg3LysM also protected fungal hyphae against plant-derived hydrolytic enzymes, and both genes show significantly more nucleotide polymorphism giving rise to nonsynonymous amino acid changes. While Mg1LysM deletion mutant strains of M. graminicola were fully pathogenic toward wheat leaves, Mg3LysM mutant strains were severely impaired in leaf colonization, did not trigger lesion formation, and were unable to undergo asexual sporulation. This virulence defect correlated with more rapid and pronounced expression of wheat defense genes during the symptomless phase of leaf colonization. These data highlight different functions for MgLysM effector homologs during plant infection, including novel activities that distinguish these proteins from C. fulvum Ecp6. PMID:21467214

What's Going on Around BN

NASA Technical Reports Server (NTRS)

Erickson, Edwin; Colgan, S. W. J.; Schultz, A. S. B.; Simpson, J. P.; Burton, M. G.; Kaufman, M. J.; Young, E. T.; Stolovy, S.

2005-01-01

The Becklin-Neugebauer object, discovered in observations made by Eric Becklin as a graduate student, is the brightest mid-infrared source outside the solar system, and a beacon in the nearest region of massive star formation. Using NICMOS on HST, we have obtained near infrared photometric, spectroscopic, and polarimetric images of the region immediately around BN. These images, with resolutions < -0.2", reveal remarkable morphologies, shock details, new young stellar objects, faint stars with variable intensities, and outflow features. We will summarize these results and inferences regarding the shock properties, illuminating sources of the nebulosity, and IRc sources near BN.

Selection of lys2 Mutants of the Yeast SACCHAROMYCES CEREVISIAE by the Utilization of α-AMINOADIPATE

PubMed Central

Chattoo, Bharat B.; Sherman, Fred; Azubalis, Dalia A.; Fjellstedt, Thorsten A.; Mehnert, David; Ogur, Maurice

1979-01-01

Normal strains of Saccharomyces cerevisiae do not use α-aminoadipate as a principal nitrogen source. However, α-aminoadipate is utilized as a nitrogen source by lys2 and lys5 strains having complete or partial deficiencies of α-aminoadipate reductase and, to a limited extent, by heterozygous lys2/+ strains. Lys2 mutants were conveniently selected on media containing α-aminoadipate as a nitrogen source, lysine, and other supplements to furnish other possible auxotrophic requirements. The lys2 mutations were obtained in a variety of laboratory strains containing other markers, including other lysine mutations. In addition to the predominant class of lys2 mutants, low frequencies of lys5 mutants and mutants not having any obvious lysine requirement were recovered on α-aminoadipate medium. The mutants not requiring lysine appeared to have mutations at the lys2 locus that caused partial deficiencies of α-aminoadipate reductase. Such partial deficiencies are believed to be sufficiently permissive to allow lysine biosynthesis, but sufficiently restrictive to allow for the utilization of α-aminoadipate. Although it is unknown why partial or complete deficiencies of α-aminoadipate reductase cause utilization of α-aminoadipate as a principal nitrogen source, the use of α-aminoadipate medium has considerable utility as a selective medium for lys2 and lys5 mutants. PMID:17248969

Side-gate modulation effects on high-quality BN-Graphene-BN nanoribbon capacitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yang; Chen, Xiaolong; Ye, Weiguang

High-quality BN-Graphene-BN nanoribbon capacitors with double side-gates of graphene have been experimentally realized. The double side-gates can effectively modulate the electronic properties of graphene nanoribbon capacitors. By applying anti-symmetric side-gate voltages, we observed significant upward shifting and flattening of the V-shaped capacitance curve near the charge neutrality point. Symmetric side-gate voltages, however, only resulted in tilted upward shifting along the opposite direction of applied gate voltages. These modulation effects followed the behavior of graphene nanoribbons predicted theoretically for metallic side-gate modulation. The negative quantum capacitance phenomenon predicted by numerical simulations for graphene nanoribbons modulated by graphene side-gates was not observed,more » possibly due to the weakened interactions between the graphene nanoribbon and side-gate electrodes caused by the Ga{sup +} beam etching process.« less

Electronic Properties of Curved and Defective 2-D BN Nanostructures

NASA Astrophysics Data System (ADS)

Beach, Kory; Terrones, Humberto; Raeliarijaona, Aldo; Siegel, Ross; Florio, Fred

Density functional theory (DFT) with local density approximation (LDA) pseudopotentials is used to calculate the band structure and density of states of various novel 2-D BN nanostructures. Three types of systems are studied: Schwarzites, a Haeckelite, and an h-BN monolayer. Schwarzites are negatively curved structures in which the curvature is due to the introduction of octagonal rings of alternating boron and nitrogen atoms. In particular, three families of Schwarzites are analyzed: P, G and IWP. The Haeckelites on the other hand, are flat layers composed of squares and octagons of BN. It is found that all these BN allotropes are metastable in which the band gap is direct and smaller than the most stable system, h-BN. National Science Foundation (EFRI-1433311).

Investigation of structure and mechanical properties of plasma vapor deposited nanocomposite TiBN films

NASA Astrophysics Data System (ADS)

Han, Bin; Neena, D.; Wang, Zesong; Kondamareddy, K. k.; Li, Na; Zuo, Wenbin; Yan, Shaojian; Liu, Chuansheng; Fu, Dejun

2017-04-01

TiBN coatings have huge potential applications as they have excellent properties with increasing modern industrial requirements. Nanocomposite TiBN coatings were synthesized on cemented carbide, high speed steel and Si substrates by using cathodic arc plasma ion plating from pure TiB2 ceramic targets. The structure and mechanical properties of the TiBN coatings were significantly influenced by the nitrogen partial pressure. Rutherford backscattering spectrometry demonstrates that the nitrogen content of the coating varied from 2.8% to 34.5% and high-resolution electron microscopy images reveal that all coatings have the characteristic of nanocrystals embedded in an amorphous matrix. The root-mean-square roughness of the coatings increases from 3.73 to 14.64 nm and the coefficients of friction of the coatings at room temperature vary from 0.54 to 0.73 with increasing nitrogen partial pressure. The microhardness of the coating increases up to 35.7 GPa at 10 sccm N2 flow rate. The smallest wear rate is 2.65 × 10-15 m3 N-1 m-1 which indicates that TiBN coatings have excellent wear resistance. The adhesion test revealed that the TiBN coatings have good adhesion at low nitrogen partial pressure.

Initial Evaluation of (99m)Tc(CO)3(ASMA) as a Renal Tracer in Healthy Human Volunteers.

PubMed

Lipowska, Malgorzata; Klenc, Jeffrey; Folks, Russell D; Taylor, Andrew T

2014-09-01

Preclinical studies in rats showed that two of (99m)Tc(CO)3(ASMA) isomers (rac- and L-ASMA) had pharmacokinetic properties equivalent to that of (131)I-OIH, the radiopharmaceutical standard for the measurement of effective renal plasma flow. The aim of this study was to evaluate the pharmacokinetics of (99m)Tc(CO)3(ASMA) isomers in healthy human subjects. Three ASMA ligands (rac-, L- and D-ASMA) were labeled with (99m)Tc(CO)3 using an IsoLink kit (Covidien), and each formed (99m)Tc(CO)3(ASMA) tracer was co-injected with (131)I-OIH into healthy human subjects followed by sequential imaging, plasma clearance measurements and timed urine collection. Plasma protein binding, red cell uptake and percent injected dose in the urine were determined. Urine from each group of volunteers was analyzed for metabolites by HPLC. Image quality was excellent with all three agents. Each (99m)Tc(CO)3(ASMA) preparation was excreted unchanged in the urine. The plasma clearance ratio ((99m)Tc(CO)3(ASMA)/(131)I-OIH) was 81 ± 3 % for D-ASMA compared to only 20 ± 4 % for L-ASMA and 37 ± 7 % for rac-ASMA; the 81 % clearance ratio for D-ASMA isomer is still ∼ 30 % higher than the (99m)Tc-MAG3/(131)I-OIH clearance ratio (∼50-60 %). Red cell uptake was similar for all three tracers (6-9 %), and all tracers had a relatively rapid renal excretion; at 3 h, the (99m)Tc(CO)3(ASMA)/(131)I-OIH urine ratio was 100 ± 3 % for D-ASMA, 80 ± 2 % for L-ASMA and 88 ± 1 % for rac-ASMA. The renal excretion characteristics of (99m)Tc(CO)3(D-ASMA) in humans are superior to those of the other two (99m)Tc(CO)3(ASMA) isomers studied, but are still inferior to (131)I-OIH, even though there was no difference in the clearance of two of (99m)Tc(CO)3(ASMA) isomers and (131)I-OIH in rats. The work described here demonstrates the sensitivity in in vivo biological behavior of (99m)Tc(CO)3(ASMA) isomers to their subtle structural differences.

78 FR 38544 - Airworthiness Directives; B-N Group Ltd. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-27

... Airworthiness Directives; B-N Group Ltd. Airplanes AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT). ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for all B-N... adding the following new AD: 2013-13-02 B-N Group Ltd.: Amendment 39-17490; Docket No. FAA-2013- 0314...

Intratumoral Injection of 188Re labeled Cationic Polyethylenimine Conjugates: A Preliminary Report

PubMed Central

Kim, Eun-Mi; Heo, Young-Jun; Moon, Hyung-Bae; Bom, Hee-Seung; Kim, Chang-Guhn

2004-01-01

188Re(Rhenium) is easily obtained from an in-house 188W/188Re generator that is similar to the current 99Mo/99mTc generator, making it very convenient for clinical use. This characteristic makes this radionuclide a promising candidate as a therapeutic agent. Polyethylenimine (PEI) is a cationic polymer and has been used as a gene delivery vector. Positively charged materials interact with cellular blood components, vascular endothelium, and plasma proteins. In this study, the authors investigated whether intratumoral injection of 188Re labeled transferrin (Tf)-PEI conjugates exert the effect of radionuclide therapy against the tumor cells. When the diameters of the Ramos lymphoma (human Burkitt's lymphoma) xenografted tumors reached approximately 1 cm, 3 kinds of 188Re bound compounds (HYNIC-PEI-Tf, HYNIC-PEI, 188Re perrhenate) were injected directly into the tumors. There were increases in the retention of 188Re inside the tumor when PEI was incorporated with 188Re compared to the use of free 188Re. The 188Re HYNIC-Tf-PEI showed the most retention inside the tumor (retention rate=approximately 97%). H&E stain of isolated tumor tissues showed that 188Re labeled HYNIC-PEI-Tf caused extensive tumor necrosis. These results support 188Re HYNIC-PEI-Tf as being a useful radiopharmaceutical agent to treat tumors when delievered by intratumoral injection. PMID:15483337

In situ synthesis of Fe-based alloy clad coatings containing TiB2-TiN-(h-BN)

NASA Astrophysics Data System (ADS)

Jiang, Shao-qun; Wang, Gang; Ren, Qing-wen; Yang, Chuan-duo; Wang, Ze-hua; Zhou, Ze-hua

2015-06-01

Fe-based alloy coatings containing TiB2-TiN-(h-BN) were synthesized in situ on Q235 steel substrates by a plasma cladding process using the powders of Fe901 alloy, Ti, and h-BN as raw materials. The effects of Ti/h-BN mass ratio on interfacial bonds between the coating and substrate along with the microstructures and microhardnesses of the coatings were investigated. The results show that the Ti/h-BN mass ratio is a vital factor in the formation of the coatings. Free h-BN can be introduced into the coatings by adding an excess amount of h-BN into the precursor. Decreases in the Ti/h-BN mass ratio improve the microstructural uniformity and compactness and enhance the interfacial bonds of the coatings. At a Ti/h-BN mass ratio of 10/20, the coating is free of cracks and micropores, and mainly consists of Fe-Cr, Fe3B, TiB2, TiN, Ti2N, TiB, FeN, FeB, Fe2B, and h-BN phases. Its average microhardness in the zone between 0.1-2.8 mm from the coating surface is about Hv0.2 551.5.

Investigation on two abnormal phenomena about thermal conductivity enhancement of BN/EG nanofluids.

PubMed

Li, Yanjiao; Zhou, Jing'en; Luo, Zhifeng; Tung, Simon; Schneider, Eric; Wu, Jiangtao; Li, Xiaojing

2011-07-09

The thermal conductivity of boron nitride/ethylene glycol (BN/EG) nanofluids was investigated by transient hot-wire method and two abnormal phenomena was reported. One is the abnormal higher thermal conductivity enhancement for BN/EG nanofluids at very low-volume fraction of particles, and the other is the thermal conductivity enhancement of BN/EG nanofluids synthesized with large BN nanoparticles (140 nm) which is higher than that synthesized with small BN nanoparticles (70 nm). The chain-like loose aggregation of nanoparticles is responsible for the abnormal increment of thermal conductivity enhancement for the BN/EG nanofluids at very low particles volume fraction. And the difference in specific surface area and aspect ratio of BN nanoparticles may be the main reasons for the abnormal difference between thermal conductivity enhancements for BN/EG nanofluids prepared with 140- and 70-nm BN nanoparticles, respectively.

Overexpression of BnWRKY33 in oilseed rape enhances resistance to Sclerotinia sclerotiorum.

PubMed

Wang, Zheng; Fang, Hedi; Chen, Yu; Chen, Keping; Li, Guanying; Gu, Shoulai; Tan, Xiaoli

2014-09-01

Sclerotinia sclerotiorum causes a devastating disease in oilseed rape (Brassica napus) resulting in a tremendous yield loss worldwide. Studies on various host-pathogen interactions have shown that plant WRKY transcription factors are essential for defence. For the B. napus-S. sclerotiorum interaction, little direct evidence has been found with regard to the biological roles of specific WRKY genes in host resistance. In this study, we isolated a B. napus WRKY gene, BnWRKY33, and found that the gene is highly responsive to S. sclerotiorum infection. Transgenic B. napus plants overexpressing BnWRKY33 showed markedly enhanced resistance to S. sclerotiorum, constitutive activation of the expression of BnPR1 and BnPDF1.2, and inhibition of H2 O2 accumulation in response to pathogen infection. Further, we isolated a mitogen-activated protein (MAP) kinase substrate gene, BnMKS1, and found that not only can BnWRKY33 interact with BnMKS1, which can also interact with BnMPK4, using the yeast two-hybrid assay, consistent with their collective nuclear localization, but also BnWRKY33, BnMKS1 and BnMPK4 are substantially and synergistically expressed in response to S. sclerotiorum infection. In contrast, the three genes showed differential expression in response to phytohormone treatments. Together, these results suggest that BnWRKY33 plays an important role in B. napus defence to S. sclerotiorum, which is most probably associated with the activation of the salicylic acid (SA)- and jasmonic acid (JA)-mediated defence response and inhibition of H2 O2 accumulation, and we propose a potential mechanism in which BnMPK4-BnMKS1-BnWRKY33 exist in a nuclear localized complex to regulate resistance to S. sclerotiorum in oilseed rape. © 2014 BSPP AND JOHN WILEY & SONS LTD.

Wafer scale BN on sapphire substrates for improved graphene transport.

PubMed

Vangala, Shivashankar; Siegel, Gene; Prusnick, Timothy; Snure, Michael

2018-06-11

Wafer scale (2") BN grown by metal organic chemical vapor deposition (MOCVD) on sapphire was examined as a weakly interacting dielectric substrate for graphene, demonstrating improved transport properties over conventional sapphire and SiO 2 /Si substrates. Chemical vapor deposition grown graphene was transferred to BN/sapphire substrates for evaluation of more than 30 samples using Raman and Hall effects measurements. A more than 2x increase in Hall mobility and 10x reduction in sheet carrier density was measured for graphene on BN/sapphire compared to sapphire substrates. Through control of the MOCVD process, BN films with roughness ranging from <0.1 nm to >1 nm were grown and used to study the effects of substrate roughness on graphene transport. Arrays of graphene field effect transistors were fabricated on 2" BN/sapphire substrates demonstrating scalability and device performance enhancement.

Molecular dynamics simulations of human tRNA Lys,3 UUU: the role of modified bases in mRNA recognition.

PubMed

McCrate, Nina E; Varner, Mychel E; Kim, Kenneth I; Nagan, Maria C

2006-01-01

Accuracy in translation of the genetic code into proteins depends upon correct tRNA-mRNA recognition in the context of the ribosome. In human tRNA(Lys,3)UUU three modified bases are present in the anticodon stem-loop--2-methylthio-N6-threonylcarbamoyladenosine at position 37 (ms2t6A37), 5-methoxycarbonylmethyl-2-thiouridine at position 34 (mcm5s2U34) and pseudouridine (psi) at position 39--two of which, ms2t6A37 and mcm5s2U34, are required to achieve wild-type binding activity of wild-type human tRNA(Lys,3)UUU [C. Yarian, M. Marszalek, E. Sochacka, A. Malkiewicz, R. Guenther, A. Miskiewicz and P. F. Agris (2000) Biochemistry, 39, 13390-13395]. Molecular dynamics simulations of nine tRNA anticodon stem-loops with different combinations of nonstandard bases were performed. The wild-type simulation exhibited a canonical anticodon stair-stepped conformation. The ms2t6 modification at position 37 is required for maintenance of this structure and reduces solvent accessibility of U36. Ms2t6A37 generally hydrogen bonds across the loop and may prevent U36 from rotating into solution. A water molecule does coordinate to psi39 most of the simulation time but weakly, as most of the residence lifetimes are <40 ps.

Effect of substrate temperature and gas flow ratio on the nanocomposite TiAlBN coating

NASA Astrophysics Data System (ADS)

Rosli, Z. M.; Kwan, W. L.; Juoi, J. M.

2016-07-01

Nanocomposite TiAlBN (nc-TiAlBN) coatings were successfully deposited via RF magnetron sputtering by varying the nitrogen-to-total gas flow ratio (RN), and substrate temperature (TS). All coatings were deposited on AISI 316 substrates using single Ti-Al-BN hot-pressed disc as a target. The grain size, phases, and chemical composition of the coatings were evaluated using glancing angle X-ray diffraction analysis (GAXRD) and X-ray photoelectron spectroscopy (XPS). Results showed that the grains size of the deposited nc-TiAlBN coatings were in the range of 3.5 to 5.7 nm and reached a nitride saturation state as early as 15 % RN. As the nitrogen concentration decreases, boron concentration increased from 9 at.% to 16.17 at.%. and thus, increase the TiB2 phase within the coatings. The TS, however, showed no significant effect either on the crystallographic structure, grain size, or in the chemical composition of the deposited nc-TiAlBN coating.

Early detection of rheumatoid arthritis in rats and humans with 99mTc-3PRGD2 scintigraphy: imaging synovial neoangiogenesis.

PubMed

Wu, Yu; Zhang, Guojian; Wang, Xiangcheng; Zhao, Zhenfang; Wang, Tao; Wang, Xuemei; Li, Xiao-Feng

2017-01-24

To validate 99mTc-labeled arginylglycylaspartic acid (99mTc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis. Rheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99mTc-3PRGD2 and 99mTc- methyl diphosphonate (99mTc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of αvβ3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99mTc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99mTc-3PRGD2. Two weeks after immunization, a significant increase in 99mTc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99mTc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of αvβ3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99mTc-3PRGD2 scintigraphy studies, 99mTc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99mTc-3PRGD2 uptake. Significantly higher 99mTc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient. Our findings indicate that 99mTc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management.

A comparative DFT study on the interaction of cathinone drug with BN nanotubes, nanocages, and nanosheets

NASA Astrophysics Data System (ADS)

Nejati, Kamellia; Hosseinian, Akram; Vessally, Esmail; Bekhradnia, Ahmadreza; Edjlali, Ladan

2017-11-01

Cathinone is an organic stimulant which is classified as psychoactive drug and its abuse has been linked to many deaths worldwide. Here, we studied the electronic sensitivity of a BN cage, a zigzag (6, 0) BN nanotube, and a BN nanosheet toward cathinone using density functional theory calculations. The B3LYP-D functional predicts that the order of magnitude of electrical conductivity of BN nanostructures is as follows tube > sheet > cage. The cathinone drug prefers to be adsorbed on the BN nanostructures via its sbnd NH2 group rather than O-head with adsorption energy about -16.1, -14.0 and -5.0 kcal/mol for cage, tube, and sheet, respectively. Our results indicate that by increasing the p-character of the hybridization of the adsorbing B atom in the BN nanostructures, the interaction is strengthened. Based on the density of states analysis, it was demonstrated that the electrical conductivity of the BN nanostructures is decreased by the drug adsorption, indicating that they can be used in the cathinone sensors. The order of magnitude of the sensitivity is as follows: SCage > STube > SSheet. This trend corresponds to the decrease of the structural curvature in the BN nanostructures. Finally, a short recovery time of about 0.54 s, 0.02 s and 4.4 ns is predicted for cage, tube and sheet, respectively, at 298 K.

Effects of hydrostatic pressure and biaxial strains on the elastic and electronic properties of t-C8B2N2

NASA Astrophysics Data System (ADS)

Zhu, Haiyan; Shi, Liwei; Li, Shuaiqi; Duan, Yifeng; Zhang, Shaobo; Xia, Wangsuo

2018-04-01

The effects of hydrostatic pressure and biaxial strains on the elastic and electronic properties of a superhard material t-C8B2N2 have been studied using first-principles calculations. The structure is proven to be mechanically and dynamically stable under the applied external forces. All the elastic constants (except C66) and elastic modulus increase (decrease) with increasing pressure and compressive (tensile) biaxial strain ɛxx. A microscopic model is used to calculate the Vicker's hardness of every single bond as well as the crystal. The hardness of t-C8B2N2 (64.7 GPa) exceeds that of c-BN (62 GPa) and increases obviously by employing pressure and compressive ɛxx. Furthermore, the Debye temperature and anisotropy of sound velocities for t-C8B2N2 have been discussed. t-C8B2N2 undergoes an indirect to direct bandgap transition when ɛxx > 2%; however, the indirect bandgap character of the material remains under pressure.

Deposition Of Cubic BN On Diamond Interlayers

NASA Technical Reports Server (NTRS)

Ong, Tiong P.; Shing, Yuh-Han

1994-01-01

Thin films of polycrystalline, pure, cubic boron nitride (c-BN) formed on various substrates, according to proposal, by chemical vapor deposition onto interlayers of polycrystalline diamond. Substrate materials include metals, semiconductors, and insulators. Typical substrates include metal-cutting tools: polycrystalline c-BN coats advantageous for cutting ferrous materials and for use in highly oxidizing environments-applications in which diamond coats tend to dissolve in iron or be oxidized, respectively.

In vitro and in vivo evaluation of a 64Cu-labeled NOTA-Bn-SCN-Aoc-bombesin analogue in gastrin-releasing peptide receptor expressing prostate cancer.

PubMed

Craft, Jeffrey M; De Silva, Ravindra A; Lears, Kimberly A; Andrews, Rebecca; Liang, Kexian; Achilefu, Samuel; Rogers, Buck E

2012-07-01

Bombesin (BN) is an amphibian peptide that binds to the gastrin-releasing peptide receptor (GRPR). It has been demonstrated that BN analogues can be radiolabeled for potential diagnosis and treatment of GRPR-expressing malignancies. Previous studies have conjugated various chelators to the eight C-terminal amino acids of BN [BN(7-14)] for radiolabeling with 64Cu. Recently, (1,4,7-triazacyclononane-1,4,7-triacetic acid) (NOTA) has been evaluated as the five-coordinate 64Cu complex, with results indicating GRPR-specific tumor uptake. This study aimed to conjugate S-2-(4-isothiocyanatobenzyl)-NOTA (p-SCN-Bn-NOTA) to BN(7-14) such that it could form a six-coordinate complex with 64Cu and to evaluate the resulting peptide. p-SCN-NOTA was conjugated to 8-aminooctanoic acid (Aoc)-BN(7-14) in solution to yield NOTA-Bn-SCN-Aoc-BN(7-14). The unlabeled peptide was evaluated in a cell binding assay using PC-3 prostate cancer cells and 125I-Tyr4-BN to determine the IC50 value. The peptide was radiolabeled with 64Cu and evaluated for internalization into PC-3 cells and for tumor uptake in mice bearing PC-3 xenografts using biodistribution and micro-positron emission tomography imaging studies. The binding assay demonstrated that NOTA-Bn-SCN-Aoc-BN(7-14) bound with high affinity to GRPR with an IC50 of 1.4 nM. The radiolabeled peptide demonstrated time-dependent internalization into PC-3 cells. In vivo, the peptide demonstrated tumor-specific uptake and imaging that were comparable to those of previously reported 64Cu-labeled BN analogues. These studies demonstrate that 64Cu-NOTA-Bn-SCN-Aoc-BN(7-14) binds to GRPR-expressing cells and that it can be used for imaging of GRPR-expressing prostate cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Leptin receptor Lys656Asn polymorphism is associated with decreased leptin response and weight loss secondary to a lifestyle modification in obese patients.

PubMed

de Luis Roman, Daniel; de la Fuente, Rocio Aller; Sagrado, Manuel Gonzalez; Izaola, Olatz; Vicente, Rosa Conde

2006-10-01

Human obesity is characterized by high levels of leptin, and it has been suggested that obese patients may be leptin resistant. The aim of our study was to investigate the influence of Lys656Asn polymorphism in the leptin receptor gene on leptin response and weight loss secondary to a lifestyle modification (Mediterranean hypocaloric diet and exercise) in obese patients. A population of 67 obese (body mass index >30) nondiabetic outpatients was analyzed in a prospective way. Before and after 3 months of lifestyle modification program, bipolar electrical bioimpedance, blood pressure, and a serial assessment of nutritional intake with 3 days written food records and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1520 kcal, 52% carbohydrates, 25% lipids and 23% proteins). The exercise program consisted of aerobic exercise for at least three times per week (60 min each). Statistical analysis was performed for the combined Lys656/Asn656 and Asn656/Asn656 as mutant group and type Lys656/Lys 656 as wild-type second group. Sixty seven patients gave informed consent and were enrolled in the study. The mean age was 45.7 +/- 16.6 years and the mean BMI 34.1 +/- 5.1, with 18 males (26.9%) and 49 females (73.1%). Thirty six patients (10 males/26 females) (46.8%) had the genotype Lys656/Lys 656 (wild-type group) and 31 patients (8 males/23 females) (46.3%) Lys656/Asn656 (n = 28, 41.8%) or Asn656/Asn656 (n = 3, 4.5%) (mutant group). The percentage of responders (weight loss) was similar in both groups (91.7 vs. 87.1%). In wild-type group (responders and nonresponders), BMI, weight, fat mass, systolic blood pressure and waist circumference decreased. In mutant group, BMI, weight and waist circumference decreased. No differences were detected between basal values in both groups. Only leptin levels decreased significantly in wild-type group (11.5%; p <0.05) (57.3 +/- 31.5 ng/mL vs. 45.8 +/- 29.3 ng/mL; p <0.05). In mutant

Theoretical analysis of nBn infrared photodetectors

NASA Astrophysics Data System (ADS)

Ting, David Z.; Soibel, Alexander; Khoshakhlagh, Arezou; Gunapala, Sarath D.

2017-09-01

The depletion and surface leakage dark current suppression properties of unipolar barrier device architectures such as the nBn have been highly beneficial for III-V semiconductor-based infrared detectors. Using a one-dimensional drift-diffusion model, we theoretically examine the effects of contact doping, minority carrier lifetime, and absorber doping on the dark current characteristics of nBn detectors to explore some basic aspects of their operation. We found that in a properly designed nBn detector with highly doped excluding contacts the minority carriers are extracted to nonequilibrium levels under reverse bias in the same manner as the high operating temperature (HOT) detector structure. Longer absorber Shockley-Read-Hall (SRH) lifetimes result in lower diffusion and depletion dark currents. Higher absorber doping can also lead to lower diffusion and depletion dark currents, but the benefit should be weighted against the possibility of reduced diffusion length due to shortened SRH lifetime. We also briefly examined nBn structures with unintended minority carrier blocking barriers due to excessive n-doping in the unipolar electron barrier, or due to a positive valence band offset between the barrier and the absorber. Both types of hole blocking structures lead to higher turn-on bias, although barrier n-doping could help suppress depletion dark current.

Stabilization of the O p2x2 phase on Cu(001) sheltered by wrinkled BN over-layer

NASA Astrophysics Data System (ADS)

Kim, Yong-Sung; Ma, Chuanxu; Li, An-Ping; Yoon, Mina

The 2 √3x √3R45°phase of oxygen (O) on the Cu(001) surface has been observed in scanning tunneling microscopy (STM) measurements. Although the p2x2 phase of O on the Cu(001) surface has been proposed theoretically to be the most stable in O-lean conditions, it has not been observed in experiments for a long time. Recently, the O p2x2 phase has been found in STM on the Cu(001) surface with an overlying BN monolayer. In this theoretical study, we investigate what the role of BN over-layer is to stabilize the O p2x2 phase on the Cu(001) surface. The BN over-layer is lattice-matched with the Cu(001) surface and the BN mono-layer sheet is periodically wrinkled along the BN arm-chair direction and along the [100] or [010] direction on the Cu(001) surface. The interlayer space between the Cu(001) surface and the bulge of the wrinkled BN sheet is found to play as a preferential shelter for O to be adsorbed, and the boundary of the BN inner wall along the [010] or [100] direction makes the p2x2 phase more favorable against the 45°-tilted 2 √3x √3R45°phase of O on the Cu(001) surface. This was supported by Center for Nanophase Materials Sciences, which is a DOE Office of Science User Facility, and the Laboratory Directed Research and Development Program of Oak Ridge National Laboratory, maaged by UT-Battelle, LLC, for the U. S. DOE.

Microstructures of BN/SiC coatings on nicalon fibers

NASA Technical Reports Server (NTRS)

Dickerson, R. M.; Singh, M.

1995-01-01

The microstructures of Nicalon silicon carbide (SiC) fibers and layered coatings of boron nitride (BN) followed by chemical vapor infiltrated silicon carbide (CVI-SiC) were characterized using optical and electron microscopy. Two different precursors and reactions were used to produce the BN layers while the deposition of CVI silicon carbide was nearly identical. Coated tows were examined in cross-section to characterize the chemistry and structures of the constituents and the interfaces. One BN precursor yielded three sublayers while the other gave a relatively homogeneous nanocrystalline layer.

Early detection of rheumatoid arthritis in rats and humans with 99mTc-3PRGD2 scintigraphy: imaging synovial neoangiogenesis

PubMed Central

Wang, Xiangcheng; Zhao, Zhenfang; Wang, Tao; Wang, Xuemei; Li, Xiao-Feng

2017-01-01

Objectives: To validate 99mTc-labeled arginylglycylaspartic acid (99mTc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis. Methods: Rheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99mTc-3PRGD2 and 99mTc- methyl diphosphonate (99mTc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of αvβ3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99mTc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99mTc-3PRGD2. Results: Two weeks after immunization, a significant increase in 99mTc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99mTc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of αvβ3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99mTc-3PRGD2 scintigraphy studies, 99mTc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99mTc-3PRGD2 uptake. Significantly higher 99mTc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient. Conclusions: Our findings indicate that 99mTc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management. PMID:27992368

Thermal Conductivity of Epoxy Resin Composites Filled with Combustion Synthesized h-BN Particles.

PubMed

Chung, Shyan-Lung; Lin, Jeng-Shung

2016-05-20

The thermal conductivity of epoxy resin composites filled with combustion-synthesized hexagonal boron nitride (h-BN) particles was investigated. The mixing of the composite constituents was carried out by either a dry method (involving no use of solvent) for low filler loadings or a solvent method (using acetone as solvent) for higher filler loadings. It was found that surface treatment of the h-BN particles using the silane 3-glycidoxypropyltrimethoxysilane (GPTMS) increases the thermal conductivity of the resultant composites in a lesser amount compared to the values reported by other studies. This was explained by the fact that the combustion synthesized h-BN particles contain less -OH or active sites on the surface, thus adsorbing less amounts of GPTMS. However, the thermal conductivity of the composites filled with the combustion synthesized h-BN was found to be comparable to that with commercially available h-BN reported in other studies. The thermal conductivity of the composites was found to be higher when larger h-BN particles were used. The thermal conductivity was also found to increase with increasing filler content to a maximum and then begin to decrease with further increases in this content. In addition to the effect of higher porosity at higher filler contents, more horizontally oriented h-BN particles formed at higher filler loadings (perhaps due to pressing during formation of the composites) were suggested to be a factor causing this decrease of the thermal conductivity. The measured thermal conductivities were compared to theoretical predictions based on the Nielsen and Lewis theory. The theoretical predictions were found to be lower than the experimental values at low filler contents (< 60 vol %) and became increasing higher than the experimental values at high filler contents (> 60 vol %).

Toward organometallic (99m)Tc imaging agents: synthesis of water-stable (99)Tc-NHC complexes.

PubMed

Benz, Michael; Spingler, Bernhard; Alberto, Roger; Braband, Henrik

2013-11-20

(99)Tc(V)O2-NHC complexes containing monodentate and bidentate N-heterocyclic carbenes (NHCs) have been prepared by the reactions of [TcO(glyc)2](-) (glyc = ethyleneglycolato) with 1,3-dimethylimidazoline-2-ylidene (L1), 1,1'-methylene-3,3'-dimethyl-4,4'-diimidazoline-2,2'-diylidene (L2), and 1,1'-methylene-3,3'-diethyl-4,4'-diimidazoline-2,2'-diylidene (L3) in THF. The resulting complexes were fully characterized and their stabilities investigated. While complexes with monodentate NHCs only are hydrolytically unstable, complexes containing bidentate NHCs are water-stable over a broad pH range. The high water stability allows interconversion of the {(99)Tc(V)O2}(+) core into {(99)Tc(V)OCl}(2+) with HCl as the H(+) and Cl(-) source. An alternative procedure to obtain (99)Tc(V)O2-NHC complexes is the in situ deprotonation of imidazolium salts, enabling the preparation of (99)Tc(V)O2-NHC compounds without free NHCs, thus increasing the scope of NHC ligands drastically. The remarkable stability and pH-controllable reactivity of the new complexes underlines the potential of NHCs as stabilizing ligands for (99)Tc complexes and paves the way for the first (99m)Tc-NHC complexes in the future.

Electron Excess Doping and Effective Schottky Barrier Reduction on the MoS2/h-BN Heterostructure.

PubMed

Joo, Min-Kyu; Moon, Byoung Hee; Ji, Hyunjin; Han, Gang Hee; Kim, Hyun; Lee, Gwanmu; Lim, Seong Chu; Suh, Dongseok; Lee, Young Hee

2016-10-12

Layered hexagonal boron nitride (h-BN) thin film is a dielectric that surpasses carrier mobility by reducing charge scattering with silicon oxide in diverse electronics formed with graphene and transition metal dichalcogenides. However, the h-BN effect on electron doping concentration and Schottky barrier is little known. Here, we report that use of h-BN thin film as a substrate for monolayer MoS 2 can induce ∼6.5 × 10 11 cm -2 electron doping at room temperature which was determined using theoretical flat band model and interface trap density. The saturated excess electron concentration of MoS 2 on h-BN was found to be ∼5 × 10 13 cm -2 at high temperature and was significantly reduced at low temperature. Further, the inserted h-BN enables us to reduce the Coulombic charge scattering in MoS 2 /h-BN and lower the effective Schottky barrier height by a factor of 3, which gives rise to four times enhanced the field-effect carrier mobility and an emergence of metal-insulator transition at a much lower charge density of ∼1.0 × 10 12 cm -2 (T = 25 K). The reduced effective Schottky barrier height in MoS 2 /h-BN is attributed to the decreased effective work function of MoS 2 arisen from h-BN induced n-doping and the reduced effective metal work function due to dipole moments originated from fixed charges in SiO 2 .

Isolation, purification and functional characterization of alpha-BnIA from Conus bandanus venom.

PubMed

Nguyen, Bao; Le Caer, Jean-Pierre; Aráoz, Romulo; Thai, Robert; Lamthanh, Hung; Benoit, Evelyne; Molgó, Jordi

2014-12-01

We report the isolation and characterization by proteomic approach of a native conopeptide, named BnIA, from the crude venom of Conus bandanus, a molluscivorous cone snail species, collected in the South central coast of Vietnam. Its primary sequence was determined by matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry using collision-induced dissociation and confirmed by Edman's degradation of the pure native fraction. BnIA was present in high amounts in the crude venom and the complete sequence of the 16 amino acid peptide was the following GCCSHPACSVNNPDIC*, with C-terminal amidation deduced from Edman's degradation and theoretical monoisotopic mass calculation. Sequence alignment revealed that its -C1C2X4C3X7C4- pattern belongs to the A-superfamily of conopeptides. The cysteine connectivity of BnIA was 1-3/2-4 as determined by partial-reduction technique, like other α4/7-conotoxins, reported previously on other Conus species. Additionally, we found that native α-BnIA shared the same sequence alignment as Mr1.1, from the closely related molluscivorous Conus marmoreus venom, in specimens collected in the same coastal region of Vietnam. Functional studies revealed that native α-BnIA inhibited acetylcholine-evoked currents reversibly in oocytes expressing the human α7 nicotinic acetylcholine receptors, and blocked nerve-evoked skeletal muscle contractions in isolated mouse neuromuscular preparations, but with ∼200-times less potency. Copyright © 2014 Elsevier Ltd. All rights reserved.

Raman spectroscopy and time-resolved photoluminescence of BN and BxCyNz nanotubes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, J.; Han, Wei-Qiang; Walukiewicz, W.

2004-01-21

We report Raman and time-resolved photoluminescence spectroscopic studies of multiwalled BN and B{sub x}C{sub y}N{sub z} nanotubes. The Raman spectroscopy shows that the as-grown B{sub x}C{sub y}N{sub z} charge recombination, respectively. Comparison of the photoluminescence of BN nanotubes to that decay process is characterized by two time constants that are attributed to intra- and inter-BN sheet nanotubes as predicted by theory. nanotubes are radially phase separated into BN shells and carbon shells. The photoluminescence of hexagonal BN is consistent with the existence of a spatially indirect band gap in multi-walled BN.

Acetone in Orion BN/KL. High-resolution maps of a special oxygen-bearing molecule

NASA Astrophysics Data System (ADS)

Peng, T.-C.; Despois, D.; Brouillet, N.; Baudry, A.; Favre, C.; Remijan, A.; Wootten, A.; Wilson, T. L.; Combes, F.; Wlodarczak, G.

2013-06-01

Aims: As one of the prime targets of interstellar chemistry study, Orion BN/KL clearly shows different molecular distributions between large nitrogen- (e.g., C2H5CN) and oxygen-bearing (e.g., HCOOCH3) molecules. However, acetone (CH3)2CO, a special complex O-bearing molecule, has been shown to have a very different distribution from other typical O-bearing molecules in the BN/KL region. Therefore, it is worth investigating acetone in detail at high angular resolutions, which will help us understand the formation of this molecule and its chemical role in the complex BN/KL region. Methods: We searched for acetone within our IRAM Plateau de Bure Interferometer 3 mm and 1.3 mm data sets. Twenty-two acetone lines were searched within these data sets. The angular resolution ranged from 1farcs8×0farcs8 to 6farcs0×2farcs3, and the spectral resolution ranged from 0.4 to 1.9 km s-1. Results: Nine of the acetone lines appear free of contamination. Three main acetone peaks (Ace-1, 2, and 3) are identified in Orion BN/KL. The new acetone source Ace-3 and the extended emission in the north of the hot core region have been found for the first time. An excitation temperature of about 150 K is determined toward Ace-1 and Ace-2, and the acetone column density is estimated to be 2-4 × 1016 cm-2 with a relative abundance of 1-6 × 10-8 toward these two peaks. Acetone is a few times less abundant toward the hot core and Ace-3 compared with Ace-1 and Ace-2. Conclusions: We find that the overall distribution of acetone in BN/KL is similar to that of N-bearing molecules, e.g., NH3 and C2H5CN, and very different from those of large O-bearing molecules, e.g., HCOOCH3 and (CH3)2O. Our findings show the acetone distribution is more extended than in previous studies and does not originate only in those areas where both N-bearing and O-bearing species are present. Moreover, because the N-bearing molecules may be associated with shocked gas in Orion BN/KL, this suggests that the formation and

Crystal structure of LysK, an enzyme catalyzing the last step of lysine biosynthesis in Thermus thermophilus, in complex with lysine: Insight into the mechanism for recognition of the amino-group carrier protein, LysW.

PubMed

Fujita, Satomi; Cho, Su-Hee; Yoshida, Ayako; Hasebe, Fumihito; Tomita, Takeo; Kuzuyama, Tomohisa; Nishiyama, Makoto

2017-09-16

LysK is an M20 peptidase family enzyme that hydrolyzes the isopeptide bond between the carrier protein LysW and lysine in order to release lysine, which is the last step of lysine biosynthesis in Thermus thermophilus. In the present study, we determined the crystal structure of LysK in complex with lysine at a resolution of 2.4 Å. The α-amino group of the bound lysine was oriented toward the catalytic center, which was composed of the residues coordinating divalent metal ions for the hydrolysis of the isopeptide bond. An 11 Å-long path was observed from the active site binding lysine to the protein surface, which may be responsible for recognizing the C-terminal extension domain of LysW with the conserved EDWGE sequence. A positively-charged surface region was detected around the exit of the path, similar to other lysine biosynthetic enzymes using LysW as the carrier protein. Mutational studies of the surface residues provided a plausible model for the electrostatic interaction with LysW. Copyright © 2017 Elsevier Inc. All rights reserved.

Multilayered BN Coatings Processed by a Continuous LPCVD Treatment onto Hi-Nicalon Fibers

NASA Astrophysics Data System (ADS)

Jacques, S.; Vincent, H.; Vincent, C.; Lopez-Marure, A.; Bouix, J.

2001-12-01

Boron nitride coatings were deposited onto SiC fibers by means of continuous low-pressure chemical vapor deposition (LPCVD) treatment from BF3/NH3 mixtures. This process lies in unrolling the fiber in the reactor axis. The relationships between the processing parameters and the structure of the BN deposits are presented. Thanks to a temperature gradient present in the reactor, multilayered BN films can be performed by stacking successive isotropic and anisotropic sublayers. Tensile tests show that when the temperature profile is well adapted, the SiC fibers are not damaged by the LPCVD treatment.

Stability and electronic properties of Gex(BN)y monolayers

NASA Astrophysics Data System (ADS)

Freitas, A.; Machado, L. D.; Tromer, R. M.; Bezerra, C. G.; Azevedo, S.

2017-10-01

In this work, we employ ab initio simulations to propose a new class of monolayers with stoichiometry Gex(BN)y . These monolayers belong to a family of 2D materials combining B, N and group IV atoms, such as BxCyNz and SixByNz . We calculated the formation energy for ten atomic arrangements, and found that it increases when the number of Bsbnd Ge and Nsbnd Ge bonds increases, and decreases when the number of Bsbnd N and Gesbnd Ge bonds increases. We found that the lowest energy monolayer presented a Ge2 BN stoichiometry, and maximized the number of Bsbnd N and Gesbnd Ge bonds. This structure also presented mixed sp2 and sp3 bonds and out-of-plane buckling. Moreover, it remained stable in our ab initio molecular dynamics simulations carried out at T = 300 K. The calculated electronic properties revealed that Gex(BN)y monolayers might present conductor or semiconductor behavior, with band gaps ranging from 0.0 to 0.74 eV, depending on atomic arrangement. Tunable values of band gap can be useful in applications. In optoelectronics, for instance, this property might be employed to control absorbed light wavelengths. Our calculations add a new class of monolayers to the increasing library of 2D materials.

Electronic properties of T graphene-like C-BN sheets: A density functional theory study

NASA Astrophysics Data System (ADS)

Majidi, R.

2015-11-01

We have used density functional theory to study the electronic properties of T graphene-like C, C-BN and BN sheets. The planar T graphene with metallic property has been considered. The results show that the presence of BN has a considerable effect on the electronic properties of T graphene. The T graphene-like C-BN and BN sheets show semiconducting properties. The energy band gap is increased by enhancing the number of BN units. The possibility of opening and controlling band gap opens the door for T graphene in switchable electronic devices.

The electrical and thermal transport properties of hybrid zigzag graphene-BN nanoribbons

NASA Astrophysics Data System (ADS)

Gao, Song; Lu, Wei; Zheng, Guo-Hui; Jia, Yalei; Ke, San-Huang

2017-06-01

The electron and phonon transport in hybrid graphene-BN zigzag nanoribbons are investigated by the nonequilibrium Green’s function method combined with density functional theory calculations. A 100% spin-polarized electron transport in a large energy window around the Fermi level is found and this behavior is independent of the ribbon width as long as there contain 3 zigzag carbon chains. The phonon transport calculations show that the ratio of C-chain number to BN-chain number will modify the thermal conductance of the hybrid nanoribbon in a complicated manner.

Synthesis, Characterization, and In Vitro Evaluation of New (99m)Tc/Re(V)-Cyclized Octreotide Analogues: An Experimental and Computational Approach.

PubMed

Li, Yawen; Ma, Lixin; Gaddam, Vikram; Gallazzi, Fabio; Hennkens, Heather M; Harmata, Michael; Lewis, Michael R; Deakyne, Carol A; Jurisson, Silvia S

2016-02-01

Radiolabeled proteolytic degradation-resistant somatostatin analogues have been of long-standing interest as cancer imaging and radiotherapy agents for targeting somatostatin receptor-positive tumors. Our interest in developing (186)Re- and (188)Re-based therapeutic radiopharmaceuticals led to investigation of a new Re(V)-cyclized octreotide analogue, Re(V)-cyclized, thiolated-DPhe(1)-Cys(2)-Tyr(3)-DTrp(4)-Lys(5)-Thr(6)-Cys(7)-Thr(OH)(8) (Re-SDPhe-TATE) using both experimental and quantum chemical methods. The metal is directly coordinated to SDPhe-TATE through cyclization of the peptide around the [ReO](3+) core. Upon complexation, four isomers were observed; the isolated/semi-isolated isomers exhibited different somatostatin receptor (sstr) binding affinities, 0.13 to 1.5 μM, in rat pancreatic tumor cells. Two-dimensional NMR experiments and electronic structure calculations were employed to elucidate the structural differences among the different isomers. According to NMR studies, the metal is coordinated to three thiolates and the backbone amide of Cys(2) in isomers 1 and 4, whereas the metal is coordinated to three thiolates and the backbone amide of Tyr(3) in isomer 2. Quantum chemical methods clarified the stereochemistry of Re-SDPhe-TATE and the possible peptide arrangements around the [ReO](3+) core. The re-cyclization reaction was translated to the (99m)Tc radiotracer level with four isomers observed on complexation with comparable HPLC retention times as the Re-SDPhe-TATE isomers. About 85% total (99m)Tc labeling yield was achieved by ligand exchange from (99m)Tc-glucoheptonate at 60 °C for an hour. About 100% and 51% of (99m)Tc(V)-cyclized SDPhe-TATE remained intact in phosphate buffered saline and 1 mM cysteine solution under physiological conditions at 6 h, respectively.

Interplay between intercalated oxygen superstructures and monolayer h -BN on Cu(100)

DOE PAGES

Ma, Chuanxu; Park, Jewook; Liu, Lei; ...

2016-08-18

The confinement effect of intercalated atoms in van der Waals heterostructures can lead to interesting interactions between the confined atoms or molecules and the overlaying two-dimensional (2D) materials. In this paper, we report the formation of ordered Cu(100) p(2×2) oxygen superstructures by oxygen intercalation under the monolayer hexagonal boron nitride (h-BN) on Cu after annealing. By using scanning tunneling microscopy and x-ray photoelectron spectroscopy, we identify the superstructure and reveal its roles in passivating the exposed Cu surfaces, decoupling h-BN and Cu, and disintegrating h-BN monolayers. The oxygen superstructure appears as a 2D pattern on the exposed Cu surface ormore » quasi-1D stripes of paired oxygen intercalated in the interface of h-BN and Cu predominantly oriented along the moiré modulations. The oxygen superstructure is shown to etch the overlaying h-BN monolayer in a thermal annealing process. After extended annealing, the h-BN monolayer disintegrates into nanoislands with zigzag edges. Finally, we discuss the implications of these findings on the stability and oxidation resistance of h-BN and relate them to challenges in process integration and 2D heterostructures.« less

Enhancement of the thrombolytic efficacy of prourokinase by lys-plasminogen in a dog model of arterial thrombosis.

PubMed

Badylak, S F; Voytik, S L; Henkin, J; Burke, S E; Sasahara, A A; Simmons, A

1991-05-01

Current findings suggest that the efficacy of thrombolytic therapy may be limited by the availability of active forms of plasminogen at the thrombus site. The purpose of this study was to determine if the systemic administration of 0.5 mg kg-1 glu-plasminogen (glu-plg) or 0.5 mg kg-1 lys-plasminogen (lys-plg) could safely increase the efficacy of a single intravenous bolus injection of 50,000 U kg-1 prourokinase (proUK) in a dog model of arterial thrombosis. Thrombolysis was measured by monitoring the continuous decrement of 125I-gamma emissions from a radiolabeled thrombus. Reflow was evaluated by direct visual examination. Forty dogs (mean wt 10.3 +/- 2 kg) were randomly sorted into 4 groups of 10 each. The dogs in each group were given either saline plus saline, saline plus proUK, glu-plg plus proUK, or lys-plg plus proUK 60 minutes after formation of an occlusive arterial thrombus. Ninety minutes after drug administration the dogs receiving saline plus proUK, glu-plg plus proUK, and the lys-plg plus proUK showed greater thrombolysis (41%, 43%, and 66%, respectively) than the control (saline plus saline) group (15%, P less than 0.01). The lys-plg plus proUK treatment caused greater lysis than the saline plus proUK or the glu-plg plus proUK treatment (P less than 0.05). All of the dogs (10/10) receiving lys-plg plus proUK had patent vessels at the end of the 90 minute monitoring period, whereas only 4/10 and 5/10 vessels were patent in the saline plus proUK and glu-plg plus proUK groups, respectively. None of the dogs in the saline plus saline group had patent vessels. No significant changes were observed in the various coagulation parameters tested for any of the 4 treatment groups. The results show that lys-plg can safely increase the thrombolytic efficacy of proUK.

BnNHL18A shows a localization change by stress-inducing chemical treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Suk-Bae; Ham, Byung-Kook; Park, Jeong Mee

2006-01-06

The two genes, named BnNHL18A and BnNHL18B, showing sequence homology with Arabidopsis NDR1/HIN1-like (NHL) genes, were isolated from cDNA library prepared with oilseed rape (Brassica napus) seedlings treated with NaCl. The transcript level of BnNHL18A was increased by sodium chloride, ethephon, hydrogen peroxide, methyl jasmonate, or salicylic acid treatment. The coding regions of BnNHL18A and BnNHL18B contain a sarcolipin (SLN)-like sequence. Analysis of the localization of smGFP fusion proteins showed that BnNHL18A is mainly localized to endoplasmic reticulum (ER). This result suggests that the SLN-like sequence plays a role in retaining proteins in ER membrane in plants. In response tomore » NaCl, hydrogen peroxide, ethephon, and salicylic acid treatments, the protein localization of BnNHL18A was changed. Our findings suggest a common function of BnNHL18A in biotic and abiotic stresses, and demonstrate the presence of the shared mechanism of protein translocalization between the responses to plant pathogen and to osmotic stress.« less

pSuc-Lys: Predict lysine succinylation sites in proteins with PseAAC and ensemble random forest approach.

PubMed

Jia, Jianhua; Liu, Zi; Xiao, Xuan; Liu, Bingxiang; Chou, Kuo-Chen

2016-04-07

Being one type of post-translational modifications (PTMs), protein lysine succinylation is important in regulating varieties of biological processes. It is also involved with some diseases, however. Consequently, from the angles of both basic research and drug development, we are facing a challenging problem: for an uncharacterized protein sequence having many Lys residues therein, which ones can be succinylated, and which ones cannot? To address this problem, we have developed a predictor called pSuc-Lys through (1) incorporating the sequence-coupled information into the general pseudo amino acid composition, (2) balancing out skewed training dataset by random sampling, and (3) constructing an ensemble predictor by fusing a series of individual random forest classifiers. Rigorous cross-validations indicated that it remarkably outperformed the existing methods. A user-friendly web-server for pSuc-Lys has been established at http://www.jci-bioinfo.cn/pSuc-Lys, by which users can easily obtain their desired results without the need to go through the complicated mathematical equations involved. It has not escaped our notice that the formulation and approach presented here can also be used to analyze many other problems in computational proteomics. Copyright © 2016 Elsevier Ltd. All rights reserved.

FGFR3-related condition: a skeletal dysplasia with similarities to thanatophoric dysplasia and SADDAN due to Lys650Met.

PubMed

Farmakis, Shannon G; Shinawi, Marwan; Miller-Thomas, Michelle; Radmanesh, Alireza; Herman, Thomas E

2015-03-01

Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene account for six related skeletal dysplasia conditions: achondroplasia, hypochondroplasia, thanatophoric dysplasia types 1 and 2, SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans), and platyspondylic lethal skeletal dysplasia, San Diego type. This group of disorders has very characteristic clinical and radiologic features, which distinguish them from other skeletal dysplasias. They display a spectrum of severity in the skeletal findings, ranging from relatively mild hypochondroplasia to lethal thanatophoric dysplasia. We report a patient who has the missense FGFR3 mutation, Lys650Met, previously reported in association only with SADDAN, who exhibits some findings similar to both thanatophoric dysplasia (types 1 and 2) in addition to those findings characteristic of SADDAN.

Sensitivity of BN nano-cages to caffeine and nicotine molecules

NASA Astrophysics Data System (ADS)

Soltani, Alireza; Baei, Mohammad T.; Tazikeh Lemeski, E.; Shahini, Malihe

2014-12-01

Adsorption of caffeine and nicotine molecules over B12N12 and B16N16 nano-cages were investigated by using first-principles calculations to define whether BN nano-cages are applicable for filtering or sensing caffeine and nicotine molecules. The chemisorption energy of nicotine molecule on BN nano-cages is very stronger than caffeine molecule. Upon the adsorption of caffeine and nicotine molecules, the electronic properties of the BN nano-cages can be significantly changed, being too much sensitized on the caffeine and nicotine adsorptions.

Context dependency of Set1/COMPASS-mediated histone H3 Lys4 trimethylation

PubMed Central

Thornton, Janet L.; Westfield, Gerwin H.; Takahashi, Yoh-hei; Cook, Malcolm; Gao, Xin; Woodfin, Ashley R.; Lee, Jung-Shin; Morgan, Marc A.; Jackson, Jessica; Smith, Edwin R.; Couture, Jean-Francois; Skiniotis, Georgios; Shilatifard, Ali

2014-01-01

The stimulation of trimethylation of histone H3 Lys4 (H3K4) by H2B monoubiquitination (H2Bub) has been widely studied, with multiple mechanisms having been proposed for this form of histone cross-talk. Cps35/Swd2 within COMPASS (complex of proteins associated with Set1) is considered to bridge these different processes. However, a truncated form of Set1 (762-Set1) is reported to function in H3K4 trimethylation (H3K4me3) without interacting with Cps35/Swd2, and such cross-talk is attributed to the n-SET domain of Set1 and its interaction with the Cps40/Spp1 subunit of COMPASS. Here, we used biochemical, structural, in vivo, and chromatin immunoprecipitation (ChIP) sequencing (ChIP-seq) approaches to demonstrate that Cps40/Spp1 and the n-SET domain of Set1 are required for the stability of Set1 and not the cross-talk. Furthermore, the apparent wild-type levels of H3K4me3 in the 762-Set1 strain are due to the rogue methylase activity of this mutant, resulting in the mislocalization of H3K4me3 from the promoter-proximal regions to the gene bodies and intergenic regions. We also performed detailed screens and identified yeast strains lacking H2Bub but containing intact H2Bub enzymes that have normal levels of H3K4me3, suggesting that monoubiquitination may not directly stimulate COMPASS but rather works in the context of the PAF and Rad6/Bre1 complexes. Our study demonstrates that the monoubiquitination machinery and Cps35/Swd2 function to focus COMPASS's H3K4me3 activity at promoter-proximal regions in a context-dependent manner. PMID:24402317

Phase stability limit of c-BN under hydrostatic and non-hydrostatic pressure conditions

NASA Astrophysics Data System (ADS)

Xiao, Jianwei; Du, Jinglian; Wen, Bin; Melnik, Roderick; Kawazoe, Yoshiyuki; Zhang, Xiangyi

2014-04-01

Phase stability limit of cubic boron nitride (c-BN) has been investigated by the crystal structure search technique. It indicated that this limit is ˜1000 GPa at hydrostatic pressure condition. Above this pressure, c-BN turns into a metastable phase with respect to rocksalt type boron nitride (rs-BN). However, rs-BN cannot be retained at 0 GPa owing to its instability at pressure below 250 GPa. For non-hydrostatic pressure conditions, the phase stability limit of c-BN is substantially lower than that under hydrostatic pressure conditions and it is also dramatically different for other pressure mode.

Phase stability limit of c-BN under hydrostatic and non-hydrostatic pressure conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, Jianwei; Du, Jinglian; Wen, Bin, E-mail: wenbin@ysu.edu.cn

2014-04-28

Phase stability limit of cubic boron nitride (c-BN) has been investigated by the crystal structure search technique. It indicated that this limit is ∼1000 GPa at hydrostatic pressure condition. Above this pressure, c-BN turns into a metastable phase with respect to rocksalt type boron nitride (rs-BN). However, rs-BN cannot be retained at 0 GPa owing to its instability at pressure below 250 GPa. For non-hydrostatic pressure conditions, the phase stability limit of c-BN is substantially lower than that under hydrostatic pressure conditions and it is also dramatically different for other pressure mode.

Electrical and Thermal Transport in Coplanar Polycrystalline Graphene-hBN Heterostructures.

PubMed

Barrios-Vargas, José Eduardo; Mortazavi, Bohayra; Cummings, Aron W; Martinez-Gordillo, Rafael; Pruneda, Miguel; Colombo, Luciano; Rabczuk, Timon; Roche, Stephan

2017-03-08

We present a theoretical study of electronic and thermal transport in polycrystalline heterostructures combining graphene (G) and hexagonal boron nitride (hBN) grains of varying size and distribution. By increasing the hBN grain density from a few percent to 100%, the system evolves from a good conductor to an insulator, with the mobility dropping by orders of magnitude and the sheet resistance reaching the MΩ regime. The Seebeck coefficient is suppressed above 40% mixing, while the thermal conductivity of polycrystalline hBN is found to be on the order of 30-120 Wm -1 K -1 . These results, agreeing with available experimental data, provide guidelines for tuning G-hBN properties in the context of two-dimensional materials engineering. In particular, while we proved that both electrical and thermal properties are largely affected by morphological features (e.g., by the grain size and composition), we find in all cases that nanometer-sized polycrystalline G-hBN heterostructures are not good thermoelectric materials.

Fungal effector Ecp6 outcompetes host immune receptor for chitin binding through intrachain LysM dimerization

PubMed Central

Kombrink, Anja; Hansen, Guido; Valkenburg, Dirk-Jan

2013-01-01

While host immune receptors detect pathogen-associated molecular patterns to activate immunity, pathogens attempt to deregulate host immunity through secreted effectors. Fungi employ LysM effectors to prevent recognition of cell wall-derived chitin by host immune receptors, although the mechanism to compete for chitin binding remained unclear. Structural analysis of the LysM effector Ecp6 of the fungal tomato pathogen Cladosporium fulvum reveals a novel mechanism for chitin binding, mediated by intrachain LysM dimerization, leading to a chitin-binding groove that is deeply buried in the effector protein. This composite binding site involves two of the three LysMs of Ecp6 and mediates chitin binding with ultra-high (pM) affinity. Intriguingly, the remaining singular LysM domain of Ecp6 binds chitin with low micromolar affinity but can nevertheless still perturb chitin-triggered immunity. Conceivably, the perturbation by this LysM domain is not established through chitin sequestration but possibly through interference with the host immune receptor complex. DOI: http://dx.doi.org/10.7554/eLife.00790.001 PMID:23840930

Potent μ-Opioid Receptor Agonists from Cyclic Peptides Tyr-c[D-Lys-Xxx-Tyr-Gly]: Synthesis, Biological, and Structural Evaluation.

PubMed

Li, Yangmei; Cazares, Margret; Wu, Jinhua; Houghten, Richard A; Toll, Laurence; Dooley, Colette

2016-02-11

To optimize the structure of a μ-opioid receptor ligand, analogs H-Tyr-c[D-Lys-Xxx-Tyr-Gly] were synthesized and their biological activity was tested. The analog containing a Phe(3) was identified as not only exhibiting binding affinity 14-fold higher than the original hit but also producing agonist activity 3-fold more potent than morphine. NMR study suggested that a trans conformation at D-Lys(2)-Xxx(3) is crucial for these cyclic peptides to maintain high affinity, selectivity, and functional activity toward the μ-opioid receptor.

Rapid Changes in the Structure of the BN Object

NASA Technical Reports Server (NTRS)

Danchi, William C.; Gezari, D. Y.; Greenhill, L. J.; Najita, J.; Monnier, J. D.; Tuthill, P. G.; Wishnow, E. H.; Townes, C. H.; Fisher, Richard R. (Technical Monitor)

2001-01-01

The BN/KL region in Orion is the archetypal region of high-mass star formation, radiating approx. 10(sup)5 Lsun and displaying promininent bulk outflows. In particular, there is no certain identification of the sources responsible for the high luminosity and outflows, and is the origin of a major explosive event (Shultz et al. 1999, ApJ, 511, 282). Using 18.7 and 12.5 micron data from observations in December 1999 and October 2000 made at the Keck I telescope, we discovered that the BN Object has a companion previously seen only at radio wavelengths (Menten & Reid 1995, ApJ, 445, L157). We call this companion B2 and it is about 1.5 arcsec West of the bright component. We also see changes in the shape of BN and the emission of "blobs" or "bullets" of material. While B2 remains unchanged and in the same place between the two epochs, there is an additional structure in BN to the South-South-East and the North-East, as well as a finger of material pointing North from B2 itself. Such a change has not been seen before in the infrared. We have looked very carefully at these images, calibrator images taken within a few minutes of the source images, as well as our previous images and cannot find any technical faults with the data. We explore the implications of these results, in particular, can these features be connected with previously observed "bullets" or "fingers" (see Allen & Burton 1993, for example), making BN a source for the bullets, implying they are not from IRc2 as previously thought? Or could they be produced by an interaction between material from BN and other sources such as IRc2?

An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, Jaslyn E. M. M.; Midtgaard, Søren Roi; Gysel, Kira

The crystal and solution structures of the T. thermophilus NlpC/P60 d, l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan. LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of themore » Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.« less

Electronic structure properties of deep defects in hBN

NASA Astrophysics Data System (ADS)

Dev, Pratibha; Prdm Collaboration

In recent years, the search for room-temperature solid-state qubit (quantum bit) candidates has revived interest in the study of deep-defect centers in semiconductors. The charged NV-center in diamond is the best known amongst these defects. However, as a host material, diamond poses several challenges and so, increasingly, there is an interest in exploring deep defects in alternative semiconductors such as hBN. The layered structure of hBN makes it a scalable platform for quantum applications, as there is a greater potential for controlling the location of the deep defect in the 2D-matrix through careful experiments. Using density functional theory-based methods, we have studied the electronic and structural properties of several deep defects in hBN. Native defects within hBN layers are shown to have high spin ground states that should survive even at room temperature, making them interesting solid-state qubit candidates in a 2D matrix. Partnership for Reduced Dimensional Material (PRDM) is part of the NSF sponsored Partnerships for Research and Education in Materials (PREM).

Exploring the Potential of (99m)Tc(CO)3-Labeled Triazolyl Peptides for Tumor Diagnosis.

PubMed

Gaonkar, Raghuvir H; Ganguly, Soumya; Baishya, Rinku; Dewanjee, Saikat; Sinha, Samarendu; Gupta, Amit; Ganguly, Shantanu; Debnath, Mita C

2016-04-01

In recent years the authors have reported on (99m)Tc(CO)3-labeled peptides that serve as carriers for biomolecules or radiopharmaceuticals to the tumors. In continuation of that work they report the synthesis of a pentapeptide (Met-Phe-Phe-Gly-His; pep-1), a hexapeptide (Met-Phe-Phe-Asp-Gly-His; pep-2), and a tetrapeptide (Asp-Gly-Arg-His; pep-3) and the attachment of 3-amino-1,2,4-triazole to the β carboxylic function of the aspartic acid unit of pep-2 and pep-3. The pharmacophores were radiolabeled in high yields with [(99m)Tc(CO)3(H2O)3](+) metal aqua ion, characterized for their stability in serum and saline, as well as in His solution, and found to be substantially stable. B16F10 cell line binding studies showed favorable uptake and internalization. In vivo behavior of the radiolabeled triazolyl peptides was assessed in mice bearing induced tumor. The (99m)Tc(CO)3-triazolyl pep-3 demonstrated rapid urinary clearance and comparatively better tumor uptake. Imaging studies showed visualization of the tumor using (99m)Tc(CO)3-triazolyl pep-3, but due to high abdominal background, low delineation occurred. Based on the results further experiments will be carried out for targeting tumor with triazolyl peptides.

Characterization of TCP-1 probes for molecular imaging of colon cancer.

PubMed

Liu, Zhonglin; Gray, Brian D; Barber, Christy; Bernas, Michael; Cai, Minying; Furenlid, Lars R; Rouse, Andrew; Patel, Charmi; Banerjee, Bhaskar; Liang, Rongguang; Gmitro, Arthur F; Witte, Marlys H; Pak, Koon Y; Woolfenden, James M

2016-10-10

Molecular probes capable of detecting colorectal cancer (CRC) are needed for early CRC diagnosis. The objective of this study was to characterize c[CTPSPFSHC]OH (TCP-1), a small peptide derived from phage display selection, for targeting human CRC xenografts using technetium-99m ((99m)Tc)-labeled TCP-1 and fluorescent cyanine-7 (Cy7)-labeled form of the peptide (Cy7-TCP-1). (99m)Tc-TCP-1 was generated by modifying TCP-1 with succinimidyl-6-hydrazino-nicotinamide (S-HYNIC) followed by radiolabeling. In vitro saturation binding experiments were performed for (99m)Tc-TCP-1 in human HCT116 colon cancer cells. SCID mice with human HCT116 cancer xenografts were imaged with (99m)Tc-TCP-1 or control peptide using a small-animal SPECT imager: Group I (n=5) received no blockade; Group II (n=5) received a blocking dose of non-radiolabeled TCP-1. Group III (n=5) were imaged with (99m)Tc-labeled control peptide (inactive peptide). SCID mice with human PC3 prostate cancer xenografts (Group IV, n=5) were also imaged with (99m)Tc-TCP-1. Eight additional SCID mice bearing HCT116 xenografts in dorsal skinfold window chambers (DSWC) were imaged by direct positron imaging of (18)F-fluorodeoxyglucose ((18)F-FDG) and fluorescence microscopy of Cy7-TCP-1. In vitro(99m)Tc-HYNIC-TCP-1 binding assays on HCT 116 cells indicated a mean Kd of 3.04±0.52nM. In cancer xenografts, (99m)Tc-TCP-1 radioactivity (%ID/g) was 1.01±0.15 in the absence of blockade and was reduced to 0.26±0.04 (P<0.01) with blockade. No radioactive uptake was observed in the PC3 tumors with (99m)Tc-TCP-1 or HCT116 tumors with inactive peptide. Cy7-TCP-1 activity localized not only in metabolically active tumors, as defined by (18)F-FDG imaging, but also in peritumoral microvasculature. In conclusion, TCP-1 probes may have a distinct targeting mechanism with high selectivity for CRC and tumor-associated vasculature. Molecular imaging with TCP-1 probes appears promising to detect malignant colorectal lesions. Copyright �

SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections.

PubMed

Monteiro, Paulo Henrique Silva; de Souza, Thiago Ferreira; Moretti, Maria Luiza; Resende, Mariangela Ribeiro; Mengatti, Jair; de Lima, Mariana da Cunha Lopes; Santos, Allan Oliveira; Ramos, Celso Darío

2017-01-01

To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 ( 67 Ga) citrate scintigraphy. We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99m Tc-EDDA-HYNIC-TOC, and 21 after injection of 111 In-DTPA-octreotide. All patients also underwent 67 Ga citrate imaging, except for one patient who died before the 67 Ga was available. In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67 Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67 Ga uptake in 11 of the 20 patients with positive images and similar to 67 Ga uptake in the other 9 patients. The only patient who did not undergo 67 Ga scintigraphy underwent 99m Tc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. SPECT/CT with 99m Tc-EDDA-HYNIC-TOC or 111 In-DTPA-octreotide seems to be a good alternative to 67 Ga citrate imaging for the evaluation of patients with systemic granulomatous disease.

Recognition of Lys48-Linked Di-ubiquitin and Deubiquitinating Activities of the SARS Coronavirus Papain-like Protease.

PubMed

Békés, Miklós; van der Heden van Noort, Gerbrand J; Ekkebus, Reggy; Ovaa, Huib; Huang, Tony T; Lima, Christopher D

2016-05-19

Deubiquitinating enzymes (DUBs) recognize and cleave linkage-specific polyubiquitin (polyUb) chains, but mechanisms underlying specificity remain elusive in many cases. The severe acute respiratory syndrome (SARS) coronavirus papain-like protease (PLpro) is a DUB that cleaves ISG15, a two-domain Ub-like protein, and Lys48-linked polyUb chains, releasing diUb(Lys48) products. To elucidate this specificity, we report the 2.85 Å crystal structure of SARS PLpro bound to a diUb(Lys48) activity-based probe. SARS PLpro binds diUb(Lys48) in an extended conformation via two contact sites, S1 and S2, which are proximal and distal to the active site, respectively. We show that specificity for polyUb(Lys48) chains is predicated on contacts in the S2 site and enhanced by an S1-S1' preference for a Lys48 linkage across the active site. In contrast, ISG15 specificity is dominated by contacts in the S1 site. Determinants revealed for polyUb(Lys48) specificity should prove useful in understanding PLpro deubiquitinating activities in coronavirus infections. Copyright © 2016 Elsevier Inc. All rights reserved.

Macrocyclic triamine derived glucose analogues for 99m Tc(CO)3 labeling: synthesis and biological evaluation as potential tumor-imaging agents.

PubMed

Liu, Teli; Gan, Qianqian; Zhang, Junbo

2017-02-01

[ 99m Tc(CO) 3 (H 2 O) 3 ] + has attracted great attention among 99m Tc-labeling techniques, due to its ease of preparation, readily substituted water molecules of the precursor fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + by a variety of functional groups, small size and inertness. Bifunctional chelator based on a macrocyclic polyamine framework shows easy complexation with [ 99m Tc(CO) 3 (H 2 O) 3 ] + to produce stable complex. In this study, two novel 1, 5, 9-triazacyclododecane derivatives containing a glucose group (6 and 7) were successfully synthesized by reacting different glucose-azides with alkyne-[12]aneN 3 via the so-called click chemistry and radiolabeled with [ 99m Tc(CO) 3 (H 2 O) 3 ] + to form 99m Tc(CO) 3 -6 (C-1-substituted complex) and 99m Tc(CO) 3 -7 (C-2-substituted complex) in high yields. The complexes were stable in vitro over 6 h when incubated in saline at room temperature and in mouse serum at 37 °C. The partition coefficient results showed that they were hydrophilic. The biodistribution studies in Kunming mice bearing S 180 tumor showed both complexes showed accumulation in the tumor. Between them, 99m Tc(CO) 3 -7 had the advantages of much higher tumor uptake and tumor/muscle ratio. Compared with other reported 99m Tc-radiolabeled glucose derivatives, 99m Tc(CO) 3 -7 also showed a higher tumor uptake and tumor/muscle ratio, suggesting it would be a potential candidate for further development as a tumor-imaging agent. © 2017 John Wiley & Sons A/S.

OAT3-mediated extrusion of the 99mTc-ECD metabolite in the mouse brain

PubMed Central

Kikuchi, Tatsuya; Okamura, Toshimitsu; Wakizaka, Hidekatsu; Okada, Maki; Odaka, Kenichi; Yui, Joji; Tsuji, Atsushi B; Fukumura, Toshimitsu; Zhang, Ming-Rong

2014-01-01

After administration of the 99mTc complex with N,N'-1,2-ethylenediylbis-L-cysteine diethyl ester (99mTc-ECD), a brain perfusion imaging agent, the radioactive metabolite is trapped in primate brain, but not in mouse and rat. Here, we investigate the involvement of metabolite extrusion by organic anion transporter 3 (OAT3), which is highly expressed at the blood–brain barrier in mice, in this species difference. The efflux rate of radioactivity in the cerebrum of Oat3−/− mice at later phase was 20% of that of control mice. Thus, organic anion transporters in mouse brain would be involved in the low brain retention of radioactivity after 99mTc-ECD administration. PMID:24496177

Comparison of trapped charges and hysteresis behavior in hBN encapsulated single MoS2 flake based field effect transistors on SiO2 and hBN substrates.

PubMed

Lee, Changhee; Rathi, Servin; Khan, Muhammad Atif; Lim, Dongsuk; Kim, Yunseob; Yun, Sun Jin; Youn, Doo-Hyeb; Watanabe, Kenji; Taniguchi, Takashi; Kim, Gil-Ho

2018-08-17

Molybdenum disulfide (MoS 2 ) based field effect transistors (FETs) are of considerable interest in electronic and opto-electronic applications but often have large hysteresis and threshold voltage instabilities. In this study, by using advanced transfer techniques, hexagonal boron nitride (hBN) encapsulated FETs based on a single, homogeneous and atomic-thin MoS 2 flake are fabricated on hBN and SiO 2 substrates. This allows for a better and a precise comparison between the charge traps at the semiconductor-dielectric interfaces at MoS 2 -SiO 2 and hBN interfaces. The impact of ambient environment and entities on hysteresis is minimized by encapsulating the active MoS 2 layer with a single hBN on both the devices. The device to device variations induced by different MoS 2 layer is also eliminated by employing a single MoS 2 layer for fabricating both devices. After eliminating these additional factors which induce variation in the device characteristics, it is found from the measurements that the trapped charge density is reduced to 1.9 × 10 11 cm -2 on hBN substrate as compared to 1.1 × 10 12 cm -2 on SiO 2 substrate. Further, reduced hysteresis and stable threshold voltage are observed on hBN substrate and their dependence on gate sweep rate, sweep range, and gate stress is also studied. This precise comparison between encapsulated devices on SiO 2 and hBN substrates further demonstrate the requirement of hBN substrate and encapsulation for improved and stable performance of MoS 2 FETs.

[(99m)Tc(CO)(3)]-radiolabeled bevacizumab: in vitro and in vivo evaluation in a melanoma model.

PubMed

Camacho, Ximena; García, María Fernanda; Calzada, Victoria; Fernández, Marcelo; Chabalgoity, Jose A; Moreno, Maria; Barbosa de Aguiar, Rodrigo; Alonso, Omar; Gambini, Juan Pablo; Chammas, Roger; Cabral, Pablo

2013-01-01

Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several tumor types, including melanoma. Bevacizumab, a monoclonal antibody against VEGF, could be used as an imaging tool in preclinical studies. To radiolabel bevacizumab with [(99m)Tc(CO)3(OH2)3](+) and evaluate it in vivo and in vitro for melanoma imaging properties. Bevacizumab was radiolabeled with [(99m)Tc(CO)3(OH2)3](+) ion in saline. The radiochemical stability of the labeled antibody was assessed. The biodistribution and scintigraphy imaging of the radiolabeled antibody were evaluated in normal C57BL/6J mice and in C57BL/6J mice bearing murine B16F1 melanoma tumors. Immunoreactivity of bevacizumab to murine tumors was determined from direct immunofluorescence and immunoblotting assays. We demonstrate that (99m)Tc(CO)3-bevacizumab was stable. In vivo biodistribution studies revealed that tumor uptake of (99m)Tc(CO)3-bevacizumab was 2.64 and 2.51 %ID/g at 4 and 24 h postinjection. Scintigraphy image studies showed tumor selective uptake of (99m)Tc(CO)3-bevacizumab in the tumor-bearing mice. This affinity was confirmed by immunoassays performed on B16F10 tumor samples. (99m)Tc(CO)3-bevacizumab could be used as an approach for tumor nuclear imaging in preclinical studies. This should be useful to provide insights into the angiogenic stimulus before and after chemotherapy, which might help improve current antitumor therapy. Copyright © 2013 S. Karger AG, Basel.

Structural analysis of graphene and h-BN: A molecular dynamics approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, Siby; Ajith, K. M., E-mail: ajith@nitk.ac.in; Valsakumar, M. C.

2016-05-06

Classical molecular dynamics simulation is employed to analyze pair correlations in graphene and h-BN at various temperatures to explore the integrity of their respective structures. As the temperature increases, the height fluctuations in the out-of-plane direction of both graphene and h-BN are found to increase. The positional spread of atoms also increases with temperature. Thus the amplitude of the peak positions in the radial distribution function (RDF) decreases with temperature. It is found that FWHM of peaks in the RDF of h-BN is smaller as compared to those of graphene which implies that the structure of h-BN is more robustmore » as compared to that of graphene with respect to their respective empirical potential.« less

High Temperature Si-doped BN Interphases for Woven SiC/SiC Composites

NASA Technical Reports Server (NTRS)

Morscher, Gregory N.; Hurwitz, Frances; Yun, Hee Mann; Gray, Hugh R. (Technical Monitor)

2002-01-01

The hydrolytic stability of high-temperature deposited Si-doped BN has been shown in the past to be superior in comparison to "pure" BN processed at similar or even higher temperatures. This type of material would be very desirable as a SiC/SiC composite interphase that is formed by chemical infiltration into multi-ply woven preform. However, due to rapid deposition on the preform outer surface at the high processing temperature, this has proven very difficult. To overcome this issue, single plies of woven fabric were infiltrated with Si-doped BN. Three composite panels of different SiC fiber types were fabricated with Si-doped BN interphases including Sylramic, Hi-Nicalon Type S and Sylramic-iBN fiber-types. The latter fiber-type possesses a thin in-situ grown BN layer on the fiber surface. High Si contents (approx. 7 to 10 a/o) and low oxygen contents (less than 1 a/o) were achieved. All three composite systems demonstrated reasonable debonding and sliding properties. The coated Sylramic fabric and composites were weak due to fiber degradation apparently caused during interphase processing by the formation of TiN crystals on the fiber surface. The Hi-Nicalon Type S composites with Si-doped BN interphase were only slightly weaker than Hi-Nicalon Type S composites with conventional BN when the strength on the load-bearing fibers at failure was compared. On the other hand, the Sylramic-iBN fabric and composites with Si-doped BN showed excellent composite and intermediate temperature stress-rupture properties. Most impressive was the lack of any significant interphase oxidation on the fracture surface of stress-ruptured specimens tested well above matrix cracking at 815C.

Tumor bombesin analog loaded long-circulating and pH-sensitive liposomes as tool for tumor identification.

PubMed

de Barros, André Luís Branco; Mota, Luciene das Graças; Soares, Daniel Crístian Ferreira; Coelho, Marina Melo Antunes; Oliveira, Mônica Cristina; Cardoso, Valbert Nascimento

2011-12-15

Long-circulating and pH-sensitive liposomes trapping (99m)Tc-HYNIC-βAla-bombesin((7-14)) (aSpHL-(99m)Tc-BBN((7-14))) were successfully prepared. Biodistribution studies and scintigraphic images were performed in Ehrlich tumor-bearing Swiss mice. This system showed high accumulation in tumor tissue with high tumor-to-muscle ratio. Therefore, aSpHL-(99m)Tc-BBN((7-14)) could be considered as a potential agent for tumor diagnosis. Published by Elsevier Ltd.

Antitumor effects of cationic synthetic peptides derived from Lys49 phospholipase A2 homologues of snake venoms.

PubMed

Araya, Cindy; Lomonte, Bruno

2007-03-01

The effects of two cationic synthetic peptides, derived from the C-terminal region of Lys49 phospholipase A2 homologues from snake venoms, upon various murine tumor cell lines (B16 melanoma, EMT6 mammary carcinoma, S-180 sarcoma, P3X myeloma, tEnd endothelial cells) were evaluated. The peptides are 13-mers derived from Agkistrodon piscivorus piscivorus Lys49 PLA2 (p-AppK: KKYKAYFKLKCKK) and Bothrops asper Lys49 myotoxin II (pEM-2[D]: KKWRWWLKALAKK), respectively, in the latter case with slight modifications and with all-D amino acids. All tumor cells tested were susceptible to the lytic action of the peptides. The susceptibility of tumor cell lines was not higher than that of C2C12 skeletal muscle myoblasts, utilized as a non-transformed cell line control. However, in a murine model of subcutaneous solid tumor growth of EMT6 mammary carcinoma, the intraperitoneal administration of pEM-2[D] caused a tumor mass reduction of 36% (p<0.05), which was of similar magnitude to that achieved by the administration of paclitaxel, an antitumor drug in clinical use. Thus, the C-terminal peptides of Lys49 phospholipase A2 homologues present antitumor effects that might be of interest in developing therapeutic strategies against cancer.

Dielectric Properties of Boron Nitride-Ethylene Glycol (BN-EG) Nanofluids

NASA Astrophysics Data System (ADS)

Fal, Jacek; Cholewa, Marian; Gizowska, Magdalena; Witek, Adam; ŻyŁa, GaweŁ

2017-02-01

This paper presents the results of experimental investigation of the dielectric properties of ethylene glycol (EG) with various load of boron nitride (BN) nanoparticles. The nanofuids were prepared by using a two-step method on the basis of commercially available BN nanoparticles. The measurements were carried out using the Concept 80 System (NOVOCONTROL Technologies GmbH & Co. KG, Montabaur, Germany) in a frequency range from 10 Hz to 10 MHz and temperatures from 278.15 K to 328.15 K. The frequency-dependent real (ɛ ^' }) and imaginary (ɛ ^' ' }) parts of the complex permittivity (ɛ ^*) and the alternating current (AC) conductivity are presented. Also, the effect of temperature and mass concentrations on the dielectric properties of BN-EG nanofluids are demonstrated. The results show that the most significant increase can be achieved for 20 wt.% of BN nanoparticles at 283.15 K and 288.15 K, that is eleven times larger than in the case of pure EG.

Thermally activated hysteresis in high quality graphene/h-BN devices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cadore, A. R., E-mail: alissoncadore@gmail.com, E-mail: lccampos@fisica.ufmg.br; Mania, E.; Lacerda, R. G.

2016-06-06

We report on gate hysteresis of resistance in high quality graphene/hexagonal boron nitride (h-BN) devices. We observe a thermally activated hysteretic behavior in resistance as a function of the applied gate voltage at temperatures above 375 K. In order to investigate the origin of the hysteretic phenomenon, we compare graphene/h-BN heterostructure devices with SiO{sub 2}/Si back gate electrodes to devices with graphite back gate electrodes. The gate hysteretic behavior of the resistance is present only in devices with an h-BN/SiO{sub 2} interface and is dependent on the orientation of the applied gate electric field and sweep rate. We describe a phenomenologicalmore » model which captures all of our findings based on charges trapped at the h-BN/SiO{sub 2} interface. Such hysteretic behavior in graphene resistance must be considered in high temperature applications for graphene devices and may open new routes for applications in digital electronics and memory devices.« less

Targeted disruption of TC-PTP in the proliferative compartment augments STAT3 and AKT signaling and skin tumor development.

PubMed

Lee, Hyunseung; Kim, Mihwa; Baek, Minwoo; Morales, Liza D; Jang, Ik-Soon; Slaga, Thomas J; DiGiovanni, John; Kim, Dae Joon

2017-03-21

Tyrosine phosphorylation is a vital mechanism that contributes to skin carcinogenesis. It is regulated by the counter-activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Here, we report the critical role of T-cell protein tyrosine phosphatase (TC-PTP), encoded by Ptpn2, in chemically-induced skin carcinogenesis via the negative regulation of STAT3 and AKT signaling. Using epidermal specific TC-PTP knockout (K14Cre.Ptpn2 fl/fl ) mice, we demonstrate loss of TC-PTP led to a desensitization to tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA)-induced apoptosis both in vivo epidermis and in vitro keratinocytes. TC-PTP deficiency also resulted in a significant increase in epidermal thickness and hyperproliferation following exposure to the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Western blot analysis showed that both phosphorylated STAT3 and phosphorylated AKT expressions were significantly increased in epidermis of TC-PTP-deficient mice compared to control mice following TPA treatment. Inhibition of STAT3 or AKT reversed the effects of TC-PTP deficiency on apoptosis and proliferation. Finally, TC-PTP knockout mice showed a shortened latency of tumorigenesis and significantly increased numbers of tumors during two-stage skin carcinogenesis. Our findings reveal that TC-PTP has potential as a novel target for the prevention of skin cancer through its role in the regulation of STAT3 and AKT signaling.

Targeted disruption of TC-PTP in the proliferative compartment augments STAT3 and AKT signaling and skin tumor development

PubMed Central

Lee, Hyunseung; Kim, Mihwa; Baek, Minwoo; Morales, Liza D.; Jang, Ik-Soon; Slaga, Thomas J.; DiGiovanni, John; Kim, Dae Joon

2017-01-01

Tyrosine phosphorylation is a vital mechanism that contributes to skin carcinogenesis. It is regulated by the counter-activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Here, we report the critical role of T-cell protein tyrosine phosphatase (TC-PTP), encoded by Ptpn2, in chemically-induced skin carcinogenesis via the negative regulation of STAT3 and AKT signaling. Using epidermal specific TC-PTP knockout (K14Cre.Ptpn2fl/fl) mice, we demonstrate loss of TC-PTP led to a desensitization to tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA)-induced apoptosis both in vivo epidermis and in vitro keratinocytes. TC-PTP deficiency also resulted in a significant increase in epidermal thickness and hyperproliferation following exposure to the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Western blot analysis showed that both phosphorylated STAT3 and phosphorylated AKT expressions were significantly increased in epidermis of TC-PTP-deficient mice compared to control mice following TPA treatment. Inhibition of STAT3 or AKT reversed the effects of TC-PTP deficiency on apoptosis and proliferation. Finally, TC-PTP knockout mice showed a shortened latency of tumorigenesis and significantly increased numbers of tumors during two-stage skin carcinogenesis. Our findings reveal that TC-PTP has potential as a novel target for the prevention of skin cancer through its role in the regulation of STAT3 and AKT signaling. PMID:28322331

Vibration responses of h-BN sheet to charge doping and external strain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Wei; Yang, Yu; Zheng, Fawei

2013-12-07

Based on density functional theory and density functional perturbation theory calculations, we systematically investigate the vibration responses of h-BN sheet to charge doping and external strains. It is found that under hole doping, the phonon frequencies of the ZO and TO branches at different wave vector q shift linearly with different slopes. Under electron doping, although the phonon frequencies shift irregularly, the shifting values are different at different phonon wave vectors. Interestingly, we find that external strain can restrain the irregular vibration responses of h-BN sheet to electron doping. The critical factor is revealed to be the relative position ofmore » the nearly free electron and boron p{sub z} states of h-BN sheet. Under external strains, the vibration responses of h-BN sheet are also found to be highly dependent on the phonon branches. Different vibration modes at different q points are revealed to be responsible for the vibration responses of h-BN sheet to charge doping and external strain. Our results point out a new way to detect the doping or strain status of h-BN sheet by measuring the vibration frequencies at different wave vector.« less

2D Hexagonal Boron Nitride (2D-hBN) Explored for the Electrochemical Sensing of Dopamine.

PubMed

Khan, Aamar F; Brownson, Dale A C; Randviir, Edward P; Smith, Graham C; Banks, Craig E

2016-10-04

significant increase in the peak current of DA. The limit of detection (3σ) is found to correspond to 0.65 μM for DA in the presence of UA. However, it is not possible to deconvolute the simultaneous detection of DA and AA. The observed electrocatalytic effect at 2D-hBN has not previously been reported in the literature when supported upon carbon or any other electrode. We provide valuable insights into the modifier-substrate interactions of this material, essential for those designing, fabricating, and consequently performing electrochemical experiments utilizing 2D-hBN and related 2D materials.

Synthesis and preliminary evaluation of a new (99m)tc labeled substance p analogue as a potential tumor imaging agent.

PubMed

Mozaffari, Saeed; Erfani, Mostafa; Beiki, Davood; Johari Daha, Fariba; Kobarfard, Farzad; Balalaie, Saeed; Fallahi, Babak

2015-01-01

Neurokinin 1 receptors (NK1R) are overexpressed on several types of important human cancer cells. Substance P (SP) is the most specific endogenous ligand known for NK1Rs. Accordingly,a new SP analogue was synthesized and evaluated for detection of NK1R positive tumors.[6-hydrazinopyridine-3-carboxylic acid (HYNIC)-Tyr(8)-Met(O)(11)-SP] was synthesized and radiolabeled with (99m)Tc using ethylenediamine-N,N'-diacetic acid (EDDA)and Tricine as coligands. Common physicochemical properties of radioconjugate were studied and in-vitro cell line biological tests were accomplished to determine the receptor mediated characteristics. In-vivo biodistribution in normal and tumor bearingnude mice was also assessed. The cold peptide was prepared in high purity (>99%) and radiolabeled with (99m)Tc at high specific activities (84-112GBq/µmol) with an acceptable labeling yield (>95%). The radioconjugate was stable in-vitro in the presence of human serum and showed 44% protein binding to human serumalbumin. In-vitro cell line studies on U373MG cells showed an acceptable uptake up to 4.91 ± 0.22% with the ratio of 60.21 ± 1.19% for its specific fraction and increasing specific internalization during 4 h. Receptor binding assays on U373MG cells indicated a mean Kd of 2.46 ± 0.43 nM and Bmax of 128925 ± 8145 sites/cell. In-vivo investigations determined the specific tumor uptake in 3.36 percent of injected dose per gram (%ID/g) for U373MG cells and noticeable accumulations of activity in the intestines and lung. Predominant renal excretion pathway was demonstrated. Therefore, this new radiolabeled peptide could be a promising radiotracer for detection of NK1R positive primary or secondary tumors.

Synthesis and Preliminary Evaluation of a New 99mTc Labeled Substance P Analogue as a Potential Tumor Imaging Agent

PubMed Central

Mozaffari, Saeed; Erfani, Mostafa; Beiki, Davood; Johari Daha, Fariba; Kobarfard, Farzad; Balalaie, Saeed; Fallahi, Babak

2015-01-01

Neurokinin 1 receptors (NK1R) are overexpressed on several types of important human cancer cells. Substance P (SP) is the most specific endogenous ligand known for NK1Rs. Accordingly,a new SP analogue was synthesized and evaluated for detection of NK1R positive tumors.[6-hydrazinopyridine-3-carboxylic acid (HYNIC)-Tyr8-Met(O)11-SP] was synthesized and radiolabeled with 99mTc using ethylenediamine-N,N'-diacetic acid (EDDA)and Tricine as coligands. Common physicochemical properties of radioconjugate were studied and in-vitro cell line biological tests were accomplished to determine the receptor mediated characteristics. In-vivo biodistribution in normal and tumor bearingnude mice was also assessed. The cold peptide was prepared in high purity (>99%) and radiolabeled with 99mTc at high specific activities (84-112GBq/µmol) with an acceptable labeling yield (>95%). The radioconjugate was stable in-vitro in the presence of human serum and showed 44% protein binding to human serumalbumin. In-vitro cell line studies on U373MG cells showed an acceptable uptake up to 4.91 ± 0.22% with the ratio of 60.21 ± 1.19% for its specific fraction and increasing specific internalization during 4 h. Receptor binding assays on U373MG cells indicated a mean Kd of 2.46 ± 0.43 nM and Bmax of 128925 ± 8145 sites/cell. In-vivo investigations determined the specific tumor uptake in 3.36 percent of injected dose per gram (%ID/g) for U373MG cells and noticeable accumulations of activity in the intestines and lung. Predominant renal excretion pathway was demonstrated. Therefore, this new radiolabeled peptide could be a promising radiotracer for detection of NK1R positive primary or secondary tumors. PMID:25561916

Extended Tersoff potential for boron nitride: Energetics and elastic properties of pristine and defective h -BN

NASA Astrophysics Data System (ADS)

Los, J. H.; Kroes, J. M. H.; Albe, K.; Gordillo, R. M.; Katsnelson, M. I.; Fasolino, A.

2017-11-01

We present an extended Tersoff potential for boron nitride (BN-ExTeP) for application in large scale atomistic simulations. BN-ExTeP accurately describes the main low energy B, N, and BN structures and yields quantitatively correct trends in the bonding as a function of coordination. The proposed extension of the bond order, added to improve the dependence of bonding on the chemical environment, leads to an accurate description of point defects in hexagonal BN (h -BN) and cubic BN (c -BN). We have implemented this potential in the molecular dynamics LAMMPS code and used it to determine some basic properties of pristine 2D h -BN and the elastic properties of defective h -BN as a function of defect density at zero temperature. Our results show that there is a strong correlation between the size of the static corrugation induced by the defects and the weakening of the in-plane elastic moduli.

Graphene/h-BN/GaAs sandwich diode as solar cell and photodetector.

PubMed

Li, Xiaoqiang; Lin, Shisheng; Lin, Xing; Xu, Zhijuan; Wang, Peng; Zhang, Shengjiao; Zhong, Huikai; Xu, Wenli; Wu, Zhiqian; Fang, Wei

2016-01-11

In graphene/semiconductor heterojunction, the statistic charge transfer between graphene and semiconductor leads to decreased junction barrier height and limits the Fermi level tuning effect in graphene, which greatly affects the final performance of the device. In this work, we have designed a sandwich diode for solar cells and photodetectors through inserting 2D hexagonal boron nitride (h-BN) into graphene/GaAs heterostructure to suppress the static charge transfer. The barrier height of graphene/GaAs heterojunction can be increased from 0.88 eV to 1.02 eV by inserting h-BN. Based on the enhanced Fermi level tuning effect with interface h-BN, through adopting photo-induced doping into the device, power conversion efficiency (PCE) of 10.18% has been achieved for graphene/h-BN/GaAs compared with 8.63% of graphene/GaAs structure. The performance of graphene/h-BN/GaAs based photodetector is also improved with on/off ratio increased by one magnitude compared with graphene/GaAs structure.

Monitoring Tc dynamics in a bioreduced sediment: an investigation with gamma camera imaging of (99m)Tc-pertechnetate and (99m)Tc-DTPA.

PubMed

Vandehey, Nicholas T; O'Neil, James P; Slowey, Aaron J; Boutchko, Rostyslav; Druhan, Jennifer L; Moses, William W; Nico, Peter S

2012-11-20

We demonstrate the utility of nuclear medical imaging technologies and a readily available radiotracer, [(99m)Tc]TcO(4)(-), for the noninvasive monitoring of Fe(II) production in acetate-stimulated sediments from Old Rifle, CO, USA. Microcosms consisting of sediment in artificial groundwater media amended with acetate were probed by repeated injection of radiotracer over three weeks. Gamma camera imaging was used to noninvasively quantify the rate and extent of [(99m)Tc]TcO(4)(-) partitioning from solution to sediment. Aqueous Fe(II) and sediment-associated Fe(II) were also measured and correlated with the observed tracer behavior. For each injection of tracer, curves of (99m)Tc concentration in solution vs time were fitted to an analytic function that accounts for both the observed rate of sedimentation as well as the rate of (99m)Tc association with the sediment. The rate and extent of (99m)Tc association with the biostimulated sediment correlated well with the production of Fe(II), and a mechanism of [(99m)Tc]TcO(4)(-) reduction via reaction with surface-bound Fe(II) to form an immobile Tc(IV) species was inferred. After three weeks of bioreduction, a subset of microcosms was aerated in order to reoxidize the Fe(II) to Fe(III), which also destroyed the affinity of the [(99m)Tc]TcO(4)(-) for the sediments. However, within 3 days postoxidation, the rate of Tc(VII) reduction was faster than immediately before oxidation implying a rapid return to more extensive bioreduction. Furthermore, aeration soon after a tracer injection showed that sediment-bound Tc(IV) is rapidly resolubilized to Tc(VII). In contrast to the [(99m)Tc]TcO(4)(-), a second commercially available tracer, (99m)Tc-DTPA (diethylenetriaminepentaacetic acid), had minimal association with sediment in both controls and biostimulated sediments. These experiments show the promise of [(99m)Tc]TcO(4)(-) and (99m)Tc-DTPA as noninvasive imaging probes for a redox-sensitive radiotracer and a conservative flow

OTUB1 Co-opts Lys48-Linked Ubiquitin Recognition to Suppress E2 Enzyme Function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Juang, Yu-Chi; Landry, Marie-Claude; Sanches, Mario

2012-03-26

Ubiquitylation entails the concerted action of E1, E2, and E3 enzymes. We recently reported that OTUB1, a deubiquitylase, inhibits the DNA damage response independently of its isopeptidase activity. OTUB1 does so by blocking ubiquitin transfer by UBC13, the cognate E2 enzyme for RNF168. OTUB1 also inhibits E2s of the UBE2D and UBE2E families. Here we elucidate the structural mechanism by which OTUB1 binds E2s to inhibit ubiquitin transfer. OTUB1 recognizes ubiquitin-charged E2s through contacts with both donor ubiquitin and the E2 enzyme. Surprisingly, free ubiquitin associates with the canonical distal ubiquitin-binding site on OTUB1 to promote formation of the inhibitedmore » E2 complex. Lys48 of donor ubiquitin lies near the OTUB1 catalytic site and the C terminus of free ubiquitin, a configuration that mimics the products of Lys48-linked ubiquitin chain cleavage. OTUB1 therefore co-opts Lys48-linked ubiquitin chain recognition to suppress ubiquitin conjugation and the DNA damage response.« less

Identification of novel mammalian hosts and Brazilian biome geographic distribution of Trypanosoma cruzi TcIII and TcIV.

PubMed

Barros, Juliana Helena S; Xavier, Samanta Cristina C; Bilac, Daniele; Lima, Valdirene Santos; Dario, Maria Augusta; Jansen, Ana Maria

2017-08-01

Trypanosoma cruzi is a parasitic protozoan responsible for Chagas disease. Seven different Discrete Typing Units (DTUs) of T. cruzi are currently identified in nature: TcI-TcVI, and TcBat whose distribution patterns in nature, hosts/reservoirs and eco-epidemiological importance are still little known. Here, we present novel data on the geographic distribution and diversity of mammalian hosts and vectors of T. cruzi DTUs TcIII and TcIV. In this study, we analyzed 61 T. cruzi isolates obtained from 18 species of mammals (five orders) and two Hemiptera genera. Samples were collected from five Brazilian biomes (Pantanal, Caatinga, Cerrado, Atlantic Rainforest, and Amazon) previously characterized as Z3 or mixed infection (TcI-Z3) by mini-exon gene PCR. To identify TcIII and TcIV genotypes, we applied restriction fragment length polymorphism analysis to the PCR-amplified histone 3 gene. DTUs TcIII and TcIV were identified in single and mixed infections from wide dispersion throughout five Brazilian biomes studied, with TcIV being the most common. Pantanal was the biome that displayed the largest number of samples characterized as TcIII and TcIV in single and mixed infections, followed by Atlantic Rainforest and Amazon. Species from the Didelphimorphia order displayed the highest frequency of infection and were found in all five biomes. We report, for the first time, the infection of a species of the Artiodactyla order by DTU TcIII. In addition, we describe new host species: five mammals (marsupials and rodents) and two genera of Hemiptera. Our data indicate that DTUs TcIII and TcIV are more widespread and infect a larger number of mammalian species than previously thought. In addition, they are transmitted in restricted foci and cycles, but in different microhabitats and areas with distinct ecological profiles. Finally, we show that DTUs TcIII and TcIV do not present any specific association with biomes or host species. Copyright © 2017. Published by Elsevier B.V.

Assessing activation of hepatic stellate cells by (99m)Tc-3PRGD2 scintigraphy targeting integrin αvβ3: a feasibility study.

PubMed

Zhang, Xin; Xin, Jun; Shi, Yu; Xu, Weina; Yu, Shupeng; Yang, Zhiguang; Liu, Changping; Cao, Li; Guo, Qiyong

2015-03-01

Hepatic stellate cell (HSC) activation, which is accompanied by increased expression of integrin αvβ3, is an important factor in liver fibrogenesis. Molecular imaging targeting the integrin αvβ3 could provide a non-invasive method for evaluating the expression and the function of the integrin αvβ3 on the activated HSCs (aHSCs) in the injured liver, and then provide important prognostic information. (99m)Tc-3PRGD2 is such a radiotracer specific for integrin αvβ3. In this study, we aimed to compare the differences in liver uptake and retention of the (99m)Tc-3PRGD2 between normal liver and injured liver to evaluate the feasibility of (99m)Tc-3PRGD2 scintigraphy for this purpose. We used planar scintigraphy to assess changes in integrin αvβ3 binding of intravenously-administered (99m)Tc-3PRGD2 in the livers of rats with thioacetamide (TAA)-induced liver fibrosis compared with the controls. We co-injected cold c(RGDyK) with (99m)Tc-3PRGD2 to assess the specific binding of the radiotracer. We performed Sirius red staining to assess liver fibrosis, immunofluorescent colocalization to identify the location of integrin αvβ3 expressed in the fibrotic liver, and we measured protein and messenger RNA expression of integrin αvβ3 and alpha smooth muscle actin (α-SMA) in the control and fibrotic livers. The fibrotic livers showed enhanced (99m)Tc-3PRGD2 uptake and retention. The radiotracer was demonstrated to bind specifically with the integrin αvβ3 mainly expressed on the aHSCs. The liver-to-heart ratio at 30 min post-injection was higher in the fibrotic livers than in the control livers (TAA, 1.98±0.08 vs. control, 1.50±0.12, p<0.01). The liver t1/2 was longer than in the controls (TAA, 27.07±10.69 min vs. control, 12.67±4.10 min, p<0.01). The difference of heart t1/2 between the two groups was not statistically significant (TAA, 3.13±0.63 min vs. control, 3.41±0.77 min, p=0.94). (99m)Tc-3PRGD2 molecular imaging can provide a non-invasive method for

The discovery of robust magnetism in a technetium oxide: The structure of CaTcO3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Avdeev, Maxim; Thorogood, Gordon J.; Carter, Melody L.

The technetium perovskite CaTcO{sub 3} has been synthesized. Combining synchrotron X-ray and neutron diffraction, we found that CaTcO{sub 3} is an antiferromagnetic with a surprisingly high Neel temperature of 800 K. The transition to the magnetic state does not involve a structural change, but there is obvious magnetostriction. Electronic structure calculations confirm the experimental results.

Interlayer electron-phonon coupling in WSe2/hBN heterostructures

NASA Astrophysics Data System (ADS)

Jin, Chenhao; Kim, Jonghwan; Suh, Joonki; Shi, Zhiwen; Chen, Bin; Fan, Xi; Kam, Matthew; Watanabe, Kenji; Taniguchi, Takashi; Tongay, Sefaattin; Zettl, Alex; Wu, Junqiao; Wang, Feng

2017-02-01

Engineering layer-layer interactions provides a powerful way to realize novel and designable quantum phenomena in van der Waals heterostructures. Interlayer electron-electron interactions, for example, have enabled fascinating physics that is difficult to achieve in a single material, such as the Hofstadter's butterfly in graphene/boron nitride (hBN) heterostructures. In addition to electron-electron interactions, interlayer electron-phonon interactions allow for further control of the physical properties of van der Waals heterostructures. Here we report an interlayer electron-phonon interaction in WSe2/hBN heterostructures, where optically silent hBN phonons emerge in Raman spectra with strong intensities through resonant coupling to WSe2 electronic transitions. Excitation spectroscopy reveals the double-resonance nature of such enhancement, and identifies the two resonant states to be the A exciton transition of monolayer WSe2 and a new hybrid state present only in WSe2/hBN heterostructures. The observation of an interlayer electron-phonon interaction could open up new ways to engineer electrons and phonons for device applications.

Exercise Desert Rock VII. Operation Order Number 1. Army, Camp Desert Rock, Nevada

DTIC Science & Technology

1957-05-11

te locetod at the rear of the serial. Vehic ’es * td ii break down durirG the mov ant to Uhe observer area will be pushed to the side of the road ni...26th TC Bn,Hq & IHq co 2d TC Truck Co (Peo) 38th TC Co (Hv) 351st TC Co (Red) TC Provisional Aircraft Uaint Det DESE,t- ROCK PROJECTS Project 50.3

Effect of different thickness h-BN coatings on interface shear strength of quartz fiber reinforced Sisbnd Osbnd Csbnd N composite

NASA Astrophysics Data System (ADS)

Wang, Shubin; Zheng, Yu

2014-02-01

Hexagonal boron nitride (h-BN) coatings with different thickness were prepared on quartz fibers to improve mechanical properties of quartz fiber reinforced Sisbnd Osbnd Csbnd N composite. Scanning electron microscopy (SEM), push-out test and single edge notched beam (SENB) in three point bending test were employed to study morphology, interface shear strength and fracture toughness of the composite. The results showed that h-BN coatings changed the crack growth direction and weaken the interface shear strength efficiently. When the h-BN coating was 308.2 nm, the interface shear strength was about 5.2 MPa, which was about one-quarter of that of the sample without h-BN coatings. After the heating process for obtaining composite, the h-BN nanometer-sized grains would grow up to micron-sized hexagonal grains. Different thickness h-BN coatings had different structure. When the coatings were relatively thin, the hexagonal grains were single layer structure, and when the coatings were thicker, the hexagonal grains were multiple layer structure. This multiple layer interface phase would consume more power of cracks, thus interface shear strength of the composite decreased steadily with the increasing of h-BN coatings thickness. When the coating thickness was 238.8 nm, KIC reaches the peak value 3.8 MPa m1/2, which was more than two times of that of composites without h-BN coatings.

Flattening and manipulation of the electronic structure of h-BN/Rh(111) nanomesh upon Sn intercalation

NASA Astrophysics Data System (ADS)

Sugiyama, Yuya; Bernard, Carlo; Okuyama, Yuma; Ideta, Shin-ichiro; Tanaka, Kiyohisa; Greber, Thomas; Hirahara, Toru

2018-06-01

We have deposited Sn on corrugated hexagonal boron nitride (h-BN) nanomeshs formed on Rh(111) and found that Sn atoms are intercalated between h-BN and Rh, flattening the h-BN. Our reflection high-energy electron diffraction (RHEED) analysis showed that the average in-plane lattice constant of h-BN increases due to the loss of the corrugation. Furthermore, electronic structure measurements based on angle-resolved photoemission spectroscopy (ARPES) showed that the h-BN π band width increases significantly while the σ band width does not change as much. These behaviors were partly different from previous reports on the intercalation of h-BN/Rh system. Our results offer a novel, simple method to control the electronic structure of h-BN.

In Vitro/In Vivo Evaluation of Radiolabeled [(99m)Tc(CO)3](+)-Hydroxyurea and Fluorescein Isothiocyanate-Hydroxyurea.

PubMed

Yilmaz, Baris; Teksoz, Serap; Kilcar, Ayfer Yurt; Ucar, Eser; Ichedef, Cigdem; Medine, Emin Ilker; Ari, Kadir

2016-02-01

The aim of current study is to examine hydroxyurea (HU), which is an antineoplastic drug used for the treatment of leukemia, sickle-cell disease, HIV, psoriasis, thrombocythemia, and various neoplastic diseases in two aspects. The active ingredient hydroxyurea was obtained by purification of the capsule form drug, commercially named as HYDREA. Then, [(99m)Tc(CO)3](+)core radiolabeling with HU was performed as first aspect. Quality control studies of (99m)Tc(CO)3-HU complex were performed by thin-layer radiochromatography and high-performance liquid radiochromatography methods. The results demonstrated that the radiolabeling yield was quite high (98.43% ± 2.29%). Also, (99m)Tc(CO)3-HU complex has good stability during the 24-hour period. Biological behavior of (99m)Tc(CO)3-HU complex is evaluated by biodistribution studies on Wistar Albino rats. Fluorescein isothiocyanate (FITC) labeling of HU was performed as second aspect. Fluorometric evaluation of binding efficacy and fluorescence imaging studies on MCF7 and Hela cell lines were carried out. It was thought that the knowledge achieved in this study would contribute to using (99m)Tc(CO)3-HU complex as an imaging agent, which inhibits the DNA synthesis selectively, by inhibiting ribonucleotide reductase enzyme. It was observed that FITC-HU has noteworthy incorporation on both cell lines.

Hybrid surface-phonon-plasmon polariton modes in graphene/monolayer h-BN heterostructures.

PubMed

Brar, Victor W; Jang, Min Seok; Sherrott, Michelle; Kim, Seyoon; Lopez, Josue J; Kim, Laura B; Choi, Mansoo; Atwater, Harry

2014-07-09

Infrared transmission measurements reveal the hybridization of graphene plasmons and the phonons in a monolayer hexagonal boron nitride (h-BN) sheet. Frequency-wavevector dispersion relations of the electromagnetically coupled graphene plasmon/h-BN phonon modes are derived from measurement of nanoresonators with widths varying from 30 to 300 nm. It is shown that the graphene plasmon mode is split into two distinct optical modes that display an anticrossing behavior near the energy of the h-BN optical phonon at 1370 cm(-1). We explain this behavior as a classical electromagnetic strong-coupling with the highly confined near fields of the graphene plasmons allowing for hybridization with the phonons of the atomically thin h-BN layer to create two clearly separated new surface-phonon-plasmon-polariton (SPPP) modes.

Imaging prostate cancer (PCa) with [99m Tc(CO)3 ]finasteride dithiocarbamate.

PubMed

Shah, Syed Qaiser; Gul-E-Raana; Uddin, Ghias

2018-06-15

This investigation aimed to modify finasteride (1) to finasteride dithiocarbamate (2) for subsequent synthesis of the rhenium analogue (3) and [ 99m Tc]tricarbonyl complexes (4), to assess its prostate cancer (PCa) targeting potential in a rat model. To validate the identity of (4), reference (3) has been synthesized by using fac-[Net 4 ] 2 [ReBr 3 (CO) 3 ] precursor and characterized by 1 H-NMR, 13 C-NMR, ESI-MS, and elemental analysis. The analogue (4) was synthesized by using fac-[ 99m Tc(H 2 O) 3 (CO) 3 ] + precursor, and its structure was confirmed by comparative HPLC by using (3) as a reference. Further, the suitability of (4) as a PCa imaging agent was investigated in vitro and in vivo. At room temperature, (4) had ≥99% radiochemical purity and remained ≥84% stable in serum. In preclinical studies, biodistribution of (4) in histopathologically established rat model showed adequately high in vivo uptake in the prostate attracting the possibility of using it for noninvasive imaging of PCa. Copyright © 2018 John Wiley & Sons, Ltd.

An antagonistic monoclonal antibody (B-N6) specific for the human neurotensin receptor-1.

PubMed

Ovigne, J M; Vermot-Desroches, C; Lecron, J C; Portier, M; Lupker, J; Pecceu, F; Wijdenes, J

1998-06-01

The neuropeptide neurotensin (NT) interacts with two types of human receptors (hNTR) termed hNTR-1 and hNTR-2. This study describes a monoclonal antibody (MAb) specific for hNTR-1, B-N6. This MAb binds specifically to hNTR-1, but not to hNTR-2 transfected CHO cells. B-N6 and NT display a reciprocal competition and react in a similar way to trypsin, suggesting that the B-N6 epitope is at or close to the NT binding site on the third extracellular loop. Unlike B-N6, NT induces hNTR-1 internalization. Although neither NT-FITC nor B-N6 binding was detected by flow cytometry on different human cells, specific mRNA expression for hNTR-1 was detected in these cells. In CHO cells expressing hNTR-1 and a luciferase gene coupled to the krox24 reporter, B-N6 and the antagonist SR 48692 inhibited NT-induced intracellular activation of krox24 in a dose-dependent manner. From these results it is concluded that B-N6 is an antagonistic anti-hNTR-1 MAb.