An improved synthesis of 4-[18F]-ADAM, a potent serotonin transporter imaging agent

International Nuclear Information System (INIS)

Huang, Y.-Y.; Huang, W.-S.; Chu, T.-C.; Shiue, C.-Y.

2009-01-01

An improved synthesis of N,N-dimethyl-2-(2-amino-4-[ 18 F]fluorophenylthio)benzylamine (4-[ 18 F]-ADAM, 2) as a potent serotonin transporter (SERT) imaging agent is described. Molecular orbital (MO) calculation predicts that N,N-dimethyl-2- (2-nitro-4-trimethylammoniumtrifluoromethanesulfonylphenylthio)benzamide (8) is probably a better precursor than N,N-dimethyl-2-(2,4-dinitrophenylthio)benzylamine (1) for preparing 2. Radioligand 2 was synthesized by the reaction of either precursor 1 or precursor 8 with K[ 18 F]/K 2.2.2 at 120 deg. C followed by reduction with BH 3 at 80 deg. C. The radiochemical yield (EOB) of 2 synthesized from precursor 1 and 8 was 5.7±2.4% (n=6) and 14.8±4.0% (n=5), respectively, in a synthesis time of 120 min from EOB. The specific activity of 2 was 3 Ci/μmol or 111 GBq/μmol (EOB). Thus, this new synthetic method has significantly improved the radiochemical yield of 4-[ 18 F]-ADAM and makes this radioligand more accessible to PET Centers without a cyclotron.

Comparison of [{sup 18}F]FHBG and [{sup 14}C]FIAU for imaging of HSV1-tk reporter gene expression: adenoviral infection vs stable transfection

Energy Technology Data Exchange (ETDEWEB)

Min, Jung-Jun; Iyer, Meera [The Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, B3-399A BRI 700 Westwood Plaza, CA 90095-1770, Los Angeles (United States); Gambhir, Sanjiv S. [The Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, B3-399A BRI 700 Westwood Plaza, CA 90095-1770, Los Angeles (United States); Department of Radiology, Bio-X Program, Stanford University, Stanford, California (United States)

2003-11-01

Earlier studies involving comparison of different reporter probes have shown conflicting results between pyrimidine nucleosides [e.g., 2'-fluoro-2'-deoxy-1-{beta}-d-arabinofuranosyl-5-iodouracil (FIAU)] and acycloguanosine derivatives [e.g., penciclovir (PCV), 9-(4-fluoro-3-hydroxymethylbutyl)guanine (FHBG)]. We hypothesized that this reported discrepancy may be related to how the reporter gene is delivered to the cells - stably transfected vs adenoviral infection. We directly compared the uptake characteristics of [{sup 18}F]FHBG, [{sup 3}H]PCV, and [{sup 14}C]FIAU in cell culture and in vivo using an adenoviral mediated gene transfer model and stably transfected cells. We further compared the uptake of three reporter probes using both HSV1-tk and a mutant HSV1-sr39tk expressing cells to assess the optimal reporter probe/reporter gene combination. [{sup 14}C]FIAU accumulation was greater than that of [{sup 3}H]PCV and [{sup 18}F]FHBG in control cells and in HSV1-tk stably transfected cells (P<0.001). After infection of C6 cells with AdCMV-HSV1-tk (1.5 x 10{sup 8} pfu), [{sup 18}F]FHBG and [{sup 3}H]PCV accumulation was significantly greater than that of [{sup 14}C]FIAU (P<0.01). [{sup 18}F]FHBG and [{sup 3}H]PCV accumulated to a significantly greater extent than [{sup 14}C]FIAU in C6-stb-sr39tk+ and AdCMV-HSV1-sr39tk infected C6 cells (P<0.001). Results from the nude mice supported the results in cell culture. [{sup 14}C]FIAU led to significantly higher %ID/g in C6-stb-tk+ xenografts than [{sup 18}F]FHBG (P<0.05); however, compared with [{sup 14}C]FIAU, [{sup 18}F]FHBG led to as high %ID/g in HSV1-tk expressing hepatocytes and to significantly greater %ID/g in C6-stb-sr39tk+ xenografts and HSV1-sr39tk expressing hepatocytes. Dynamic sequential images showed that [{sup 18}F]FHBG was well retained in HSV1-sr39tk expressing cells (C6-stb-sr39tk+) for at least 4 h after injection, while it was rapidly cleared from HSV1-tk expressing cells (MH3924A

Specific features of precipitation hardening of austenitic steels with various base. 2. Kinetics and mechanism of carbide precipitation

International Nuclear Information System (INIS)

Kositsyna, I.I.; Sagaradze, V.V.; Khakimova, O.N.

1997-01-01

Electron microscopic studies were carried out to determine the kinetics and mechanisms of precipitation hardening in Fe-Mn, Fe-Mn-Cr, Fe-Cr-Mn-N, Fe-Cr-Ni and Fe-Ni base stainless steels (45G20M2F2, 50Kh16G15N6M2F2, 45Kh18N10G10M2F2, 40Kh18Ni18M2F2, 45N26M2F2). The steels were heat treated under various conditions. It is revealed that in manganese steels the particles of vanadium carbide nucleate according to homogeneous mechanism at all aging temperatures (600-750 deg C). The presence of chromium in the matrix promotes the transition to heterogeneous mechanism of carbide nucleation and growth. With nickel content increasing the plasticity of precipitation hardened steels gets better due to more intense diffusion of atoms and vacancies to grain boundaries and, hence, the widening of near-boundary zones free of carbide particles

Low cycle fatigue properties of CLAM steel at 823 K

Energy Technology Data Exchange (ETDEWEB)

Hu, Xue [Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang 110016 (China); University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049 (China); Huang, Lixin [Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang 110016 (China); State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao 066004 (China); Yan, Wei; Wang, Wei [Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang 110016 (China); Sha, Wei [School of Planning, Architecture and Civil Engineering, Queen' s University Belfast, Belfast BT9 5AG (United Kingdom); Shan, Yiyin, E-mail: yyshan@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang 110016 (China); Yang, Ke, E-mail: kyang@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang 110016 (China)

2014-09-08

China Low Activation Martensitic (CLAM) steel is considered to be the main candidate material for the first wall components of future fusion reactors in China. In this paper, the low cycle fatigue (LCF) behavior of CLAM steel is studied under fully reversed tension–compression loading at 823 K in air. Total strain amplitude was controlled from 0.14% to 1.8% with a constant strain rate of 2.4×10{sup −3} s{sup −1}. The corresponding plastic strain amplitude ranged from 0.023% to 1.613%. The CLAM steel displayed continuous softening to failure at 823 K. The relationship between strain, stress and fatigue life was obtained using the parameters obtained from fatigue tests. The LCF properties of CLAM steel at 823 K followed Coffin–Manson relationship. Furthermore, irregular serration was observed on the stress–strain hysteresis loops of CLAM steel tested with the total strain amplitude of 0.45–1.8%, which was attributed to the dynamic strain aging (DSA) effect. During continuous cyclic deformation, the microstructure and precipitate distribution of CLAM steel changed gradually. Many tempered martensitic laths were decomposed into subgrains, and the size and number of M{sub 23}C{sub 6} carbide and MX carbonitride precipitates decreased with the increase of total strain amplitude. The response cyclic stress promoted the recovery of martensitic lath, while the thermal activation mainly played an important role on the growth of precipitates in CLAM steel at 823 K. In order to have a better understanding of high-temperature LCF behavior, the potential mechanisms controlling stress–strain response, DSA phenomenon and microstructure changes have also been evaluated.

CT-guided diagnostic interventions for classification of focal hepatic lesions: A comparison of 14 G- and 18 G-large bore cutting needles; CT-gesteuerte perkutane Biopsien zur Klassifizierung von fokalen Leberlaesionen: Vergleich zwischen 14 G- und 18 G-Stanzbiopsienadeln

Energy Technology Data Exchange (ETDEWEB)

Haage, P.; Piroth, W.; Staatz, G.; Adam, G.; Guenther, R.W. [Klinik fuer Radiologische Diagnostik, Universitaetsklinikum der RWTH Aachen (Germany)

1999-07-01

Purpose: Analysis and comparison of CT-guided 14- and 18-gauge cutting needle biopsies to accurately assess focal liver disease. Methods: The data of 272 CT-guided biopsies in 268 patients were evaluated retrospectively with regard to sensitivity, specificity and complication rate of the chosen needle caliber in differentiating between benign and malignant disease as well as in the ability to determine specific cell types in the various disorders. A 14-gauge (G) needle was used in 101 (37.1%) cases, in 18-g needle biopsy was performed in 171 (62.9%) cases. The Fisher exact test was employed for statistical analysis. Results: Cutting needle biopsy yielded sufficient histologic material in 267 of 272 (98.2%) cases. Correct diagnosis of malignancy was established in 178 of 191 (93.2%) lesions, 73 of 76 (96.1%) disorders were accurately defined as benign, resulting in an overall value of 94.0% (251 of 267). Of these 251 biopsies a definite histological diagnosis could be determined in 90.6% of the cases employing a 14 G needle and in 90.3% using an 18-g needle. The sensitivity, specificity and rate of complications were 94.8%, 92.0%%, 3.0% for the 14-g needle and 92.7%, 97.6%, 0.6% for the 18-g needle, respectively. There were no statistically significant differences with regard to the needle size. Conclusions: CT-guided biopsy of hepatic lesions with the 18-g biopsy needle is of equivalent diagnostic accuracy when compared with the 14-g needle. (orig.) [Deutsch] Ziel: Analyse und Vergleich CT-gesteuerter Fein- und Grobstanzbiopsien zur definitiven Abklaerung unklarer fokaler Leberveraenderungen. Methoden: Die Daten von insgesamt 272 CT-gefuehrten Punktionen an 268 Patienten wurden retrospektiv hinsichtlich Sensitivitaet, Spezifitaet und Komplikationsrate zur Dignitaetsbestimmung und Faehigkeit zur artdiagnostischen Einordnung unter Beruecksichtigung der Groesse der gewaehlten Punktionsnadel ueberprueft und ausgewertet. In 101 (37,1%) Faellen wurde eine 14 Gauge (G

18F-NaF PET/CT for the evaluation of temporomandibular joint disorder.

Science.gov (United States)

Suh, M S; Park, S H; Kim, Y-K; Yun, P-Y; Lee, W W

2018-04-01

To investigate the usefulness of a quantitative parameter (maximum standardised uptake value [SUVmax]) of 18 F-sodium fluoride (NaF) positron-emission tomography (PET)/computed tomography (CT) for the evaluation of temporomandibular joint (TMJ) disorder (TMD). Seventy-six TMD patients (male: female=14:62, age=40.3±17.1 years, bilateral: unilateral=40:36) with 152 TMJs were enrolled. The 18 F-NaF PET/CT parameter (SUVmax) was compared with the presence of TMJ arthralgia (arthralgic=86, non-arthralgic=66) and clinical subtypes based on the Research Diagnostic Criteria for TMD Axis I (TMD osteoarthritis=49, non-TMD osteoarthritis=67, and asymptomatic TMJ=36). Splint therapy was applied to 48 patients for 6 months without considering 18 F-NaF PET/CT findings. Post-splint therapy 18 F-NaF PET/CT was performed in 32 patients and clinical responses to the therapy were classified into improvement (n=33), no change (n=10), or aggravation (n=7) for 50 TMJs excluding asymptomatic TMJs (n=14). SUVmax was significantly greater in arthralgic TMJs than in non-arthralgic TMJs (6.62±3.56 versus 4.32±1.53, pchange in SUVmax was observed in improved (from 6.16±2.68 to 6.09±2.60, p=0.4915) and unchanged (from 6.46±4.19 to 6.77±4.32, p=0.3223) TMJs. 18 F-NaF PET/CT is a useful imaging tool for TMD evaluation because SUVmax showed a fair diagnostic performance for arthralgic TMJ and TMD osteoarthritis, and a correlation with the therapeutic response. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Radiosynthesis of F-18 PBR111, a selective radioligand for imaging the translocator protein (18 kDa) with PET

International Nuclear Information System (INIS)

Dolle, F.; Hinnen, F.; Damont, A.; Kuhnast, B.; Tavitian, B.; Fookes, C.; Pham, T.; Katsifis, A.; Tavitian, B.

2008-01-01

PBR111 (2-(6-chloro-2-(4-(3-fluoro-propoxy)phenyl)imidazo[1,2-a]pyridin-3-yl)-N, N-diethylacetamide) is a novel, reported, high-affinity and selective ligand for the translocator protein (18 kDa). PBR111 has been labelled with fluorine-18 (half-life: 109.8 min) using our Zymate-XP robotic system. The process involves (A) a simple one-step to syloxy-for-fluorine nucleophilic aliphatic substitution (performed at 165 degrees C for 5 min in DMSO using K[ 18 F]F-Kryptofix 222 and 6.8-7.6 μ mol of the corresponding tosylate as precursor for labelling) followed by (B) C-18 PrepSep cartridge pre-purification and(C) semi-preparative HPLC purification on a Waters Symmetry C-18. Up to 4.8 GBq (130 mCi) of [ 18 F]PBR111 could be obtained with specific radioactivities ranging from 74 to 148 GBq/μ mol (2-4 Ci/μ mol) in 75-80 min (HPLC purification and SepPak-based formulation included), starting from a 37.0 GBq (1.0 Ci) [ 18 F]fluoride batch. Overall non-decay-corrected isolated yields were 8-13% (13-21% decay-corrected). (authors)

Radiosynthesis of F-18 PBR111, a selective radioligand for imaging the translocator protein (18 kDa) with PET

Energy Technology Data Exchange (ETDEWEB)

Dolle, F.; Hinnen, F.; Damont, A.; Kuhnast, B.; Tavitian, B. [CEA, Serv Hosp Frederic Joliot, Inst Imagerie Biomed, LIME, F-91406 Orsay (France); Fookes, C.; Pham, T.; Katsifis, A. [Australian Nucl Sci and Technol Org, RRI, Lucas Heights, NSW 2234 (Australia); Tavitian, B. [INSERM, U803, F-91406 Orsay (France)

2008-07-01

PBR111 (2-(6-chloro-2-(4-(3-fluoro-propoxy)phenyl)imidazo[1,2-a]pyridin-3-yl)-N, N-diethylacetamide) is a novel, reported, high-affinity and selective ligand for the translocator protein (18 kDa). PBR111 has been labelled with fluorine-18 (half-life: 109.8 min) using our Zymate-XP robotic system. The process involves (A) a simple one-step to syloxy-for-fluorine nucleophilic aliphatic substitution (performed at 165 degrees C for 5 min in DMSO using K[{sup 18}F]F-Kryptofix 222 and 6.8-7.6 {mu} mol of the corresponding tosylate as precursor for labelling) followed by (B) C-18 PrepSep cartridge pre-purification and(C) semi-preparative HPLC purification on a Waters Symmetry C-18. Up to 4.8 GBq (130 mCi) of [{sup 18}F]PBR111 could be obtained with specific radioactivities ranging from 74 to 148 GBq/{mu} mol (2-4 Ci/{mu} mol) in 75-80 min (HPLC purification and SepPak-based formulation included), starting from a 37.0 GBq (1.0 Ci) [{sup 18}F]fluoride batch. Overall non-decay-corrected isolated yields were 8-13% (13-21% decay-corrected). (authors)

{sup 18}F-F.D.G. PET imaging of infection and inflammation: intestinal, prosthesis replacements, fibrosis, sarcoidosis, tuberculosis..; La TEP au {sup 18}F-FDG dans la pathologie inflammatoire et infectieuse: intestinale, prothetique, fibrose, sarcoidose, tuberculose..

Energy Technology Data Exchange (ETDEWEB)

Fernandez, A.; Cortes, M.; Caresia, A.P.; Juan, R. de; Vidaller, A.; Mana, J.; Martinez-Yelamos, S.; Gamez, C. [Hospital Universitari de Bellvitge, Service TEP-Centre IDI, Services de Medecine Interne, Barcelone (Spain)

2008-10-15

Nuclear medicine plays an important role in the evaluation of infection and inflammation. A variety of diagnostic methods are available for imaging this inflammation and infection, most notably computed tomography, {sup 68}Ga scintigraphy or radionuclide labeled leucocytes. Fluorine 18 fluorodeoxyglucose ({sup 18}F-F.D.G.) is a readily available radiotracer that offers rapid, exquisitely sensitive high-resolution images by positron emission tomography (PET). Inflammation can be acute or chronic, the former showing predominantly neutrophilic granulocyte infiltrates, whereas in the latter, macrophages predominate. F.D.G. uptake in infection is based on the fact that mononuclear cells and granulocytes use large quantities of glucose by way of the hexose monophosphate shunts. {sup 18}F-F.D.G. PET accurately helps diagnose spinal osteomyelitis, diabetic foot and in inflammatory conditions such as sarcoidosis and tuberculosis.(it appears to be useful for defining the extent of disease and monitoring response to treatment). {sup 18}F-F.D.G. PET can also help localize the source of fever of undetermined origin, thereby guiding additional testing. {sup 18}F-F.D.G. PET may be of limited usefulness in postoperative patients and in patients with a failed joint prosthesis or bowel inflammatory disease. In this review, we will focus on the role of {sup 18}F-F.D.G. PET in the management of patients with inflammation or suspected or confirmed infection.

^2H(^18F,p)^19F Study at 6 MeV/u

Science.gov (United States)

Kozub, R. L.; Nesaraja, C. D.; Moazen, B. H.; Scott, J. P.; Bardayan, D. W.; Blackmon, J. C.; Gross, C. J.; Shapira, D.; Smith, M. S.; Batchelder, J. C.; Brune, C. R.; Champagne, A. E.; Sahin, L.; Cizewski, J. A.; Thomas, J. S.; Davinson, T.; Woods, P. J.; Greife, U.; Jewett, C.; Livesay, R. J.; Ma, Z.; Parker, P. D.

2003-04-01

The degree to which the (p,α) and (p,γ) reactions destroy ^18F at temperatures ˜1-4 x 10^8 K is important for understanding the synthesis of nuclei in nova explosions and for using ^18F as a monitor of nova mechanisms in gamma ray astronomy. The reactions are dominated by low-lying proton resonances near the ^18F+p threshold (E_x=6.411 MeV excitation energy in ^19Ne). To gain further information about these resonances, we have used the inverse ^18F(d,p)^19F neutron transfer reaction at the Holifield Radioactive Ion Beam Facility to selectively populate corresponding mirror states in ^19F. Proton angular distributions were measured for states in ^19F in the excitation energy range 0-9 MeV. Results and implications for the ^18F+p reactions and nuclear structure will be presented. ^1Supported by DOE. ^2ORNL is managed by UT-Battelle, LLC, for the USDOE.

PET imaging of lung inflammation with [18F]FEDAC, a radioligand for translocator protein (18 kDa.

Directory of Open Access Journals (Sweden)

Akiko Hatori

Full Text Available PURPOSE: The translocator protein (18 kDa (TSPO is highly expressed on the bronchial and bronchiole epithelium, submucosal glands in intrapulmonary bronchi, pneumocytes and alveolar macrophages in human lung. This study aimed to perform positron emission tomography (PET imaging of lung inflammation with [(18F]FEDAC, a specific TSPO radioligand, and to determine cellular sources enriching TSPO expression in the lung. METHODS: An acute lung injury model was prepared by intratracheal administration of lipopolysaccharide (LPS to rat. Uptake of radioactivity in the rat lungs was measured with small-animal PET after injection of [(18F]FEDAC. Presence of TSPO was examined in the lung tissue using Western blot and immunohistochemical assays. RESULTS: The uptake of [(18F]FEDAC increased in the lung with the progress of inflammation by treatment with LPS. Pretreatment with a TSPO-selective ligand PK11195 showed a significant decrease in the lung uptake of [(18F]FEDAC due to competitive binding to TSPO. TSPO expression was elevated in the inflamed lung section and its level responded to the [(18F]FEDAC uptake and severity of inflammation. Increase of TSPO expression was mainly found in the neutrophils and macrophages of inflamed lungs. CONCLUSION: From this study we conclude that PET with [(18F]FEDAC may be a useful tool for imaging TSPO expression and evaluating progress of lung inflammation. Study on human lung using [(18F]FEDAC-PET is promising.

Contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography in immunoglobulin G4-related retroperitoneal fibrosis

International Nuclear Information System (INIS)

Sharma, Punit; Chatterjee, Piyali

2015-01-01

Immunoglobulin G4 (IgG4)-related disease encompasses a wide variety of immune disorders previously thought be distinct. IgG4-related retroperitoneal fibrosis is one such entity. Metabolic imaging with 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) can be useful in the management of IgG4-related retroperitoneal fibrosis. We here discuss the case of 63-year-old male with IgG4-related retroperitoneal fibrosis and the role, 18 F-FDG PET/CT played in his management

Canine study on myocardial ischemic memory with 18F-FDG PET/CT imaging

International Nuclear Information System (INIS)

Xie Boqia; Yang Minfu; Dou Kefei; Han Chunlei; Tian Yi; Zhang Ping; Yang Zihe; Yin Jiye; Wang Hao

2012-01-01

Objective: To explore whether the existence and duration of ischemia measured by dynamic 18 F-FDG PET/CT imaging correlated with the extent of myocardial ischemia in a canine model of myocardial ischemia-reperfusion. Methods: Canine coronary artery occlusion was carried out for 20 min (n=4) and for 40 min (n=4) followed by 24 h of open-artery reperfusion. All dogs underwent dynamic 18 F-FDG PET/CT and 99 Tc m -MIBI SPECT imaging at baseline and 1 h and 24 h after reperfusion.Quantitative analysis of myocardial 18 F-FDG uptake was performed using Carimas Core software,and the extraction ratio of 18 F-FDG (K) was calculated by the ratio of 18 F-FDG uptake rate in the ischemic area (k ischemia ) and normoperfused region (k normoperfused ). Echocardiographic data were also acquired between each PET/CT imaging study to detect the wall motion in the ischemic and normoperfused myocardium. Paired t test and non-parametric statistical tests, measured by SPSS 19.0, were used to analyze the data. Results: Coronary occlusion produced sustained, abnormal wall motion in the ischemic region for more than 1 h. Similar K values were demonstrated between the 20 min and 40 min groups at baseline (1.02 ±0.06 and 1.03 ±0.05, Z=-0.29, P>0.05). At 1 h after reperfusion, the reperfusion regions showed normal perfusion but with increased 18 F-FDG uptake, which was higher in the 40 min ischemic group than in the 20 min ischemic group (2.31 ±0.13 and 1.87 ±0.09, Z=-2.31, P<0.05). At 24 h after reperfusion, however, only the 40 min ischemic group showed slightly higher 18 F-FDG uptake than baseline (1.15 ± 0.02 and 1.03 ±0.05, t=4.32, P<0.05), whereas no significant difference was found in the 20 min ischemic group (1.05 ± 0.04 and 1.02 ± 0.06, t=0.87, P>0.05). Histological examination of the ischemic myocardium from both groups revealed neatly arranged cells without interstitial edema, hemorrhage nor inflammatory response. Conclusions: Myocardial 'ischemic memory' was

Doubling-resolution analog-to-digital conversion based on PIC18F45K80

Directory of Open Access Journals (Sweden)

Yueyang Yuan

2014-08-01

Full Text Available Aiming at the analog signal being converted into the digital with a higher precision, a method to improve the analog-to-digital converter (ADC resolution is proposed and described. Based on the microcomputer PIC18F45K80 in which the internal ADC modules are embedded, a circuit is designed for doubling the resolution of ADC. According to the circuit diagram, the mathematical formula for calculating this resolution is derived. The corresponding software and print circuit board assembly is also prepared. With the experiment, a 13 bit ADC is achieved based on the 12 bit ADC module predesigned in the PIC18F45K80.

Is subnanomolar binding affinity required for the in vivo imaging of acetylcholinesterase? Studies on 18F-labeled G379

International Nuclear Information System (INIS)

Lee, Sang-Yoon; Choe, Yearn Seong; Ryu, Eun Kyoung; Iimura, Yoichi; Choi, Yong; Lee, Kyung-Han; Kim, Byung-Tae

2006-01-01

Acetylcholinesterase (AChE) is an important cholinergic marker of Alzheimer's disease (AD) and shows reduced activity in postmortem AD brain tissues. 1-(4-Fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-fluoro-2-yl)methyl] piperidine (G379, ), an AChE inhibitor with a subnanomolar IC 5 (0.56 nM), was prepared as a 18 F-labeled radioligand ([ 18 F]) and evaluated in mice. Metabolism studies of [ 18 F] showed no metabolites in the mouse brain. Tissue distribution studies demonstrated its uniform regional distribution in the mouse brain, suggesting that this radioligand is not suitable for the in vivo imaging of AChE. This result along with reports on radiolabeled N-benzylpiperidine lactam benzisoxazole (IC 5 5 >1 nM) suggested that a subnanomolar IC 5 may not be the only important factor in determining the suitability of a radioligand for in vivo studies of AChE

PET with {sup 18}F-F.D.G. in the diagnosis and the evolutionary follow up of solitary plasmocytomas; La TEP au {sup 18}F-FDG dans le diagnostic et le suivi evolutif des plasmocytomes solitaires

Energy Technology Data Exchange (ETDEWEB)

Adib, S.; Huglo, D.; Steinling, M. [Hopital Huriez, CHU de Lille, Service de medecine nucleaire, 59 (France); Leleu, X.; Robu, D. [Hopital Huriez, CHU de Lille, service des maladies du sang, 59 (France)

2010-07-01

Purpose: evaluate the contribution of PET with {sup 18}F-F.D.G. in the diagnostic assessment, post therapy evaluation and evolutionary follow-up of solitary plasmocytomas. Conclusions: the PET with {sup 18}F-F.D.G. seems to be an efficient diagnostic tool in the staging of solitary plasmocytomas and allows also to detect infra clinical injuries unknown by other imaging techniques. (N.C.)

Peculiarities of welding procedure for the 05Kh12K14N5M5T-VD maraging stainless steel with strength higher 1500 MPa

International Nuclear Information System (INIS)

Pustovit, A.I.

1980-01-01

The effect of welding procedure of 05Kh12K14N5M5T-VD stainless steel on the properties of its welded joints is investigated. A new procedure of welding for pressure vessels made of this steel using Sv-03Kh15K14N5M3T-EL welding wire is suggested [ru

Vasculitis assessment with [{sup 18}F]F.D.G. positron emission tomography; Place de la tomographie par emission de positons (TEP) au [{sup 18}F]FDG dans l'exploration des vascularites

Energy Technology Data Exchange (ETDEWEB)

Liozon, E. [CHU Dupuytren, Services de Medecine Interne A, 87 - Limoges (France); Monteil, J. [CHU Dupuytren, Services de Medecine Nucleaire, 87 - Limoges (France)

2008-10-15

[{sup 18}F]fluorodeoxyglucose ({sup 18}F.D.G.) positron emission tomography (PET) is a noninvasive metabolic imaging modality that is well suited to the assessment of activity and extent of large vessel vasculitis, such as giant cell arteritis and Takayasu arteritis. PET could be more effective than magnetic resonance imaging in detecting the earliest stages of vascular wall inflammation. The visual grading of vascular [{sup 18}F]F.D.G. uptake makes it possible to discriminate arteritis from atherosclerosis, providing therefore high specificity. High sensitivity can be achieved provided scanning is performed during active inflammatory phase, preferably before starting corticosteroid treatment. Large scale prospective studies are needed to determine the exact value of PET imaging in assessing the large vessel vasculitis outcome and response to immunosuppressive treatment.

The system K2NbF7-K2TiF6-KCl

International Nuclear Information System (INIS)

Kamenskaya, L.A.; Matveev, A.M.

1984-01-01

Using visual-polythermal and thermographical methods the ternary system K 2 NbF 7 -K 2 TiE 6 -KCl has been studied. Crystallization fields of initial components and the field of solid solutions of double compounds K 3 NbClF 7 and K 3 TiClF 6 are outlined. Ternary eutectics at 654 deg C, having the composition K 2 NbF 6 -41, K 2 TiP 6 -41, KCl-18 mol.%, is determined. Potassium fluoroniobate and fluorotitanate form continuous solid solutions unstable in the presence of the third component, potassium chloride

Radiosynthesis of dimethyl-2-[{sup 18}F]-(fluoromethyl)-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate for L-type calcium channel imaging

Energy Technology Data Exchange (ETDEWEB)

Sadeghpour, H. [Nuclear Medicine Research Group, Agricultural, Medical and Industrial Research School (AMIRS), Karaj (Iran); Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran Univ. of Medical Sciences, Tehran (Iran); Jalilian, A.R.; Akhlaghi, M.; Mirzaei, M. [Nuclear Medicine Research Group, Agricultural, Medical and Industrial Research School (AMIRS), Karaj (Iran); Shafiee, A. [Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran Univ. of Medical Sciences, Tehran (Iran); Miri, R. [Medicinal and Natural Products Chemistry Research Center, Shiraz Univ. of Medical Sciences, Shiraz (Iran)

2008-07-01

Dimethyl 2-(fluoromethyl)-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 4a, a fluorinated nifedipine analog, has been shown to elicit significant calcium channel blocker activity using a guinea pig ileal longitudinal smooth muscle model. In order to perform biological studies for detection of L-type calcium channel distribution, we decided to prepare the [{sup 18}F]-labeled compound. The latter compound was prepared in no-carrier-added (n.c.a.) form from dimethyl 2-(bromomethyl)-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 2 in one step at 80 C in Kryptofix[222]/K[{sup 18}F]F and acetonitrile as a solvent in 15 min. Column chromatography afforded the radiochemically pure compound in 20 min. Radiochemical purity of the {sup 18}F-nifedipine was determined by RTLC and HPLC (> 98%) and specific activity of 21-48 GBq/{mu}mol (EOB). (orig.)

Fast and repetitive in-capillary production of [{sup 18}F]FDG

Energy Technology Data Exchange (ETDEWEB)

Wester, Hans-Juergen; Schoultz, Bent Wilhelm; Hultsch, Christina; Henriksen, Gjermund [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany)

2009-04-15

The increasing demand for radiopharmaceuticals to be provided reproducibly and flexibly with high frequency for clinical application and animal imaging would be better met by improved or even new strategies for automated tracer production. Radiosynthesis in microfluidic systems, i.e. narrow tubing with a diameter of approximately 50-500 {mu}m, holds promise for providing the means for repetitive multidose and multitracer production. In this study, the performance of a conceptually simple microfluidic device integrated into a fully automated synthesis procedure for in-capillary radiosynthesis (ICR) of clinical grade [{sup 18}F]FDG was evaluated. The instrumental set-up consisted of pumps for reagent and solvent delivery into small mixing chambers, {mu}-fluidic capillaries, in-process radioactivity monitoring, solid-phase extraction and on-column deprotection of the {sup 18}F-labelled intermediate followed by on-line formulation of [{sup 18}F]FDG. In-capillary{sup 18}F-fluorination of 2.1 {mu}mol 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulphonyl-beta-d-mannopyranose (TATM; precursor for [{sup 18}F]FDG) in acetonitrile (MeCN) at a flow rate of 0.3 ml/min within 40 s and subsequent on-line hydrolysis of the intermediate by treatment with 0.3 M NaOH for 1 min at 40 C resulted in a radiochemical yield of 88 {+-} 4% within <7 min. Reproducibility, robustness and suitability as a fast and efficient radiopharmaceutical research tool for {sup 18}F-fluorination was demonstrated by eight independent, sequentially performed ICRs which provided identical tracer quality (radiochemical purity >97%, MeCN <5 {mu}g/ml) and similar absolute yields (approximately 1.4 GBq). The described ICR process is a simple and efficient alternative to classic radiotracer production systems and provides a comparatively cheap instrumental methodology for the repetitive production of [{sup 18}F]FDG with remarkably high efficiency and high yield under fully automated conditions. Although the results

S-factor of 14 N (α, γ)18 F reaction at low-energies

Science.gov (United States)

Khalili, H.

2018-06-01

The astrophysical S-factor of the 14 N (α, γ)18 F reaction has been studied at range of bombarding energy 1-1.30 MeV. The 14 N (α, γ)18 F process is important in low energy astrophysics so that a possible source of energy in massive stars which have spent their hydrogen cycle. Using the Wood-saxon potential model, we have been calculated non resonances the astrophysical S-factors for the E 2 transition and our results for Eα = 0.0 MeV is S ≈ 0.5 MeV.b where from experimental is measured to Eα = 0.0 is S ≈ o . 7 MeV.b (Couch et al., 1971) that in comparison with our data good agreement is achieved for the astrophysical S-factor of this process.

Synthesis of 6-[18F]fluoro-PBR28, a novel radiotracer for imaging the TSPO 18 kDa with PET

International Nuclear Information System (INIS)

Damont, A.; Boisgard, R.; Kuhnast, B.; Lemee, F.; Raggiri, G.; Tavitian, B.; Dolle, F.; Boisgard, R.; Tavitian, B.; Scarf, A.M.; Scarf, A.M.; Kassiou, M.; Da Pozzo, E.; Martini, C.; Selleri, S.; Kassiou, M.; Tavitian, B.; Kassiou, M.

2011-01-01

6-Fluoro-PBR28 (N-(6-fluoro-4-phenoxypyridin-3-yl)-N-(2-methoxybenzyl)acetamide), a fluorinated analogue of the recently developed TSPO 18 kDa ligand PBR28, was synthesized and labelled with fluorine- 18. 6-Fluoro-PBR28 and its 6-chloro/6-bromo counterparts were synthesized in six chemical steps and obtained in 16%, 10% and 19% overall yields, respectively. Labelling with fluorine-18 was performed in one single step (chlorine/bromine-for-fluorine heteroaromatic substitution) using a Zymate-XP robotic system affording HPLC-purified, ready-to-inject, 6-[ 18 F]fluoro-PBR28 (≥95% radiochemically pure). Non decay-corrected overall yields were 9-10% and specific radioactivities ranged from 74 to 148 GBq/μmol. In vitro binding experiments, dynamic μPET studies performed in a rat model of acute neuro-inflammation (unilaterally, AMPA-induced, striatum-lesioned rats) and ex vivo autoradiography on the same model demonstrated the potential of 6-[ 18 F]fluoro-PBR28 to image the TSPO 18 kDa using PET. (authors)

PET/CT studies of multiple myeloma using {sup 18}F-FDG and {sup 18}F-NaF: comparison of distribution patterns and tracers' pharmacokinetics

Energy Technology Data Exchange (ETDEWEB)

Sachpekidis, Christos [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); German Cancer Research Center, Medical PET Group - Biological Imaging Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Goldschmidt, Hartmut; Hose, Dirk [University of Heidelberg, Medical Clinic V, Heidelberg (Germany); National Center for Tumor Diseases Heidelberg, Heidelberg (Germany); Pan, Leyun; Cheng, Caixia; Dimitrakopoulou-Strauss, Antonia [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); Kopka, Klaus [German Cancer Research Center, Division of Radiopharmaceutical Chemistry, Heidelberg (Germany); Haberkorn, Uwe [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); University of Heidelberg, Division of Nuclear Medicine, Heidelberg (Germany)

2014-07-15

following mean values: SUV{sub aver} = 5.1, k{sub 1} = 0.37 (1/min), k{sub 3} = 0.10 (1/min), V{sub B} = 0.06, influx = 0.04 (1/min), FD = 1.28; the respective values for {sup 18}F-NaF were SUV{sub average} = 10.7, k{sub 1} = 0.25 (1/min), k{sub 3} = 0.34 (1/min), V{sub B} = 0.02, influx = 0.10 (1/min), FD = 1.37. Apart from the correlation between V{sub B} of {sup 18}F-FDG and k{sub 1} of {sup 18}F-NaF (r = 0.54), no other significant correlation was observed between the two tracers' kinetic parameters. We found a significant correlation between FD and SUV{sub average} (r = 0.93), FD and SUV{sub max} (r = 0.80), FD and influx (r = 0.85), as well as between influx and SUV{sub average} (r = 0.74) for {sup 18}F-FDG. In {sup 18}F-NaF we observed the most significant correlations between FD and SUV{sub average} (r = 0.97), FD and SUV{sub max} (r = 0.87), and between influx and k{sub 1} (r = 0.72). The combined use of {sup 18}F-FDG PET/CT and {sup 18}F-NaF PET/CT provides different molecular information regarding the biological processes that take place in a MM osseous lesion. {sup 18}F-FDG PET/CT proved to be a more specific biomarker than {sup 18}F-NaF PET/CT in multiple myeloma skeletal assessment. (orig.)

The improved syntheses of 5-substituted 2'-[18F]fluoro-2'-deoxy-arabinofuranosyluracil derivatives ([18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU) using a multistep one-pot strategy

International Nuclear Information System (INIS)

Cai Hancheng; Li Zibo; Conti, Peter S.

2011-01-01

Introduction: We and others have previously reported a four-step radiosynthesis of a series of 2'-deoxy-2'-[ 18 F]fluoro-5-substituted-1-β-D-arabinofuranosyluracil derivatives including [ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU as thymidine derivatives for tumor proliferation and/or reporter gene expression imaging with positron emission tomography (PET). Although the radiosynthesis has been proven to be reproducible and efficient, this complicated multistep reaction is difficult to incorporate into an automated cGMP-compliant radiosynthesis module for routine production. Recently, we have developed a simple and efficient one-pot method for routine production of [ 18 F]FMAU. In this study, we studied the feasibility of radiosynthesizing [ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU using this newly developed method. Methods: Similar to the radiosynthesis of [ 18 F]FMAU, 5-substituted 2'-[ 18 F]fluoro-2'-deoxy-arabinofuranosyluracil derivatives ([ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU) were synthesized in one-pot radiosynthesis module in the presence of Friedel-Crafts catalyst TMSOTf and HMDS. Results: This one-pot radiosynthesis method could be used to produce [ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU. The overall radiochemical yields of these tracers varied from 4.1%±0.8% to 10.1%±1.9% (decay-corrected, n=4). The overall reaction time was reduced from 210 min to 150 min from the end of bombardment, and the radiochemical purity was >99%. Conclusions: The improved radiosyntheses of [ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU have been achieved with reasonable yields and high purity using a multistep one-pot method. The synthetic time has been reduced, and the reaction procedures have been significantly simplified. The success of this approach may make PET tracers [ 18 F]FAU, [ 18 F

Ductile fracture of two-phase welds under 77K. [Steel-EhP810, steel-EhP666, steel-08Kh18N10T, steel-EhP659-VI, steel-chP810

Energy Technology Data Exchange (ETDEWEB)

Yushchenko, K.A.; Voronin, S.A.; Pustovit, A.I.; Shavel' , A.V.

The effect of the type of welding and fillers on crack resistance of welded joints high-strength steel EhP810 and its various compounds with steels EhP666, 08Kh18N10T has been studied. For the welding of steel EhP810 with steels EhP810, EhP666, 08Kh18N10T electron-beam, automatic, argon tungsten arc with non-consumable electrode with various fillers, as well as argon metal-arc welding with consumable electrode, were used. It is shown, that for a joint, made by electron-beam welding, parameters sigmasub(u), Ksub(IcJ), KCV are higher than for a joint of a similar phase structure made using filler wire EhP659-VI. It is explained by the fact, that during electron-beam welding joint metal refining takes place, which removes gases. In welded joints of chP810 steel, having joints with austenitic structure, characteristic of crack resistance Ssub(c) increases by more than 0.2 mm in contrast to two-phase joints, which conventional yield strength at 77 K exceeds 1000 MPa. It is worth mentioning, that for other classes of steels formation of two-phase structure of joint increases welded joint resistance to brittle fracture. It is possible to obtain the required structure of joint with assigned level of resistance to brittle fracture by means of the use of different fillers, optimum and welding procedure, regulating the part of the basic metal in joint content.

Preliminary design of a 150 kJ repetitive plasma focus for the production of 18-F

Science.gov (United States)

Sumini, Marco; Mostacci, Domiziano; Rocchi, Federico; Frignani, Michele; Tartari, Agostino; Angeli, Ergisto; Galaverni, Dario; Coli, Ugo; Ascione, Bernardino; Cucchi, Giorgio

2006-06-01

Experiments in the past five years have demonstrated production of short-lived radioisotopes with a Plasma Focus device, using the so-termed Endogenous Mode. So far radioisotope activities of only a few microcuries have been obtained from single discharges in small scale Plasma Focus machines (capacitor bank energies of approximately 7 kJ). It is expected that higher activities could be obtained with larger bank energies, operating at high pulse repetition rates, e.g. 1 Hz. However, many scientific and technological issues must be addressed for a high-energy Plasma Focus device to run at one pulse per second. Aim of this paper is to present preliminary results pertaining to the plasma, electrical, fluid-dynamical, thermal, material and mechanical design of a 150 kJ Plasma Focus, capable of a repetition rate of 1 Hz, that will be operated at 30 kV with a 350 μF capacitor bank and a maximum total current of 1.5 MA. This device will be used to breed 18-F for the synthesis of drugs used in positron-emission medical examinations, such as FDG for PET.

Preliminary design of a 150 kJ repetitive plasma focus for the production of 18-F

International Nuclear Information System (INIS)

Sumini, Marco; Mostacci, Domiziano; Rocchi, Federico; Frignani, Michele; Tartari, Agostino; Angeli, Ergisto; Galaverni, Dario; Coli, Ugo; Ascione, Bernardino; Cucchi, Giorgio

2006-01-01

Experiments in the past five years have demonstrated production of short-lived radioisotopes with a Plasma Focus device, using the so-termed Endogenous Mode. So far radioisotope activities of only a few microcuries have been obtained from single discharges in small scale Plasma Focus machines (capacitor bank energies of approximately 7 kJ). It is expected that higher activities could be obtained with larger bank energies, operating at high pulse repetition rates, e.g. 1 Hz. However, many scientific and technological issues must be addressed for a high-energy Plasma Focus device to run at one pulse per second. Aim of this paper is to present preliminary results pertaining to the plasma, electrical, fluid-dynamical, thermal, material and mechanical design of a 150 kJ Plasma Focus, capable of a repetition rate of 1 Hz, that will be operated at 30 kV with a 350 μF capacitor bank and a maximum total current of 1.5 MA. This device will be used to breed 18-F for the synthesis of drugs used in positron-emission medical examinations, such as FDG for PET

{sup 18}F-F.D.G. PET for staging and monitoring of solitary plasmocytomas;La TEP au {sup 18}F-FDG dans le diagnostic et le suivi evolutif des plasmocytomes solitaires

Energy Technology Data Exchange (ETDEWEB)

Adib, S.; Robua, D.; Huglo, D.; Steinling, M. [CHU de Lille, rue Michel-Polonovski, Service de medecine nucleaire, hopital Claude-Huriez, 59 - Lille (France); Robua, D.; Leleu, X. [CHU de Lille, rue Michel-Polonovski, Service des maladies du sang, hopital Claude-Huriez, 59 - Lille (France)

2010-02-15

Aim: To assess the role of [{sup 18}F]F.D.G.-PET in solitary plasmocytomas with regards to staging, therapeutic follow-up and monitoring. Patients and methods. Twenty consecutive patients were included in the present study when following conditions were met: (1) solitary plasmocytomas histologically confirmed (bone, n = 16; extramedullary, n = 4); (2) [{sup 18}F]F.D.G.-PET scan from July 2004 to April 2009. The clinical follow-up was over than 2 years for 13 patients. Ten patients underwent a post-therapy PET scan. PET scans were visually analysed. Results. PET scan enabled confirmation of all main lesions (sensitivity: 100%) and also detected infra-clinical lesions in eight cases. Follow-up for more than 2 years showed a progression disease into myeloma in five from six cases (83%) with infra clinical lesions at the baseline PET scan. Among 10 patients who underwent post-therapeutic PET scan, six experienced a complete response at the main lesion site and four experienced a partial response. Conclusion: F.D.G.-PET may play an important role in plasmocytomas staging and enables detection of smaller lesions (otherwise undetected). (authors)

18F-fluorination by crown ether-metal fluoride

International Nuclear Information System (INIS)

Irie, T.; Fukushi, K.; Ido, T.; Kasida, Y.; Nozaki, T.

1982-01-01

18 F-Fluorination by ''naked'' 18 F - anion produced by complexing anhydrous K 18 F, which was prepared from aqueous 18 F, with 18 -Crown-6 was described for preparing 18 F-21-fluoroprogesterone. In order to find out optimum conditions in this labelling method, various factors were investigated such as the solubility of KF in organic solvents containing 18 -Crown-6 and its reactivity for the nucleophilic displacement of 21-mesylate of progesterone. Chloroform was a good solvent in solubilization of KF and its reactivity. Problems in this labelling procedure were also examined, such as a supporter for transferring the labelled anhydrous K 18 F and reaction vessels. Use of a Teflon reaction vessel resulted in a good radiochemical yield based on the starting activity of $ 18 water. (author)

Preclinical incorporation dosimetry of (+)-[18F) flubatine in piglets

International Nuclear Information System (INIS)

Sattler, B.; Patt, M.; Sabri, O.; Kranz, M.; Donat, C.K.; Deuther-Conrad, W.; Fischer, S.; Brust, P.; Sattler, T.; Smits, R.; Hoepping, A.; Steinbach, J.

2015-01-01

Full text of publication follows. Aim: (+)-[ 18 F] flubatine is the mirror image isomer of (-)-[ 18 F] flubatine, which is successfully used for neuroimaging of alpha4beta2 nAChRs with PET. To assess the radiation risk by this new radiotracer, biodistribution, organ doses (OD) and the effective dose (ED) were investigated in a preclinical trials using piglets. Method: whole body dosimetry of (+)-[ 18 F] flubatine was performed in 3 female piglets (age: 43 ± 1.2 days, weight: 14 ± 1.0 kg). The animals were narcotized using 20 mg/kg Ketamine, 2 mg/kg Azaperone; 1.5% Isoflurane in 70% N 2 O/30% O 2 and sequentially PET-imaged up to 5 hours post i.v. injection of 183.5 ± 9.0 MBq on a SIEMENS Biograph16 PET/CT-system on 7 bed positions (BP) per frame, 1.5 to 6 min/BP, CT-attenuation correction (AC) and iterative reconstruction. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/g, and %ID/organ). Time- and mass-scales were adapted to the human order of magnitude. The ODs were calculated using the adult male model with OLINDA. The ED was calculated using tissue weighting factors as published in the ICRP103. Results: The highest OD was received by the urinary bladder (71.7 ± 26.3 μSv/MBq), the kidneys (45.1 ± 6.5 μSv/MBq) and the brain (32.3 ± 3.24 μSv/MBq). The highest contribution to the ED was by the urinary bladder (2.9 ± 1.1 μSv/MBq), the lungs (1.7 ± 0.02 μSv/MBq) and the red marrow (1.4 ± 0.1μSv/MBq). According to this data, the ED to humans is 14.3 ± 0.3 μSv/MBq. Conclusion: considering 40% underestimation of the ED to humans by preclinical dosimetry [1] the expected ED to humans after 300 MBq i.v. is 7.2 mSv, which is about the ED by (-)-[ 18 F]flubatine (6.8 mSv/300 MBq) and well within the range of what other 18 F-labeled compounds cause to humans. This risk assessment encourages to transfer (+)-[F 18 ] flubatine from preclinical to clinical study phases and to further develop

Flight Test of the F/A-18 Active Aeroelastic Wing Airplane

Science.gov (United States)

Voracek, David

2007-01-01

A viewgraph presentation of flight tests performed on the F/A active aeroelastic wing airplane is shown. The topics include: 1) F/A-18 AAW Airplane; 2) F/A-18 AAW Control Surfaces; 3) Flight Test Background; 4) Roll Control Effectiveness Regions; 5) AAW Design Test Points; 6) AAW Phase I Test Maneuvers; 7) OBES Pitch Doublets; 8) OBES Roll Doublets; 9) AAW Aileron Flexibility; 10) Phase I - Lessons Learned; 11) Control Law Development and Verification & Validation Testing; 12) AAW Phase II RFCS Envelopes; 13) AAW 1-g Phase II Flight Test; 14) Region I - Subsonic 1-g Rolls; 15) Region I - Subsonic 1-g 360 Roll; 16) Region II - Supersonic 1-g Rolls; 17) Region II - Supersonic 1-g 360 Roll; 18) Region III - Subsonic 1-g Rolls; 19) Roll Axis HOS/LOS Comparison Region II - Supersonic (open-loop); 20) Roll Axis HOS/LOS Comparison Region II - Supersonic (closed-loop); 21) AAW Phase II Elevated-g Flight Test; 22) Region I - Subsonic 4-g RPO; and 23) Phase II - Lessons Learned

Rotation and chromospheric emission among F, G, and K dwarfs of the Pleiades

Science.gov (United States)

Soderblom, David R.; Stauffer, John R.; Hudon, J. D.; Jones, Burton F.

1993-01-01

High-resolution echelle spectra of more than 100 F, G, and K dwarfs in the Pleiades are reported. Chromospheric activity in these stars is measured via comparisons of the profiles of H-alpha and the Ca II IR triplet to chromospherically inactive field stars. Consistent dereddened colors are determined from the available photometry and temperatures are derived. Most G and K dwarfs in the Pleiades rotate slowly, but about 20 percent of the stars are ultrafast rotators (UFRs). That fraction of UFRs is independent of color, and the highest rotation rates are found among the K dwarfs. The Pleiades exhibit a broad range in the strength of chromospheric emission at any one color. Most G and K dwarfs in the Pleiades show H-alpha and the IR triple in absorption, with filling in of the line cores.

{sup 18}F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with {sup 18}F-FDG and {sup 11}C-Methionine PET

Energy Technology Data Exchange (ETDEWEB)

Watabe, Tadashi [Osaka University Graduate School of Medicine, Department of Nuclear Medicine and Tracer Kinetics, Osaka (Japan); Osaka University Graduate School of Medicine, PET Molecular Imaging Center, Osaka (Japan); Ikeda, Hayato; Aoki, Masanao [Osaka University Graduate School of Medicine, Department of Nuclear Medicine and Tracer Kinetics, Osaka (Japan); Nagamori, Shushi; Wiriyasermkul, Pattama; Tanaka, Yoko; Hagiwara, Kohei; Kanai, Yoshikatsu [Osaka University Graduate School of Medicine, Department of Bio-system Pharmacology, Osaka (Japan); Naka, Sadahiro [Osaka University, Osaka University Graduate School of Medicine, Osaka University Hospital, Osaka (Japan); Kanai, Yasukazu [Osaka University Graduate School of Medicine, PET Molecular Imaging Center, Osaka (Japan); Osaka University Graduate School of Medicine, Department of Molecular Imaging in Medicine, Osaka (Japan); Shimosegawa, Eku [Osaka University Graduate School of Medicine, Department of Nuclear Medicine and Tracer Kinetics, Osaka (Japan); Osaka University Graduate School of Medicine, PET Molecular Imaging Center, Osaka (Japan); Osaka University, Osaka University Graduate School of Medicine, Osaka University Hospital, Osaka (Japan); Hatazawa, Jun [Osaka University Graduate School of Medicine, Department of Nuclear Medicine and Tracer Kinetics, Osaka (Japan); Osaka University Graduate School of Medicine, PET Molecular Imaging Center, Osaka (Japan); Osaka University, Immunology Frontier Research Center, Osaka (Japan)

2017-02-15

The purpose of this study was to evaluate the usefulness of L-4-borono-2-{sup 18}F-fluoro-phenylalanine ({sup 18}F-FBPA) as a tumor-specific probe, in comparison to {sup 18}F-FDG and {sup 11}C-methionine (Met), focusing on its transport selectivity by L-type amino acid transporter 1 (LAT1), which is highly upregulated in cancers. Cellular analyses of FBPA were performed to evaluate the transportability and K{sub m} value. PET studies were performed in rat xenograft models of C6 glioma (n = 12) and in rat models of turpentine oil-induced subcutaneous inflammation (n = 9). The kinetic parameters and uptake values on static PET images were compared using the one-tissue compartment model (K{sub 1}, k{sub 2}) and maximum standardized uptake value (SUVmax). The cellular analyses showed that FBPA had a lower affinity to a normal cell-type transporter LAT2 and induced less efflux through LAT2 among FBPA, Met, and BPA, while the efflux through LAT1 induced by FBPA was similar among the three compounds. The K{sub m} value of {sup 18}F-FBPA for LAT1 (196.8 ± 11.4 μM) was dramatically lower than that for LAT2 (2813.8 ± 574.5 μM), suggesting the higher selectivity of {sup 18}F-FBPA for LAT1. K{sub 1} and k{sub 2} values were significantly smaller in {sup 18}F-FBPA PET (K{sub 1} = 0.04 ± 0.01 ml/ccm/min and k{sub 2} = 0.07 ± 0.01 /min) as compared to {sup 11}C-Met PET (0.22 ± 0.09 and 0.52 ± 0.10, respectively) in inflammatory lesions. Static PET analysis based on the SUVmax showed significantly higher accumulation of {sup 18}F-FDG in the tumor and inflammatory lesions (7.2 ± 2.1 and 4.6 ± 0.63, respectively) as compared to both {sup 18}F-FBPA (3.2 ± 0.40 and 1.9 ± 0.19) and {sup 11}C-Met (3.4 ± 0.43 and 1.6 ± 0.11). No significant difference was observed between {sup 18}F-FBPA and {sup 11}C-Met in the static PET images. This study shows the utility of {sup 18}F-FBPA as a tumor-specific probe of LAT1 with low accumulation in the inflammatory lesions. (orig.)

14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid as a tracer of free fatty acid uptake and oxidation in myocardium and skeletal muscle

International Nuclear Information System (INIS)

Takala, Teemu O.; Nuutila, Pirjo; Pulkki, Kari; Oikonen, Vesa; Groenroos, Tove; Bergman, Joergen; Forsback, Sarita; Knuuti, Juhani; Savunen, Timo; Vaehaesilta, Tommi; Luotolahti, Matti; Kallajoki, Markku

2002-01-01

14(R,S)-[ 18 F]Fluoro-6-thia-heptadecanoic acid ([ 18 F]FTHA) is a long-chain fatty acid substrate for fatty acid metabolism. [ 18 F]FTHA has been used to study fatty acid metabolism in human heart and skeletal muscle. It has been suggested that the rate of radioactivity accumulation in the myocardium reflects the beta-oxidation rate of free fatty acids (FFAs). However, the net accumulation of FFAs in tissue always represents the sum of FFA oxidation and incorporation into triglycerides. The fraction of [ 18 F]FTHA entering directly into mitochondria for oxidation has not been previously measured. Eight anaesthetized pigs were studied with [ 18 F]FTHA and positron emission tomography (PET). Immediately after each PET experiment, tissue samples from myocardium and skeletal muscle were taken for the isolation of mitochondria and measurements of radioactivity accumulation, and for intracellular [ 18 F]FTHA metabolite analysis. Fractional [ 18 F]FTHA uptake rates were calculated both by graphical analysis of PET data and by measuring 18 F in the tissue samples. Fractional [ 18 F]FTHA uptake rates based on the analysis of tissue samples were 0.56±0.17 ml g -1 min -1 and 0.037±0.007 ml g -1 min -1 for myocardium and skeletal muscle (mean ± SD), respectively. The myocardial results obtained from the PET data (0.50±0.11 ml g -1 min -1 ) were similar to the values obtained from the tissue samples (r=0.94, P=0.002). We also found that 89%±23% (mean±SD, n=7) of the 18 F entered mitochondria in myocardium, as compared with only 36%±15% (mean±SD, n=7) in skeletal muscle. Intracellular [ 18 F]FTHA metabolite analysis showed that a major part of [ 18 F]FTHA is metabolized in the mitochondria in the heart. Our data suggest that 89% of [ 18 F]FTHA taken up by the heart enters mitochondria. This supports the hypothesis that [ 18 F]FTHA traces FFA beta-oxidation in the heart. In contrast to this, only 36% of [ 18 F]FTHA accumulated in skeletal muscle appears to directly enter

Synthesis of 4-([{sup 18}F]fluoromethyl)-2-chlorophenylisothiocyanate: a novel bifunctional {sup 18}F-labelling agent

Energy Technology Data Exchange (ETDEWEB)

Wuest, F.; Mueller, M.; Bergmann, R. [Inst. fuer Bioanorganische und Radiopharmazeutische Chemie, FZ-Rossendorf e.V., Dresden (Germany)

2004-07-01

The one-step radiosynthesis of 4-([{sup 18}F]fluoromethyl)-2-chlorophenylisothiocyanate {sup 18}F-7 as a novel bifunctional {sup 18}F-labelling agent is described. Optimised reaction conditions in a remotely controlled synthesis module gave isothiocyanate {sup 18}F-7 in radiochemical yields of 45% (decay-corrected) within 40 min and high radiochemical purity of > 95% after solid-phase-extraction. Coupling of compound {sup 18}F-7 with the primary amine benzylamine as a model reaction afforded the corresponding ((4-[{sup 18}F]fluoromethyl)-2-chloro-phenyl)-benzyl thiourea {sup 18}F-8 in a high radiochemical yield of > 90%. Stability studies of thiourea {sup 18}F-8 in terms of radiodefluorination showed appreciable buffer stability at pH 7.4, whereas significant radiodefluorination was observed when {sup 18}F-8 was incubated in buffers at pH 3.6 and pH 9.4. Preliminary dynamic PET studies with thiourea {sup 18}F-8 in male Wistar rats showed high bone accumulation, indicative of high in vivo radiodefluorination. (orig.)

Quantitative analysis and comparison study of [18F]AlF-NOTA-PRGD2, [18F]FPPRGD2 and [68Ga]Ga-NOTA-PRGD2 using a reference tissue model.

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Ning Guo

Full Text Available With favorable pharmacokinetics and binding affinity for α(vβ(3 integrin, (18F-labeled dimeric cyclic RGD peptide ([(18F]FPPRGD2 has been intensively used as a PET imaging probe for lesion detection and therapy response monitoring. A recently introduced kit formulation method, which uses an (18F-fluoride-aluminum complex labeled RGD tracer ([(18F]AlF-NOTA-PRGD2, provides a strategy for simplifying the labeling procedure to facilitate clinical translation. Meanwhile, an easy-to-prepare (68Ga-labeled NOTA-PRGD2 has also been reported to have promising properties for imaging integrin α(vβ(3. The purpose of this study is to quantitatively compare the pharmacokinetic parameters of [(18F]FPPRGD2, [(18F]AlF-NOTA-PRGD2, and [(68Ga]Ga-NOTA-PRGD2. U87MG tumor-bearing mice underwent 60-min dynamic PET scans following the injection of three tracers. Kinetic parameters were calculated using Logan graphical analysis with reference tissue. Parametric maps were generated using voxel-level modeling. All three compounds showed high binding potential (Bp(ND = k(3/k(4 in tumor voxels. [(18F]AlF-NOTA-PRGD2 showed comparable Bp(ND value (3.75±0.65 with those of [(18F]FPPRGD2 (3.39±0.84 and [(68Ga]Ga-NOTA-PRGD2 (3.09±0.21 (p>0.05. Little difference was found in volume of distribution (V(T among these three RGD tracers in tumor, liver and muscle. Parametric maps showed similar kinetic parameters for all three tracers. We also demonstrated that the impact of non-specific binding could be eliminated in the kinetic analysis. Consequently, kinetic parameter estimation showed more comparable results among groups than static image analysis. In conclusion, [(18F]AlF-NOTA-PRGD2 and [(68Ga]Ga-NOTA-PRGD2 have comparable pharmacokinetics and quantitative parameters compared to those of [(18F]FPPRGD2. Despite the apparent difference in tumor uptake (%ID/g determined from static images and clearance pattern, the actual specific binding component extrapolated from kinetic

Synthesis and evaluation of 7α-(3-[18F]fluoropropyl) estradiol

International Nuclear Information System (INIS)

Okamoto, Mayumi; Naka, Kyosuke; Kitagawa, Yuya; Ishiwata, Kiichi; Yoshimoto, Mitsuyoshi; Shimizu, Isao; Toyohara, Jun

2015-01-01

Introduction: Several lines of evidence suggest that C-7α-substituted estradiol derivatives are well tolerated by estrogen receptor (ER). In line with this hypothesis, we are interested in the design and synthesis of C-7α-substituted estrogens as molecular probes to visualize ER function. Methods: We have synthesized 7α-(3-[ 18 F]fluoropropyl) estradiol (C3-7α-[ 18 F]FES) as a potential radiopharmaceutical for ER imaging by positron emission tomography (PET). In vitro receptor binding and in vivo biodistribution and blocking studies in mature female mice, and in vivo metabolite analysis were carried out. Furthermore, in vivo ER-selective uptake was confirmed using ER-positive T-47D and ER-negative MDA-MB-231 tumor-bearing mice. We also compared the in vivo biodistribution of C3-7α-[ 18 F]FES with 16α-[ 18 F]FES. Results: C3-7α-[ 18 F]FES was produced in moderate yields (30.7% ± 15.1%, decay corrected) with specific activity of 32.0 ± 18.1 GBq/μmol (EOS). The in vitro binding affinity of C3-7α-FES to the ERα isoform was sufficient and equivalent to that of estradiol. C3-7α-[ 18 F]FES showed selective uptake in ER-rich tissues, such as the uterus (4.7%ID/g ± 1.2%ID/g at 15 minutes) and ovary (4.0%ID/g ± 1.0%ID/g at 5 minutes). The tissue time activity curves of these organs showed reversible kinetics, indicating suitability for quantitative analysis. The highest contrast was obtained at 120 minutes after injection of C3-7α-[ 18 F]FES in the uterus (uterus/blood = 18, uterus/muscle = 17.3) and ovary (ovary/blood = 6.3, ovary/muscle = 6.0). However, the level of selective uptake of C3-7α-[ 18 F]FES was significantly lower than that of 16α-[ 18 F]FES. Most radioactivity in the uterus was detected in unchanged form, although peripherally C3-7α-[ 18 F]FES was rapidly degraded to hydrophilic metabolites. In accordance with this peripheral metabolism, gradual increases in bone radioactivity were observed, indicating defluorination. Coinjection with

"1"8F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with "1"8F-FDG and "1"1C-Methionine PET

International Nuclear Information System (INIS)

Watabe, Tadashi; Ikeda, Hayato; Aoki, Masanao; Nagamori, Shushi; Wiriyasermkul, Pattama; Tanaka, Yoko; Hagiwara, Kohei; Kanai, Yoshikatsu; Naka, Sadahiro; Kanai, Yasukazu; Shimosegawa, Eku; Hatazawa, Jun

2017-01-01

The purpose of this study was to evaluate the usefulness of L-4-borono-2-"1"8F-fluoro-phenylalanine ("1"8F-FBPA) as a tumor-specific probe, in comparison to "1"8F-FDG and "1"1C-methionine (Met), focusing on its transport selectivity by L-type amino acid transporter 1 (LAT1), which is highly upregulated in cancers. Cellular analyses of FBPA were performed to evaluate the transportability and K_m value. PET studies were performed in rat xenograft models of C6 glioma (n = 12) and in rat models of turpentine oil-induced subcutaneous inflammation (n = 9). The kinetic parameters and uptake values on static PET images were compared using the one-tissue compartment model (K_1, k_2) and maximum standardized uptake value (SUVmax). The cellular analyses showed that FBPA had a lower affinity to a normal cell-type transporter LAT2 and induced less efflux through LAT2 among FBPA, Met, and BPA, while the efflux through LAT1 induced by FBPA was similar among the three compounds. The K_m value of "1"8F-FBPA for LAT1 (196.8 ± 11.4 μM) was dramatically lower than that for LAT2 (2813.8 ± 574.5 μM), suggesting the higher selectivity of "1"8F-FBPA for LAT1. K_1 and k_2 values were significantly smaller in "1"8F-FBPA PET (K_1 = 0.04 ± 0.01 ml/ccm/min and k_2 = 0.07 ± 0.01 /min) as compared to "1"1C-Met PET (0.22 ± 0.09 and 0.52 ± 0.10, respectively) in inflammatory lesions. Static PET analysis based on the SUVmax showed significantly higher accumulation of "1"8F-FDG in the tumor and inflammatory lesions (7.2 ± 2.1 and 4.6 ± 0.63, respectively) as compared to both "1"8F-FBPA (3.2 ± 0.40 and 1.9 ± 0.19) and "1"1C-Met (3.4 ± 0.43 and 1.6 ± 0.11). No significant difference was observed between "1"8F-FBPA and "1"1C-Met in the static PET images. This study shows the utility of "1"8F-FBPA as a tumor-specific probe of LAT1 with low accumulation in the inflammatory lesions. (orig.)

Stress corrosion cracking (Standard Astm G 30-90) in stainless steel 08X18H10T of swimming-pool that contain nuclear fuel in reactors V.V.E.R.-440

International Nuclear Information System (INIS)

Zamora R, L.; Herrera, V.

1998-01-01

The standard recommended practice for making and using 'U' bend stress corrosion test specimens; Designation G30-90 has been used as a laboratory tool to study the susceptibility of austenitic stainless steels and the other materials of test of intergranular stress corrosion cracking (IGSCC). The experiment has been development in a similar conditions of the chemical regime, the swimming-pool that containing nuclear fuel in borated water reactors VVER-440 in general this cladding by two films, one of carbon steel (04T26) and other with austenitic stainless steel 08X18HT (similar type 321) stabilized with titanium, the thickness of filler metals was to 4 to 8 mm. The specimens was prepare one plate with this characteristics, the welding was put in the part central with the following measurements of 160x15x5 mm. The specimens strips bent approximately 180 degrees around radius of curvature of R=14.5 mm and ε 1 = 17.2% and maintained in this plastically deformed condition during the test. And then preparing metallographically and exposure in environment of 12 and 40 gr./l of H 3 BO 3 70 Centigrade with or noting contaminants of NaCl. The results showed the initial cracks. (Author)

Measurement of high temperature elastic moduli of an 18Cr-9Ni-2.95 Cu-0.58 Nb-0.1C (Wt %) austenitic stainless steel

Science.gov (United States)

Tripathy, Haraprasanna; Hajra, Raj Narayan; Sudha, C.; Raju, S.; Saibaba, Saroja

2018-04-01

The Young's modulus (E) and Shear modulus (G) of an indigenously developed 18Cr-9Ni-0.1C-2.95 Cu-0.58Nb (wt %) austenitic stainless steel has been evaluated in the temperature range 298 K to 1273 K (25 °C to 1000 °C), using Impulse excitation technique (IET). The Bulk modulus (K) and the poison's ratio have been estimated from the measured values of E and G. It is observed that the elastic constants (E, G and K) are found to decrease in a nonlinear fashion with increase in temperature. The Cu precipitation is found to influence the elastic moduli of the steel in the cooling cycle. The observed elastic moduli are fitted to 3rd order polynomial equations in order to describe the temperature dependence of E, G, K moduli in the temperature range 298-1273 K (25 °C to 1000 °C). The room temperature values of E,G and K moduli is found to be 207, 82 and 145 GPa respectively for the present steel.

Automated radiosynthesis of no-carrier-added 4-[18F]fluoroiodobenzene: a versatile building block in 18F radiochemistry.

Science.gov (United States)

Way, Jenilee Dawn; Wuest, Frank

2014-02-01

4-[18F]Fluoroiodobenzene ([18F]FIB) is a versatile building block in 18F radiochemistry used in various transition metal-mediated C-C and C-N cross-coupling reactions and [18F]fluoroarylation reactions. Various synthesis routes have been described for the preparation of [18F]FIB. However, to date, no automated synthesis of [18F]FIB has been reported to allow access to larger amounts of [18F]FIB in high radiochemical and chemical purity. Herein, we describe an automated synthesis of no-carrier-added [18F]FIB on a GE TRACERlab™ FX automated synthesis unit starting from commercially available(4-iodophenyl)diphenylsulfonium triflate as the labelling precursor. [18F]FIB was prepared in high radiochemical yields of 89 ± 10% (decay-corrected, n = 7) within 60 min, including HPLC purification. The radiochemical purity exceeded 95%, and specific activity was greater than 40 GBq/μmol. Typically, from an experiment, 6.4 GBq of [18F]FIB could be obtained starting from 10.4 GBq of [18F]fluoride.

Fluorinated benzamide neuroleptics--III. Development of (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[{sup 18}F]fluoropropyl)-2,3- dimethoxybenzamide as an improved dopamine D-2 receptor tracer

Energy Technology Data Exchange (ETDEWEB)

Mukherjee, Jogeshwar; Zhiying, Yang; Das, Malay K; Brown, Terry

1995-04-01

We have prepared five new analogs (n-propyl, iso-propyl, allyl, n-butyl, and iso-butyl) of the dopamine D-2 receptor antagonist, FPMB which result from modifications of the ethyl group at the pyrrolidine nitrogen in FPMB. As expected, all new derivatives showed higher apparent lipophilicity (log k{sub w}), with iso-butyl being the most lipophilic (log k{sub w} = 2.52), followed by the allyl derivative (log k{sub w} = 2.43). The allyl group showed the largest increase in affinity (from 0.26 nM for the ethyl substituent to 0.03 nM for the allyl substituent, almost 10-fold), followed by the n-propyl substituent which showed approximately five-fold better affinity than did the ethyl substituent. Radiosynthesis of S-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[{sup 18}F]fluoropropyl)-2,3-dimethoxybenzamide ([{sup 18}F]fallypride) was carried out by nucleophilic substitution reaction of (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-tosyloxypropyl)-2,3- dimethoxybenzamide with no carrier added {sup 18}F{sup -}. [{sup 18}F]Fallypride was obtained in approximately 20-40% yields (EOS/EOB, decay corrected) in specific activities of 900-1700 Ci/mmol after reverse phase HPLC purification in 60 min from EOB. High striatal uptake (upto 2.5% injected dose/g) of [{sup 18}F]fallypride in rats was observed with striatal/cerebellar ratios of 17, 42, 63 and 122 at 30, 60, 90 and 120 min post-injection, respectively. PET experiments with [{sup 18}F]fallypride in a cebus monkey showed a brain uptake of 0.10% injected dose/cc. In rhesus monkeys [{sup 18}F]fallypride showed rapid specific uptake in the striata (0.04-0.06% injected dose/cc) with striata/cerebellum ratios of approx. 3.0 at 14 min, 5.0 at 35 min and 8 at 70 min post-injection. Specifically bound [{sup 18}F]fallypride was displaced with haloperidol (1 mg/kg) with a half-life of 18 min in the rhesus monkey.

Treatment response evaluation with 18F-FDG PET/CT and 18F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation.

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Sachpekidis, Christos; Hillengass, J; Goldschmidt, H; Wagner, B; Haberkorn, U; Kopka, K; Dimitrakopoulou-Strauss, A

2017-01-01

The aim of this study was to assess the combined use of the radiotracers 18 F-FDG and 18 F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with 18 F-FDG and 18 F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, 18 F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, 18 F-FDG PET/CT-based treatment response revealed CR in 14 patients ( 18 F-FDG PET/CT CR), PR in 11 patients ( 18 F-FDG PET/CT PR) and progressive disease in four patients ( 18 F-FDG PET/CT PD). In terms of 18 F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, 18 F-NaF PET/CT depicted 56 of the 129 18 F-FDG positive lesions (43 %). Follow-up 18 F-NaF PET/CT showed persistence of 81.5 % of the baseline 18 F-NaF positive MM lesions after treatment, despite the fact that 64

Effect of operational conditions of electroerosion machining on the surface microgeometry parameters of steels and alloys

International Nuclear Information System (INIS)

Foteev, N.K.

1976-01-01

Studies the influence of pulse duration and a series of operating conditions of a ShGI-40-440 spark-machining generator on changes in the basic surface microgeometry characteristics of components of stainless steel 1Kh18N10T, steel St 45 and hard alloy T14K8. The microgeometry characteristics of spark-machined surfaces differ significantly from the corresponding characteristics of surfaces machined by cutting and vibro-rolling

Preparation and evaluation of ethyl [18F]fluoroacetate as a proradiotracer of [18F]fluoroacetate for the measurement of glial metabolism by PET

International Nuclear Information System (INIS)

Mori, Tetsuya; Sun, Li-Quan; Kobayashi, Masato; Kiyono, Yasushi; Okazawa, Hidehiko; Furukawa, Takako; Kawashima, Hidekazu; Welch, Michael J.; Fujibayashi, Yasuhisa

2009-01-01

Introduction: Changes in glial metabolism in brain ischemia, Alzheimer's disease, depression, schizophrenia, epilepsy and manganese neurotoxicity have been reported in recent studies. Therefore, it is very important to measure glial metabolism in vivo for the elucidation and diagnosis of these diseases. Radiolabeled acetate is a good candidate for this purpose, but acetate has little uptake in the brain due to its low lipophilicity. We have designed a new proradiotracer, ethyl [ 18 F]fluoroacetate ([ 18 F]EFA), which is [ 18 F]fluoroacetate ([ 18 F]FA) esterified with ethanol, to increase the lipophilicity of fluoroacetate (FA), allowing the measurement of glial metabolism. Methods: The synthesis of [ 18 F]EFA was achieved using ethyl O-mesyl-glycolate as precursor. The blood-brain barrier permeability of ethyl [1- 14 C]fluoroacetate ([ 14 C]EFA) was estimated by a brain uptake index (BUI) method. Hydrolysis of [ 14 C]EFA in the brain was calculated by the fraction of radioactivity in lipophilic and water fractions of homogenized brain. Using the plasma of five animal species, the stability of [ 14 C]EFA was measured. Biodistribution studies of [ 18 F]EFA in ddY mice were carried out and compared with [ 18 F]FA. Positron emission tomography (PET) scanning using common marmosets was performed for 90 min postadministration. At 60 min postinjection of [ 18 F]EFA, metabolite studies were performed. Organs were dissected from the marmosets, and extracted metabolites were analyzed with a thin-layer chromatography method. Results: The synthesis of [ 18 F]EFA was accomplished in a short time (29 min) and with a reproducible radiochemical yield of 28.6±3.6% (decay corrected) and a high radiochemical purity of more than 95%. In the brain permeability study, the BUI of [ 14 C]EFA was 3.8 times higher than that of sodium [1- 14 C]fluoroacetate. [ 14 C]EFA was hydrolyzed rapidly in rat brains. In stability studies using the plasma of five animal species, [ 14 C]EFA was stable

In vivo evaluation in rats of [18F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine as a potential radiotracer for PET assessment of CNS sigma-1 receptors

International Nuclear Information System (INIS)

Waterhouse, Rikki N.; Chang, Raymond C.; Zhao, Jun; Carambot, Patty E.

2006-01-01

Introduction: Sigma-1 receptors are expressed throughout the mammalian central nervous system (CNS) and are implicated in several psychiatric disorders, including schizophrenia and depression. We have recently evaluated the high-affinity (K D =0.5±0.2 nM, log P=2.9) sigma-1 receptor radiotracer [ 18 F]1-(3-fluoropropyl)-4-(4-cyanophenoxymethyl)piperidine, [ 18 F]FPS, in humans. In contrast to appropriate kinetics exhibited in baboon brain, in the human CNS, [ 18 F]FPS does not reach pseudoequilibrium by 4 h, supporting the development of a lower-affinity tracer [Waterhouse RN, Nobler MS, Chang RC, Zhou Y, Morales O, Kuwabara H, et al. First evaluation of the sigma-1 receptor radioligand [ 18 F]1-3-fluoropropyl-4-((4-cyanophenoxy)-methyl)piperidine ([ 18 F]FPS) in healthy humans. Neuroreceptor Mapping 2004, July 15-18th, Vancouver, BC Canada 2004]. We describe herein the in vivo evaluation in rats of [ 18 F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine ([ 18 F]SFE) (K D =5 nM, log P=2.4), a structurally similar, lower-affinity sigma-1 receptor radioligand. Methods: [ 18 F]SFE was synthesized (n=4) as previously described in good yield (54±6% EOB), high specific activity (2.1±0.6 Ci/μmol EOS) and radiochemical purity (98±1%) and evaluated in awake adult male rats. Results: Similar to [ 18 F]FPS, regional brain radioactivity concentrations [percentage of injected dose per gram of tissue (%ID/g), 15 min] for [ 18 F]SFE were highest in occipital cortex (1.86±0.06 %ID/g) and frontal cortex (1.76±0.38 %ID/g), and lowest in the hippocampus (1.01±0.02%ID/g). Unlike [ 18 F]FPS, [ 18 F]SFE cleared from the brain with ∼40% reduction in peak activity over a 90-min period. Metabolite analysis (1 h) revealed that [ 18 F]SFE was largely intact in the brain. Blocking studies showed a large degree (>80%) of saturable binding for [ 18 F]SFE in discrete brain regions. Conclusions: We conclude that [ 18 F]SFE exhibits excellent characteristics in vivo and may provide

14(R,S)-[{sup 18}F]Fluoro-6-thia-heptadecanoic acid as a tracer of free fatty acid uptake and oxidation in myocardium and skeletal muscle

Energy Technology Data Exchange (ETDEWEB)

Takala, Teemu O.; Nuutila, Pirjo [Turku PET Centre, Turku University Central Hospital, PO Box 52, 20521 Turku (Finland); Department of Medicine, University of Turku (Finland); Pulkki, Kari [Department of Clinical Chemistry, University of Turku (Finland); Oikonen, Vesa; Groenroos, Tove; Bergman, Joergen; Forsback, Sarita; Knuuti, Juhani [Turku PET Centre, Turku University Central Hospital, PO Box 52, 20521 Turku (Finland); Savunen, Timo; Vaehaesilta, Tommi [Department of Surgery, University of Turku (Finland); Luotolahti, Matti [Department of Clinical Physiology, University of Turku (Finland); Kallajoki, Markku [Department of Pathology, University of Turku (Finland)

2002-12-01

14(R,S)-[{sup 18}F]Fluoro-6-thia-heptadecanoic acid ([{sup 18}F]FTHA) is a long-chain fatty acid substrate for fatty acid metabolism. [{sup 18}F]FTHA has been used to study fatty acid metabolism in human heart and skeletal muscle. It has been suggested that the rate of radioactivity accumulation in the myocardium reflects the beta-oxidation rate of free fatty acids (FFAs). However, the net accumulation of FFAs in tissue always represents the sum of FFA oxidation and incorporation into triglycerides. The fraction of [{sup 18}F]FTHA entering directly into mitochondria for oxidation has not been previously measured. Eight anaesthetized pigs were studied with [{sup 18}F]FTHA and positron emission tomography (PET). Immediately after each PET experiment, tissue samples from myocardium and skeletal muscle were taken for the isolation of mitochondria and measurements of radioactivity accumulation, and for intracellular [{sup 18}F]FTHA metabolite analysis. Fractional [{sup 18}F]FTHA uptake rates were calculated both by graphical analysis of PET data and by measuring {sup 18}F in the tissue samples. Fractional [{sup 18}F]FTHA uptake rates based on the analysis of tissue samples were 0.56{+-}0.17 ml g{sup -1} min{sup -1} and 0.037{+-}0.007 ml g{sup -1} min{sup -1} for myocardium and skeletal muscle (mean {+-} SD), respectively. The myocardial results obtained from the PET data (0.50{+-}0.11 ml g{sup -1} min{sup -1}) were similar to the values obtained from the tissue samples (r=0.94, P=0.002). We also found that 89%{+-}23% (mean{+-}SD, n=7) of the {sup 18}F entered mitochondria in myocardium, as compared with only 36%{+-}15% (mean{+-}SD, n=7) in skeletal muscle. Intracellular [{sup 18}F]FTHA metabolite analysis showed that a major part of [{sup 18}F]FTHA is metabolized in the mitochondria in the heart. Our data suggest that 89% of [{sup 18}F]FTHA taken up by the heart enters mitochondria. This supports the hypothesis that [{sup 18}F]FTHA traces FFA beta-oxidation in the heart

18F-radiolabeled analogs of exendin-4 for PET imaging of GLP-1 in insulinoma

International Nuclear Information System (INIS)

Kiesewetter, Dale O.; Ma, Ying; Niu, Gang; Quan, Qimeng; Guo, Ning; Chen, Xiaoyuan; Gao, Haokao

2012-01-01

Glucagon-like peptide type 1 (GLP-1) is an incretin peptide that augments glucose-stimulated insulin release following oral consumption of nutrients. Its message is transmitted via a G protein-coupled receptor called GLP-1R, which is colocalized with pancreatic β-cells. The GLP-1 system is responsible for enhancing insulin release, inhibiting glucagon production, inhibiting hepatic gluconeogenesis, inhibiting gastric mobility, and suppression of appetite. The abundance of GLP-1R in pancreatic β-cells in insulinoma, a cancer of the pancreas, and the activity of GLP-1 in the cardiovascular system have made GLP-1R a target for molecular imaging. We prepared 18 F radioligands for GLP-1R by the reaction of [ 18 F]FBEM, a maleimide prosthetic group, with [Cys 0 ] and [Cys 40 ] analogs of exendin-4. The binding affinity, cellular uptake and internalization, in vitro stability, and uptake and specificity of uptake of the resulting compounds were determined in an INS-1 xenograft model in nude mice. The [ 18 F]FBEM-[Cys x ]-exendin-4 analogs were obtained in good yield (34.3 ± 3.4%, n = 11), based on the starting compound [ 18 F]FBEM, and had a specific activity of 45.51 ± 16.28 GBq/μmol (1.23 ± 0.44 Ci/μmol, n = 7) at the end of synthesis. The C-terminal isomer, [ 18 F]FBEM-[Cys 40 ]-exendin-4, had higher affinity for INS-1 tumor cells (IC 50 1.11 ± 0.057 nM) and higher tumor uptake (25.25 ± 3.39 %ID/g at 1 h) than the N-terminal isomer, [ 18 F]FBEM-[Cys 0 ]-exendin-4 (IC 50 2.99 ± 0.06 nM, uptake 7.20 ± 1.26 %ID/g at 1 h). Uptake of both isomers into INS-1 tumor, pancreas, stomach, and lung could be blocked by preinjection of nonradiolabeled [Cys x ]-exendin-4 (p 18 F]FBEM-[Cys 40 ]-exendin-4 and [ 18 F]FBEM-[Cys 0 ]-exendin-4 have high affinity for GLP-1R and display similar in vitro cell internalization. The higher uptake into INS-1 xenograft tumors exhibited by [ 18 F]FBEM-[Cys 40 ]-exendin-4 suggests that this compound would be the better tracer for imaging

IgG4-Related Disease Simulating Carcinoma Colon With Diffuse Peritoneal Carcinomatosis on 18F-FDG PET/CT.

Science.gov (United States)

Vadi, Shelvin Kumar; Parihar, Ashwin Singh; Kumar, Rajender; Singh, Harmandeep; Mittal, Bhagwant Rai; Bal, Amanjit; Sinha, Saroj Kumar

2018-05-14

IgG4-related disease (IgG4-RD) continues to be a diagnostic challenge and a great mimicker of malignancies. We report here a case of young man who presented with subacute intestinal obstruction with initial imaging and clinical features suggestive of carcinoma colon. 18F-FDG PET/CT showed diffuse peritoneal carcinomatosis pattern typically seen with abdominal malignancies. However, the histopathology and the raised IgG4 levels diagnosed it to be IgG4-RD. Although 18F-FDG PET/CT has typical patterns corresponding to the multisystemic involvement of IgG4-RD, the index case did not show any such findings.

Comparison of low-cycle fatigue data of 2 1/4%CrMo steels

International Nuclear Information System (INIS)

Sanderson, S.J.; Petrequin, P.; Nieuwland, H.C.D.

Data files have been produced on international strain-controlled fatigue information available for 2 1/4%CrMo steels; data assessment from these files is treated in three categories viz: annealed and isothermally annealed 2 1/4%Cr1%Mo steel; normalised and tempered and quenched and tempered 2 1/4%Cr1%Mo steel; and 2 1/4%CrMo variants. The available data have been considered generally in terms of total strain range vs. cycles to failure (Nsub(f)), tensile stress at Nsub(f)/2 vs. cycles to failure and time to failure vs. cycles to failure. Where possible the continuous cycling data have been statistically analysed in terms of the elastic and plastic strain components and cycles to failure to yield best-fit equations over defined temperature (T) regimes viz: T <= 427 deg. C, 427 deg. C < T <= 550 deg. C. and 550 deg. C < T <= 600 deg. C. The behaviour of the steels within the various classifications is discussed. (author)

Preliminary evaluation of 1′-[18F]fluoroethyl-β-D-lactose ([18F]FEL) for detection of pancreatic cancer in nude mouse orthotopic xenografts

International Nuclear Information System (INIS)

Arumugam, Thiruvengadam; Paolillo, Vincenzo; Young, Daniel; Wen, XiaoXia; Logsdon, Craig D.; De Palatis, Louis; Alauddin, Mian M.

2014-01-01

Introduction: Early detection of pancreatic cancer could save many thousands of lives. Non-invasive diagnostic imaging, including PET with [ 18 F]FDG, has inadequate resolution for detection of small (2–3 mm) pancreatic tumours. We demonstrated the efficacy of PET imaging with an 18 F-labelled lactose derivative, [ 18 F]FEDL, that targets HIP/PAP, a biomarker that is overexpressed in the peritumoural pancreas. We developed another analogue, 1-[ 18 F]fluoroethyl lactose ([ 18 F]FEL), which is simpler to synthesise, for the same application. We conducted a preliminary evaluation of the new probe and its efficacy in detecting orthotopic pancreatic carcinoma xenografts in mice. Methods: Xenografts were developed in nude mice by injecting L3.6pl/GL + pancreatic carcinoma cells into the pancreas of each mouse. Tumour growth was monitored by bioluminescence imaging (BLI); accuracy of BLI tumour size estimates was verified by MRI in two representative mice. When the tumour size reached approximately 2–3 mm, the animals were injected with [ 18 F]FEL (3.7 MBq) and underwent static PET/CT scans. Blood samples were collected at 2, 5, 10, 20 and 60 min after [ 18 F]FEL injection to track blood clearance. Following imaging, animals were sacrificed and their organs and tumours/pancreatic tissue were collected and counted on a gamma counter. Pancreas, including tumour, was frozen, sliced and used for autoradiography and immunohistochemical analysis of HIP/PAP expression. Results: Tumour growth was rapid, as observed by BLI and MRI. Blood clearance of [ 18 F]FEL was bi-exponential, with half-lives of approximately 3.5 min and 40 min. Mean accumulation of [ 18 F]FEL in the peritumoural pancreatic tissue was 1.29 ± 0.295 %ID/g, and that in the normal pancreas of control animals was 0.090 ± 0.101 %ID/g. [ 18 F]FEL was cleared predominantly by the kidneys. Comparative analysis of autoradiographic images and immunostaining results demonstrated a correlation between [ 18 F

Staging and Functional Characterization of Pheochromocytoma and Paraganglioma by 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography

Science.gov (United States)

Timmers, Henri J. L. M.; Chen, Clara C.; Carrasquillo, Jorge A.; Whatley, Millie; Ling, Alexander; Eisenhofer, Graeme; King, Kathryn S.; Rao, Jyotsna U.; Wesley, Robert A.; Adams, Karen T.

2012-01-01

Background Pheochromocytomas and paragangliomas (PPGLs) are rare tumors of the adrenal medulla and extra-adrenal sympathetic chromaffin tissues; their anatomical and functional imaging are critical to guiding treatment decisions. This study aimed to compare the sensitivity and specificity of 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) for tumor localization and staging of PPGLs with that of conventional imaging by [123I]-metaiodobenzylguanidine single photon emission CT (123I-MIBG SPECT), CT, and magnetic resonance imaging (MRI). Methods A total of 216 patients (106 men, 110 women, aged 45.2 ± 14.9 years) with suspected PPGL underwent CT or MRI, 18F-FDG PET/CT, and 123I-MIBG SPECT/CT. Sensitivity and specificity were measured as endpoints and compared by the McNemar test, using two-sided P values only. Results Sixty (28%) of patients had nonmetastatic PPGL, 95 (44%) had metastatic PPGL, and 61 (28%) were PPGL negative. For nonmetastatic tumors, the sensitivity of 18F-FDG was similar to that of 123I-MIBG but less than that of CT/MRI (sensitivity of 18F-FDG = 76.8%; of 123I-MIBG = 75.0%; of CT/MRI = 95.7%; 18F-FDG vs 123I-MIBG: difference = 1.8%, 95% confidence interval [CI] = −14.8% to 14.8%, P = .210; 18F-FDG vs CT/MRI: difference = 18.9%, 95% CI = 9.4% to 28.3%, P < .001). The specificity was 90.2% for 18F-FDG, 91.8% for 123I-MIBG, and 90.2% for CT/MRI. 18F-FDG uptake was higher in succinate dehydrogenase complex– and von Hippel–Lindau syndrome–related tumors than in multiple endocrine neoplasia type 2 (MEN2) related tumors. For metastases, sensitivity was greater for 18F-FDG and CT/MRI than for 123I-MIBG (sensitivity of 18F-FDG = 82.5%; of 123I-MIBG = 50.0%; of CT/MRI = 74.4%; 18F-FDG vs 123I-MIBG: difference = 32.5%, 95% CI = 22.3% to 42.5%, P < .001; CT/MRI vs 123I-MIBG: difference = 24.4%, 95% CI = 11.3% to 31.6%, P < .001). For bone metastases, 18F-FDG was more sensitive than CT/MRI (sensitivity of 18

Hydrogen behaviour in the aged low activation martensitic steel F82H for fusion reactor applications

International Nuclear Information System (INIS)

Benamati, G.

1997-10-01

A time dependent permeation method is used to measure the permeability, diffusivity and solubility of hydrogen in the low activation martensitic steel F82H aged for 2000 h under vacuum at 773 K. The measurements cover the temperature range from 373 to 723 K which includes the onset of hydrogen trapping effects on diffusivity and solubility. The results are interpreted using a trapping model. The number of trap sites and their average energies for hydrogen in the aged F82H steel are determined. These data are compared with those obtained for deuterium in F82H steel

Treatment response evaluation with {sup 18}F-FDG PET/CT and {sup 18}F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation

Energy Technology Data Exchange (ETDEWEB)

Sachpekidis, Christos [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Bern, Department of Nuclear Medicine, Inselspital, Bern University Hospital, Bern (Switzerland); Hillengass, J.; Wagner, B. [University Hospital Heidelberg, Department of Internal Medicine V, Heidelberg (Germany); Goldschmidt, H. [University Hospital Heidelberg, Department of Internal Medicine V, Heidelberg (Germany); National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg (Germany); Haberkorn, U. [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Kopka, K. [German Cancer Research Center (DKFZ), Department of Radiopharmaceutical Chemistry, Heidelberg (Germany); Dimitrakopoulou-Strauss, A. [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany)

2017-01-15

The aim of this study was to assess the combined use of the radiotracers {sup 18}F-FDG and {sup 18}F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with {sup 18}F-FDG and {sup 18}F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, {sup 18}F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, {sup 18}F-FDG PET/CT-based treatment response revealed CR in 14 patients ({sup 18}F-FDG PET/CT CR), PR in 11 patients ({sup 18}F-FDG PET/CT PR) and progressive disease in four patients ({sup 18}F-FDG PET/CT PD). In terms of {sup 18}F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, {sup 18}F-NaF PET/CT depicted 56 of the 129 {sup 18}F-FDG positive lesions (43 %). Follow-up {sup 18}F-NaF PET/CT showed persistence of 81.5 % of the baseline {sup 18}F-NaF

[{sup 18}F]DPA-714 PET imaging of translocator protein TSPO (18 kDa) in the normal and excitotoxically-lesioned nonhuman primate brain

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Lavisse, S.; Inoue, K.; Jan, C.; Petit, F.; Dauguet, J.; Guillermier, M.; Rbah-Vidal, L.; Van Camp, N.; Aron-Badin, R.; Hantraye, P. [CEA, I2BM, MIRCen, Fontenay-aux-Roses (France); CEA, CNRS, URA2210, Fontenay-aux-Roses (France); Peyronneau, M.A.; Goutal, S.; Dolle, F. [CEA, I2BM, Service Hospitalier Frederic Joliot, Orsay (France); Remy, P. [CEA, I2BM, MIRCen, Fontenay-aux-Roses (France); CEA, CNRS, URA2210, Fontenay-aux-Roses (France); Service de Neurologie, CHU Henri Mondor, Creteil (France)

2014-12-09

We aimed to characterize pharmacologically the TSPO- radioligand [{sup 18}F]DPA-714 in the brain of healthy cynomolgus monkeys and evaluate the cellular origin of its binding in a model of neurodegeneration induced by intrastriatal injection of quinolinic acid (QA). [{sup 18}F]DPA-714 PET images were acquired before and at 2, 7, 14, 21, 49, 70, 91 days after putaminal lesioning. Blocking and displacement studies were carried out (PK11195). Different modelling approaches estimated rate constants and V{sub T} (total distribution volume) which was used to measure longitudinal changes in the lesioned putamen. Sections for immunohistochemical labelling were prepared at the same time-points to evaluate correlations between in vivo [{sup 18}F]DPA-714 binding and microglial/astrocytic activation. [{sup 18}F]DPA-714 showed a widespread distribution with a higher signal in the thalamus and occipital cortex and lower binding in the cerebellum. TSPO was expressed throughout the whole brain and about 73 % of [{sup 18}F]DPA-714 binding was specific for TSPO in vivo. The one-tissue compartment model (1-TCM) provided good and reproducible estimates of V{sub T} and rate constants, and V{sub T} values from the 1-TCM and the Logan approach were highly correlated (r {sup 2} = 0.85). QA lesioning induced an increase in V{sub T}, which was +17 %, +54 %, +157 % and +39 % higher than baseline on days 7, 14, 21 and 91 after QA injection, respectively. Immunohistochemistry revealed an early microglial and a delayed astrocytic activation after QA injection. [{sup 18}F]DPA-714 binding matched TSPO immunopositive areas and showed a stronger colocalization with CD68 microglia than with GFAP-activated astrocytes. [{sup 18}F]DPA-714 binds to TSPO with high specificity in the primate brain under normal conditions and in the QA model. This tracer provides a sensitive tool for assessing neuroinflammation in the human brain. (orig.)

{sup 18}F-radiolabeled analogs of exendin-4 for PET imaging of GLP-1 in insulinoma

Energy Technology Data Exchange (ETDEWEB)

Kiesewetter, Dale O.; Ma, Ying; Niu, Gang; Quan, Qimeng; Guo, Ning; Chen, Xiaoyuan [National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), Bethesda, MD (United States); Gao, Haokao [National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), Bethesda, MD (United States); Fourth Military Medical University, Department of Cardiology, Xijing Hospital, Xi' an (China)

2012-03-15

Glucagon-like peptide type 1 (GLP-1) is an incretin peptide that augments glucose-stimulated insulin release following oral consumption of nutrients. Its message is transmitted via a G protein-coupled receptor called GLP-1R, which is colocalized with pancreatic {beta}-cells. The GLP-1 system is responsible for enhancing insulin release, inhibiting glucagon production, inhibiting hepatic gluconeogenesis, inhibiting gastric mobility, and suppression of appetite. The abundance of GLP-1R in pancreatic {beta}-cells in insulinoma, a cancer of the pancreas, and the activity of GLP-1 in the cardiovascular system have made GLP-1R a target for molecular imaging. We prepared {sup 18}F radioligands for GLP-1R by the reaction of [{sup 18}F]FBEM, a maleimide prosthetic group, with [Cys{sup 0}] and [Cys{sup 40}] analogs of exendin-4. The binding affinity, cellular uptake and internalization, in vitro stability, and uptake and specificity of uptake of the resulting compounds were determined in an INS-1 xenograft model in nude mice. The [{sup 18}F]FBEM-[Cys{sup x}]-exendin-4 analogs were obtained in good yield (34.3 {+-} 3.4%, n = 11), based on the starting compound [{sup 18}F]FBEM, and had a specific activity of 45.51 {+-} 16.28 GBq/{mu}mol (1.23 {+-} 0.44 Ci/{mu}mol, n = 7) at the end of synthesis. The C-terminal isomer, [{sup 18}F]FBEM-[Cys{sup 40}]-exendin-4, had higher affinity for INS-1 tumor cells (IC{sub 50} 1.11 {+-} 0.057 nM) and higher tumor uptake (25.25 {+-} 3.39 %ID/g at 1 h) than the N-terminal isomer, [{sup 18}F]FBEM-[Cys{sup 0}]-exendin-4 (IC{sub 50} 2.99 {+-} 0.06 nM, uptake 7.20 {+-} 1.26 %ID/g at 1 h). Uptake of both isomers into INS-1 tumor, pancreas, stomach, and lung could be blocked by preinjection of nonradiolabeled [Cys{sup x}]-exendin-4 (p < 0.05). [{sup 18}F]FBEM-[Cys{sup 40}]-exendin-4 and [{sup 18}F]FBEM-[Cys{sup 0}]-exendin-4 have high affinity for GLP-1R and display similar in vitro cell internalization. The higher uptake into INS-1 xenograft tumors

Para neoplastic cataplexy: evolution of PET with [{sup 18}F] -F.D.G. imaging; Cataplexie paraneoplasique: evolution de l'imagerie TEP au [18F]-FDG

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Farida, K.; Fernandez, P.; Guyot, M.; Jeandot, R.; Allard, M. [Service de medecine nucleaire, CHU de Bordeaux, (France); Sibon, I. [service de neurologie, CHU de Bordeaux, (France)

2009-05-15

Cataplexy is sudden and transient episode of loss of muscle tone, often triggered by emotions. We find it in the Gelineau disease but it can be constitutes an exceptional clinical expression of para-neoplasic syndromes. We report the evolution of the PET imaging for a patient during a para-neoplasic syndrome secondary to a testes teratoma associated to the presence of antibodies anti-Ma2. Different aspects of the {sup 18}F-F.D.G. fixation can be observed during the para-neoplasic syndromes affecting the central nervous system. Their values in term of prognosis and help to the therapy decision are still to define. (N.C.)

Uptake of [18F]fluorodeoxyglucose in human monocyte-macrophages in vitro

International Nuclear Information System (INIS)

Deichen, Jan Thiess; Prante, Olaf; Gack, Michaela; Schmiedehausen, Kristin; Kuwert, Torsten

2003-01-01

The fact that fluorine-18 fluorodeoxyglucose ([ 18 F]FDG) accumulates in inflammatory lesions as well as in tumours reduces the diagnostic specificity of positron emission tomography (PET) in oncology. The aim of this study was to characterise the uptake of [ 18 F]FDG in isolated human monocyte-macrophages (HMMs) in vitro in comparison with that in human glioblastoma (GLI) and pancreatic carcinoma cells (PAN). The purity of HMM preparations was determined by immunohistochemical staining and their functional integrity was assessed by long-term incubation with iodine-131 acetylated bovine serum albumin. [ 18 F]FDG uptake in HMMs was quantified as percent of whole [ 18 F]FDG activity per well (% ID) or as % ID in relation to total protein mass. [ 18 F]FDG uptake in HMMs significantly increased with culture duration, yielding 7.5%±0.9% (% ID/100 μg) at day 14. Stimulation by lipopolysaccharide further enhanced [ 18 F]FDG uptake in HMMs by a factor of 2. [ 18 F]FDG uptake significantly decreased with increasing glucose concentration in the medium. Radio-thin layer chromatography of intracellular metabolites revealed that [ 18 F]FDG was trapped by HMMs mainly as [ 18 F]FDG-6-phosphate and [ 18 F]FDG-1,6-diphosphate. [ 18 F]FDG uptake was in the range of uptake values measured in GLI and PAN. By accumulating [ 18 F]FDG in a manner analogous to uptake by tumour cells, activated HMMs may contribute to the [ 18 F]FDG uptake values measured by PET in neoplasms. (orig.)

Estimation of patient dose in 18 F-FDG and 18 F-FDOPA PET/CT examinations

Directory of Open Access Journals (Sweden)

Aruna Kaushik

2013-01-01

Full Text Available Purpose: To estimate specific organ and effective doses to patients resulting from the 18 F-FDG ( 18 F-2-deoxy-D-glucose and 18 F-FDOPA (6-fluoro-( 18 F-L-3, 4-dihydroxyphenylalanine PET/CT examinations for whole body and brain. Materials and Methods: Three protocols for whole body and three for brain PET/CT were used. The CTDI values were measured using standard head and body CT phantoms and also computed using a software CT-Expo for dose evaluation from the CT component. OLINDA software based on MIRD method was used for estimating doses from the PET component of the PET/CT examination. Results: The organ doses from 18 F-FDG and 18 F-FDOPA whole body and brain PET/CT studies were estimated. The total effective dose from a typical protocol of whole body PET/CT examination was 14.4 mSv for females and 11.8 mSv for male patients from 18 F-FDG, whereas it was 11 mSv for female and 9.1 mSv for male patients from 18 F-FDOPA. The total effective doses from a typical protocol for PET/CT studies of brain was 6.5 mSv for females and 5.1 mSv for males from 18 F-FDG whereas it was 3.7 mSv for females and 2.8 mSv for males from 18 F-FDOPA. Conclusions: The effective radiation doses from whole body PET/CT examination was approximately 4-8 times higher than the background radiation dose from both 18 F-FDG and 18 F-FDOPA scans, while it was 1-3 times the background radiation dose from PET/CT scans of brain.

High susceptibility prevalence for F4+ and F18+Escherichia coli in Flemish pigs.

Science.gov (United States)

Nguyen, Ut V; Coddens, Annelies; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Poucke, Mario Van; Peelman, Luc; Cox, Eric

2017-04-01

F4 and/or F18 enterotoxigenic Escherichia coli (F4 + /F18 + ETEC) are responsible for diarrhea while F18 + verotoxigenic E. coli (F18 + VTEC) cause edema disease in pigs. Both infections can result in severe economic losses, which are mainly the result of the medication, growth retardation and mortality. The susceptibility of piglets to these pathogens is determined by the presence of F4 and F18 receptors (F4R and F18R). Understanding the composition of the susceptibility phenotypes of pigs is useful for animal health and breeding management. This study aimed to determine the prevalence of the F4 ETEC susceptibility phenotypes and F18 + E. coli susceptibility among Flemish pig breeds by using the in vitro villous adhesion assay. In this study, seven F4 ETEC susceptibility phenotypes were found, namely A (F4 ab R + , ac R + , ad R + ; 59.16%), B (F4 ab R + , ac R + , ad R - ; 6.28%), C (F4 ab R + , ac R - , ad R + ; 2.62%), D (F4 ab R - , ac R - , ad R + ; 6.28%), E (F4 ab R - , ac R - , ad R - ; 24.08%), F (F4 ab R + , ac R - , ad R - ; 1.05%) and G (F4 ab R - , ac R + , ad R - ; 0.52%). F4ab and F4ac E. coli showed a stronger degree of adhesion to the intestinal villi (53.40% and 52.88% strong adhesion, respectively), compared to F4ad E. coli (43.46% strong adhesion). Furthermore, the correlation between F4ac and F4ab adhesion was higher (r=0.78) than between F4ac and F4ad adhesion (r=0.41) and between F4ab and F4ad adhesion (r=0.57). For F18 + E. coli susceptibility, seven out of 82 pigs were F18R negative (8.54%), but only two of these seven pigs (2.44%) were also negative for F4R. As such, the chance to identify a pig that is positive for a F4 ETEC variant or F18 + E. coli is 97.56%. Therefore, significant economic losses will arise due to F4 + and/or F18 + E. coli infections in the Flemish pig population due to the high susceptibility prevalence. Copyright © 2016 Elsevier B.V. All rights reserved.

The environmental survey manual: Appendices E, F, G, H, I, J, and K

International Nuclear Information System (INIS)

1987-08-01

Appendices E, F, G, H, I, J and K of the Environmental Survey Manual address the following topics: Field Sampling Protocols and Guidance; Guidelines for Preparation of Quality Assurance Plans; Decontamination Guidance; Data Management and Analysis; Sample and Document Management; Health and Safety Guidance for Sampling and Analysis Teams; Documents for Sampling and Analysis Program

Quantitative measurement of 18F-FDG PET/CT uptake reflects the expansion of circulating plasmablasts in IgG4-related disease.

Science.gov (United States)

Berti, Alvise; Della-Torre, Emanuel; Gallivanone, Francesca; Canevari, Carla; Milani, Raffaella; Lanzillotta, Marco; Campochiaro, Corrado; Ramirez, Giuseppe Alvise; Bozzalla Cassione, Emanuele; Bozzolo, Enrica; Pedica, Federica; Castiglioni, Isabella; Arcidiacono, Paolo Giorgio; Balzano, Gianpaolo; Falconi, Massimo; Gianolli, Luigi; Dagna, Lorenzo

2017-12-01

[18F]Fluorodeoxyglucose (18F-FDG) PET/CT is increasingly used to assess organ involvement and response to treatment in IgG4-related disease (IgG4-RD), but clear correlations between 18F-FDG uptake and disease activity have not been established yet. We aimed to correlate the intensity and distribution of 18F-FDG uptake with validated clinical, serological and immunological parameters of IgG4-RD activity. Twenty patients with active IgG4-RD underwent a baseline 18F-FDG PET/CT. Ten patients repeated 18F-FDG PET/CT after immunosuppressive treatments. 18F-FDG tissue uptake was measured using the standardized uptake value corrected for the partial volume effect (PVC-SUV) and the total lesion glycolysis (TLG) with (TLGtot+ln) and without (TLGtot-ln) lymph nodes. Disease activity was assessed by means of clinical parameters [IgG4-RD Responder Index (RI)], serological (ESR and CRP) and immunological (serum IgG4 and circulating plasmablasts) biomarkers. The enhanced liver fibrosis score was exploited as a biomarker for fibroblast activation. Thirteen (65%) patients had two or more organs affected by IgG4-RD. All patients had active IgG4-RD as defined by a median IgG4-RD RI value of 9 (range 6-15; normal IgG4 and plasmablasts were elevated in 85% of patients. Circulating plasmablasts positively correlated with PVC-SUV (P = 0.027), inversely correlated with TLGtot-ln (P = 0.023) and did not correlate with TLGtot+ln (P > 0.05). No statistically significant correlation was found between PVC-SUV or TLG and IgG4-RD RI, ESR, CRP, serum IgG4 or enhanced liver fibrosis score (P > 0.05). Clinical response to immunosuppressive therapies was associated with a consensual reduction of circulating plasmablasts, PVC-SUV, TLGtot+ln and TLGtot-ln values (P IgG4-RD lesions reflects immunological perturbations of the B cell compartment rather than fibroblast activation and extracellular matrix deposition. Conventional biomarkers of disease activity, namely IgG4-RD RI, ESR, CRP and serum IgG4

Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [18F]ICF01006, a highly promising melanoma PET tracer

International Nuclear Information System (INIS)

Rbah-Vidal, Latifa; Vidal, Aurelien; Besse, Sophie; Audin, Laurent; Degoul, Francoise; Miot-Noirault, Elisabeth; Moins, Nicole; Auzeloux, Philippe; Chezal, Jean-Michel; Cachin, Florent; Bonnet, Mathilde; Askienazy, Serge; Dolle, Frederic

2012-01-01

Here, we report a new and rapid radiosynthesis of 18 F-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([ 18 F]ICF01006), a molecule with a high specificity for melanotic tissue, and its evaluation in a murine model for early specific detection of pigmented primary and disseminated melanoma. [ 18 F]ICF01006 was synthesized using a new one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumour) or intravenous (lung colonies) injection of B16BL6 melanoma cells in C57BL/6J mice. The relevance and sensitivity of positron emission tomography (PET) imaging using [ 18 F]ICF01006 were evaluated at different stages of tumoural growth and compared to 18 F-fluorodeoxyglucose ([ 18 F]FDG). The fully automated radiosynthesis of [ 18 F]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity >99 % (specific activity 70-80 GBq/μmol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [ 18 F]ICF01006 tumoural uptake of 1.64 ± 0.57, 3.40 ± 1.47 and 11.44 ± 2.67 percentage of injected dose per gram of tissue (%ID/g) at days 3, 5 and 14, respectively. [ 18 F]ICF01006 PET imaging also allowed detection of melanoma pulmonary colonies from day 9 after tumour cell inoculation, with a lung radiotracer accumulation correlated with melanoma invasion. At day 21, radioactivity uptake in lungs reached a value of 5.23 ± 2.08 %ID/g (versus 0.41 ± 0.90 %ID/g in control mice). In the two models, comparison with [ 18 F]FDG showed that both radiotracers were able to detect melanoma lesions, but [ 18 F]ICF01006 was superior in terms of contrast and specificity. Our promising results provide further preclinical data, reinforcing the excellent potential of [ 18 F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma. (orig.)

Fast and repetitive in-capillary production of [18F]FDG.

Science.gov (United States)

Wester, Hans-Jürgen; Schoultz, Bent Wilhelm; Hultsch, Christina; Henriksen, Gjermund

2009-04-01

The increasing demand for radiopharmaceuticals to be provided reproducibly and flexibly with high frequency for clinical application and animal imaging would be better met by improved or even new strategies for automated tracer production. Radiosynthesis in microfluidic systems, i.e. narrow tubing with a diameter of approximately 50-500 microm, holds promise for providing the means for repetitive multidose and multitracer production. In this study, the performance of a conceptually simple microfluidic device integrated into a fully automated synthesis procedure for in-capillary radiosynthesis (ICR) of clinical grade [(18)F]FDG was evaluated. The instrumental set-up consisted of pumps for reagent and solvent delivery into small mixing chambers, micro-fluidic capillaries, in-process radioactivity monitoring, solid-phase extraction and on-column deprotection of the (18)F-labelled intermediate followed by on-line formulation of [(18)F]FDG. In-capillary(18)F-fluorination of 2.1 micromol 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulphonyl-beta-D-mannopyranose (TATM; precursor for [(18)F]FDG) in acetonitrile (MeCN) at a flow rate of 0.3 ml/min within 40 s and subsequent on-line hydrolysis of the intermediate by treatment with 0.3 M NaOH for 1 min at 40 degrees C resulted in a radiochemical yield of 88 +/- 4% within 97%, MeCN <5 microg/ml) and similar absolute yields (approximately 1.4 GBq). The described ICR process is a simple and efficient alternative to classic radiotracer production systems and provides a comparatively cheap instrumental methodology for the repetitive production of [(18)F]FDG with remarkably high efficiency and high yield under fully automated conditions. Although the results concerning the levels of activity need to be confirmed after installation of the equipment in a suitable GMP hot-cell environment, we expect the instrumental design to allow up-scaling without major difficulties or fundamental restrictions. Furthermore, we are convinced that

Evaluation of TSPO PET Ligands [18F]VUIIS1009A and [18F]VUIIS1009B: Tracers for Cancer Imaging.

Science.gov (United States)

Tang, Dewei; Li, Jun; Buck, Jason R; Tantawy, Mohamed Noor; Xia, Yan; Harp, Joel M; Nickels, Michael L; Meiler, Jens; Manning, H Charles

2017-08-01

Positron emission tomography (PET) ligands targeting translocator protein (TSPO) are potential imaging diagnostics of cancer. In this study, we report two novel, high-affinity TSPO PET ligands that are 5,7 regioisomers, [ 18 F]VUIIS1009A ([ 18 F]3A) and [ 18 F]VUIIS1009B ([ 18 F]3B), and their initial in vitro and in vivo evaluation in healthy mice and glioma-bearing rats. VUIIS1009A/B was synthesized and confirmed by X-ray crystallography. Interactions between TSPO binding pocket and novel ligands were evaluated and compared with contemporary TSPO ligands using 2D 1 H- 15 N heteronuclear single quantum coherence (HSQC) spectroscopy. In vivo biodistribution of [ 18 F]VUIIS1009A and [ 18 F]VUIIS1009B was carried out in healthy mice with and without radioligand displacement. Dynamic PET imaging data were acquired simultaneously with [ 18 F]VUIIS1009A/B injections in glioma-bearing rats, with binding reversibility and specificity evaluated by radioligand displacement. In vivo radiometabolite analysis was performed using radio-TLC, and quantitative analysis of PET data was performed using metabolite-corrected arterial input functions. Imaging was validated with histology and immunohistochemistry. Both VUIIS1009A (3A) and VUIIS1009B (3B) were found to exhibit exceptional binding affinity to TSPO, with observed IC 50 values against PK11195 approximately 500-fold lower than DPA-714. However, HSQC NMR suggested that VUIIS1009A and VUIIS1009B share a common binding pocket within mammalian TSPO (mTSPO) as DPA-714 and to a lesser extent, PK11195. [ 18 F]VUIIS1009A ([ 18 F]3A) and [ 18 F]VUIIS1009B ([ 18 F]3B) exhibited similar biodistribution in healthy mice. In rats bearing C6 gliomas, both [ 18 F]VUIIS1009A and [ 18 F]VUIIS1009B exhibited greater binding potential (k 3 /k 4 )in tumor tissue compared to [ 18 F]DPA-714. Interestingly, [ 18 F]VUIIS1009B exhibited significantly greater tumor uptake (V T ) than [ 18 F]VUIIS1009A, which was attributed primarily to greater plasma

Preparation and evaluation of ethyl [{sup 18}F]fluoroacetate as a proradiotracer of [{sup 18}F]fluoroacetate for the measurement of glial metabolism by PET

Energy Technology Data Exchange (ETDEWEB)

Mori, Tetsuya [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Sun, Li-Quan [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); School of Life Science and Technology, Beijing Institute of Technology, Beijing 100081 (China); Kobayashi, Masato [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Kiyono, Yasushi [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan)], E-mail: ykiyono@u-fukui.ac.jp; Okazawa, Hidehiko; Furukawa, Takako [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Kawashima, Hidekazu [Graduate School of Medicine, Kyoto University, Kyoto 606-8501 (Japan); Welch, Michael J. [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Fujibayashi, Yasuhisa [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan)

2009-02-15

Introduction: Changes in glial metabolism in brain ischemia, Alzheimer's disease, depression, schizophrenia, epilepsy and manganese neurotoxicity have been reported in recent studies. Therefore, it is very important to measure glial metabolism in vivo for the elucidation and diagnosis of these diseases. Radiolabeled acetate is a good candidate for this purpose, but acetate has little uptake in the brain due to its low lipophilicity. We have designed a new proradiotracer, ethyl [{sup 18}F]fluoroacetate ([{sup 18}F]EFA), which is [{sup 18}F]fluoroacetate ([{sup 18}F]FA) esterified with ethanol, to increase the lipophilicity of fluoroacetate (FA), allowing the measurement of glial metabolism. Methods: The synthesis of [{sup 18}F]EFA was achieved using ethyl O-mesyl-glycolate as precursor. The blood-brain barrier permeability of ethyl [1-{sup 14}C]fluoroacetate ([{sup 14}C]EFA) was estimated by a brain uptake index (BUI) method. Hydrolysis of [{sup 14}C]EFA in the brain was calculated by the fraction of radioactivity in lipophilic and water fractions of homogenized brain. Using the plasma of five animal species, the stability of [{sup 14}C]EFA was measured. Biodistribution studies of [{sup 18}F]EFA in ddY mice were carried out and compared with [{sup 18}F]FA. Positron emission tomography (PET) scanning using common marmosets was performed for 90 min postadministration. At 60 min postinjection of [{sup 18}F]EFA, metabolite studies were performed. Organs were dissected from the marmosets, and extracted metabolites were analyzed with a thin-layer chromatography method. Results: The synthesis of [{sup 18}F]EFA was accomplished in a short time (29 min) and with a reproducible radiochemical yield of 28.6{+-}3.6% (decay corrected) and a high radiochemical purity of more than 95%. In the brain permeability study, the BUI of [{sup 14}C]EFA was 3.8 times higher than that of sodium [1-{sup 14}C]fluoroacetate. [{sup 14}C]EFA was hydrolyzed rapidly in rat brains. In stability

Radiosynthesis of [18F]fluorophenyl-L-amino acids by isotopic exchange on carbonyl-activated precursors

International Nuclear Information System (INIS)

Castillo Melean, Johnny

2011-01-01

Aromatic [ 18 F]fluoroamino acids have earlier been developed as promising probes for diagnostics using PET. However, a wider use of these radiofluorinated compounds has been limited due to radiosynthetic constraints. The work here presents an amenable three-step radiosynthesis pathway for the preparation of 2-[ 18 F]fluoro-L-phenylalanine (2-[ 18 F]Fphe), 2-[ 18 F]fluoro-L-tyrosine (2-[ 18 F]Ftyr), 6-[ 18 F]fuoro-L-m-tyrosine (6-[ 18 F]Fmtyr) and 6-[ 18 F]fluoro-L-DOPA (6-[ 18 F]FDOPA). For this, corresponding precursors were 18 F-fluorinated by nucleophilic isotopic exchange, followed by either removal of an activating formyl group with Rh(PPh 3 ) 3 Cl or its conversion by Baeyer-Villiger oxidation, respectively, and subsequent hydrolysis of protecting groups in acidic medium. Two efficient synthetic approaches were developed for the preparation of highly functionalized fluoro-benzaldehydes and -ketones which were used as labeling precursors. The compounds (2S,5S)-tert-butyl 2-tert-butyl-5-(2-fluoro-5-formylbenzyl)-3-methyl-4-oxoimidazolidine-1 -carboxylate (1a), (2S,5S)-tert-butyl 5-(5-acetyl-2-fluorobenzyl)-2-tert-butyl-3-methyl-4-oxoimidazolidine-1 -carboxylate (1c), (2S,5S)-benzyl 2-tert-butyl-5-(2-fluoro-5-formylbenzyl)-3-methyl-4-oxoimidazolidine-1 -carbo-xylate (1d), 4-fluoro-3-(((2S,5R)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazin-2-yl) me-thyl)b enzal-dehyde (1e) and 1-(4-fluoro-3-(((2S,5R)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazin-2-yl) me-thy l)phenyl)ethanone (1f), could be prepared in six steps and overall yields of 41%, 48%, 37%, 27%, and 32%, respectively. (2S,5S)-tert-Butyl 5-(4-(benzyloxy)-2-fluoro-5-formylbenzyl)-2-tert-butyl-3-methyl-4 -oxoimidazolidi ne-1-carboxylate (1b) was prepared in ten steps with an overall yield of 19% while compounds (2S,5S)-tert-butyl 5-(5-(3,5-bis(trifluoromethyl)-benzoyl)-2-fluorobenzyl)-2-tert-butyl-3 -methyl-4-oxoimidazolidine-1-carboxylate (1g) and (2S,5S)-tert-butyl 2-tert-butyl-5-(2-fluoro-5

In vivo evaluation in rats of [{sup 18}F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine as a potential radiotracer for PET assessment of CNS sigma-1 receptors

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Waterhouse, Rikki N. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States) and Department of Radiology, Columbia University, New York, NY 10032 (United States) and Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States)]. E-mail: rnw7@columbia.edu; Chang, Raymond C. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States); Zhao, Jun [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States); Carambot, Patty E. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States)

2006-02-15

Introduction: Sigma-1 receptors are expressed throughout the mammalian central nervous system (CNS) and are implicated in several psychiatric disorders, including schizophrenia and depression. We have recently evaluated the high-affinity (K {sub D}=0.5{+-}0.2 nM, log P=2.9) sigma-1 receptor radiotracer [{sup 18}F]1-(3-fluoropropyl)-4-(4-cyanophenoxymethyl)piperidine, [{sup 18}F]FPS, in humans. In contrast to appropriate kinetics exhibited in baboon brain, in the human CNS, [{sup 18}F]FPS does not reach pseudoequilibrium by 4 h, supporting the development of a lower-affinity tracer [Waterhouse RN, Nobler MS, Chang RC, Zhou Y, Morales O, Kuwabara H, et al. First evaluation of the sigma-1 receptor radioligand [{sup 18}F]1-3-fluoropropyl-4-((4-cyanophenoxy)-methyl)piperidine ([{sup 18}F]FPS) in healthy humans. Neuroreceptor Mapping 2004, July 15-18th, Vancouver, BC Canada 2004]. We describe herein the in vivo evaluation in rats of [{sup 18}F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine ([{sup 18}F]SFE) (K {sub D}=5 nM, log P=2.4), a structurally similar, lower-affinity sigma-1 receptor radioligand. Methods: [{sup 18}F]SFE was synthesized (n=4) as previously described in good yield (54{+-}6% EOB), high specific activity (2.1{+-}0.6 Ci/{mu}mol EOS) and radiochemical purity (98{+-}1%) and evaluated in awake adult male rats. Results: Similar to [{sup 18}F]FPS, regional brain radioactivity concentrations [percentage of injected dose per gram of tissue (%ID/g), 15 min] for [{sup 18}F]SFE were highest in occipital cortex (1.86{+-}0.06 %ID/g) and frontal cortex (1.76{+-}0.38 %ID/g), and lowest in the hippocampus (1.01{+-}0.02%ID/g). Unlike [{sup 18}F]FPS, [{sup 18}F]SFE cleared from the brain with {approx}40% reduction in peak activity over a 90-min period. Metabolite analysis (1 h) revealed that [{sup 18}F]SFE was largely intact in the brain. Blocking studies showed a large degree (>80%) of saturable binding for [{sup 18}F]SFE in discrete brain regions. Conclusions

18F-Labelled metomidate analogues as adrenocortical imaging agents

International Nuclear Information System (INIS)

Erlandsson, Maria; Karimi, Farhad; Lindhe, Orjan; Langstroem, Bengt

2009-01-01

Introduction: Two- and one-step syntheses of 18 F-labelled analogues of metomidate, such as 2-[ 18 F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[ 18 F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[ 18 F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[ 18 F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[ 18 F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented. Methods: Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[ 18 F]fluoroethyl 4-methylbenzenesulfonate or 3-[ 18 F]fluoropropyl 4-methylbenzenesulfonate. These were used as 18 F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3. Results: The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46±3% and 79±30%, respectively. Conclusion: Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.

A Pilot Trial of Humanized Anti-GD2 Monoclonal Antibody (hu14.18K322A) with Chemotherapy and Natural Killer Cells in Children with Recurrent/Refractory Neuroblastoma.

Science.gov (United States)

Federico, Sara M; McCarville, M Beth; Shulkin, Barry L; Sondel, Paul M; Hank, Jacquelyn A; Hutson, Paul; Meagher, Michael; Shafer, Aaron; Ng, Catherine Y; Leung, Wing; Janssen, William E; Wu, Jianrong; Mao, Shenghua; Brennan, Rachel C; Santana, Victor M; Pappo, Alberto S; Furman, Wayne L

2017-11-01

Purpose: Anti-GD2 mAbs, acting via antibody-dependent cell-mediated cytotoxicity, may enhance the effects of chemotherapy. This pilot trial investigated a fixed dose of a unique anti-GD2 mAb, hu14.18K322A, combined with chemotherapy, cytokines, and haploidentical natural killer (NK) cells. Experimental Design: Children with recurrent/refractory neuroblastoma received up to six courses of hu14.18K322A (40 mg/m 2 /dose, days 2-5), GM-CSF, and IL2 with chemotherapy: cyclophosphamide/topotecan (courses 1,2), irinotecan/temozolomide (courses 3,4), and ifosfamide/carboplatin/etoposide (courses 5,6). Parentally derived NK cells were administered with courses 2, 4, and 6. Serum for pharmacokinetic studies of hu14.18K322A, soluble IL2 receptor alpha (sIL2Rα) levels, and human antihuman antibodies (HAHA) were obtained. Results: Thirteen heavily pretreated patients (9 with prior anti-GD2 therapy) completed 65 courses. One patient developed an unacceptable toxicity (grade 4 thrombocytopenia >35 days). Four patients discontinued treatment for adverse events (hu14.18K322A allergic reaction, viral infection, surgical death, second malignancy). Common toxicities included grade 3/4 myelosuppression (13/13 patients) and grade 1/2 pain (13/13 patients). Eleven patients received 29 NK-cell infusions. The response rate was 61.5% (4 complete responses, 1 very good partial response, 3 partial responses) and five had stable disease. The median time to progression was 274 days (range, 239-568 days); 10 of 13 patients (77%) survived 1 year. Hu14.18K322A pharmacokinetics was not affected by chemotherapy or HAHA. All patients had increased sIL2Rα levels, indicating immune activation. Conclusions: Chemotherapy plus hu14.18K322A, cytokines, and NK cells is feasible and resulted in clinically meaningful responses in patients with refractory/recurrent neuroblastoma. Further studies of this approach are warranted in patients with relapsed and newly diagnosed neuroblastoma. Clin Cancer Res; 23

1-[18F]fluoro-2-propanol p-toluenesulfonate: a synthon for the preparation of N-([18F]fluoroisopropyl)amines

International Nuclear Information System (INIS)

Groot, T.J. de; Elsinga, P.H.; Visser, G.M.; Vaalburg, W.

1992-01-01

The new radiochemical synthon 1-[ 18 F]fluoro-2-propanol p-toluenesulfonate is prepared with a radiochemical yield of 45% [corrected for decay to beginning of synthesis, synthesis time 40 min]. This compound is used to prepare the [ 18 F]fluoroisopropyl-alkylated derivatives of benzylamine and norephedrine with a yield of 7 and 2% respectively, (synthesis time 90 min). This alkylation reaction a good perspective for the preparation of [ 18 F]fluoro-labelled analogues of β 1 -adrenergic receptor binding ligands for PET. (Author)

IgG4-associated multifocal systemic fibrosis detected by cancer screening with 18F-FDG positron emission tomography/computed tomography

International Nuclear Information System (INIS)

Soga, Shigeyoshi; Kita, Tamotsu; Hiratsuka, Miyuki; Sakaguchi, Chiharu; Shinmoto, Hiroshi; Kosuda, Shigeru; Sakata, Ikuko; Miura, Soichiro

2010-01-01

Serial fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) studies were performed with an interval of one year in a 62-year-old man with IgG4-associated multifocal systemic fibrosis (IMSF). He first underwent 18 F-FDG PET/CT cancer screening, which revealed multiple 18 F-FDG-avid uptakes in the pancreas, prostate, and lymph nodes in the upper mediastinum, pulmonary hila, porta hepatis, and the left iliac and inguinal regions. He was not symptomatic at this initial examination. The follow-up 18 F-FDG PET/CT study showed disappearance of 18 F-FDG-avid uptake foci in the pancreas despite no treatment having been administered, but demonstrated new lesions in the abdominal para-aortic region and more intense FDG uptake in the porta hepatis lesion. Serial 18 F-FDG PET/CT studies might be useful in monitoring patients with IMSF, as well as evaluating the state of systemic involvement. Findings of 18 F-FDG PET/CT may provide information useful for determining the optimal initiation of IMSF treatment. (author)

The effect of P-glycoprotein on 18F-FDG uptake in vitro

International Nuclear Information System (INIS)

Yu Chunjing; Zhang Bin; Deng Shengming; Wan Weixing; Wu Yiwei

2013-01-01

Objective: To evaluate the effect of P-gp inhibitors of verapamil (VER) and GF120918 on 18 F-FDG uptake in Bcap37 and Bcap37/multidrug resistance (MDR)1 cell lines in vitro, and to explore the relationship between 18 F-FDG uptake and P-gp expression at cellular level. Methods: Bcap37 and Bcap37/MDR1 cells were seeded into 6-well plates at a density of 1 × 10 6 per well. Three days later,37 kBq/ml 18 F-FDG, or 37 kBq/ml 18 F-FDG + 100 μmol/L VER, or 37 kBq/ml 18 F-FDG + 50 μmol/L GF120918 were added into each well. After incubated for 10, 30, 60 and 120 min at 37 ℃ and in 5% CO 2 , the medium was removed and the cells were washed three times with 1 ml ice-cold PBS immediately. The radioactivity of 18 F-FDG was measured using a gamma counter. The uptake of 18 F-FDG was expressed as the ratio of 18 F-FDG radioactivity in Bcap37 or Bcap37/MDR1 cells and the overall radioactivity added to the cells in each well.The t test was used for statistical analysis. Results: 18 F-FDG uptake was higher in Bcap37/MDR1 cells than that in Bcap37 cells after incubated for 10 min. The uptake rate was (1.88 ±0.19) % in Bcap37/MDR1 cells and (1.37 ± 0.18) % in Bcap37 cells (t=7.832, P<0.05). On the contrary, 18 F-FDG uptake was significantly higher in Bcap37 cells than that in Bcap37/MDR1 cells after incubated for 60 and 120 min. The uptake rates were (2.29 ±0.23)% and (2.34 ±0.15)% in Bcap37 cells, (1.47 ±0.14)% and (1.53 ±0.22)% in Bcap37/MDR1 cells (t=8.437, 8.283, both P<0.05). 18 F-FDG uptake was significantly higher with VER or GF120918 in Bcap37/MDR1 cells than that without VER or GF120918 after the incubation of 60 and 120 min (t=9.032, 9.243 and 8.765, 8.803, all P<0.05). The uptake rates with VER or GF120918 were (2.45 ±0.21)% and (2.46 ±0.25)%, (2.50 ±0.24)% and (2.48 ±0.27)%. There was no significant difference of 18 F-FDG uptake in Bcap37 cells with or without VER or GF120918. Conclusions: 18 F-FDG is a substrate of P-gp at cellular level. P-gp may act as an

Quantitative analysis of 18F-NaF dynamic PET/CT cannot differentiate malignant from benign lesions in multiple myeloma.

Science.gov (United States)

Sachpekidis, Christos; Hillengass, Jens; Goldschmidt, Hartmut; Anwar, Hoda; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2017-01-01

A renewed interest has been recently developed for the highly sensitive bone-seeking radiopharmaceutical 18 F-NaF. Aim of the present study is to evaluate the potential utility of quantitative analysis of 18 F-NaF dynamic PET/CT data in differentiating malignant from benign degenerative lesions in multiple myeloma (MM). 80 MM patients underwent whole-body PET/CT and dynamic PET/CT scanning of the pelvis with 18 F-NaF. PET/CT data evaluation was based on visual (qualitative) assessment, semi-quantitative (SUV) calculations, and absolute quantitative estimations after application of a 2-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). In total 263 MM lesions were demonstrated on 18 F-NaF PET/CT. Semi-quantitative and quantitative evaluations were performed for 25 MM lesions as well as for 25 benign, degenerative and traumatic lesions. Mean SUV average for MM lesions was 11.9 and mean SUV max was 23.2. Respectively, SUV average and SUV max for degenerative lesions were 13.5 and 20.2. Kinetic analysis of 18 F-NaF revealed the following mean values for MM lesions: K 1 = 0.248 (1/min), k 3 = 0.359 (1/min), influx (K i ) = 0.107 (1/min), FD = 1.382, while the respective values for degenerative lesions were: K 1 = 0.169 (1/min), k 3 = 0.422 (1/min), influx (K i ) = 0.095 (1/min), FD = 1. 411. No statistically significant differences between MM and benign degenerative disease regarding SUV average , SUV max , K 1 , k 3 and influx (K i ) were demonstrated. FD was significantly higher in degenerative than in malignant lesions. The present findings show that quantitative analysis of 18 F-NaF PET data cannot differentiate malignant from benign degenerative lesions in MM patients, supporting previously published results, which reflect the limited role of 18 F-NaF PET/CT in the diagnostic workup of MM.

Evaluation of an [18F]AlF-NOTA Analog of Exendin-4 for Imaging of GLP-1 Receptor in Insulinoma

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Dale O. Kiesewetter, Ning Guo, Jinxia Guo, Haokao Gao, Lei Zhu, Ying Ma, Gang Niu, Xiaoyuan Chen

2012-01-01

Full Text Available Introduction: The GLP-1 receptor plays an important role in glucose homeostasis and thus is a very important target for diabetes therapy. The receptor is also overexpressed in insulinoma, a tumor of pancreatic beta-cells. We previously evaluated two fluorine-18-labeled analogs of exendin-4 prepared by conjugation with [18F]FBEM (N-[2-(4-[18F]fluorobenzamideethyl]maleimide. Both compounds demonstrated good tumor uptake, but the synthesis of the radiotracers was time consuming. To overcome this challenge, we developed a NOTA analog and performed radiolabeling using aluminum [18F]fluoride complexation.Methods: Cys40-exendin-4 was conjugated with NOTA mono N-ethylmaleimide. [18F]AlF conjugation was conducted and the radiolabeled product purified by preparative HPLC. Dynamic and static PET imaging scans were conducted on nude mice with established INS-1 xenografts. Uptake of tumor and other major organs in static images was quantitated (%ID/g and comparison with blocking studies was made. PET quantification was also compared with ex vivo biodistribution results.Results: The radiosynthesis provided [18F]AlF-NOTA-MAL-cys40-exendin-4 in 23.6 ± 2.4 % radiochemical yield (uncorrected, n = 3 after HPLC; the process required about 55 min. The specific activity at time of injection ranged from 19.6 to 31.4 GBq (0.53-0.85 Ci/µmol. Tumor uptake had reached its maximum (16.09 ± 1.18% ID/g, n = 4 by 5 min and remained nearly constant for the duration of the study. Kidney uptake continued to increase throughout the entire one hour time course. Pre-injection of exendin-4 caused a marked reduction in tissue uptake with the major exception of liver and kidneys, in which uptake was not affected. HPLC analysis of the radioactive components in extracts of the tumor and plasma showed primarily parent compound at 60 min post-injection, whereas extracts of kidney and urine contained exclusively one polar radioactive component.Conclusion: The radiotracer is prepared in

Corrosion cracking of 03N18K1M3TYu and 02N12Kh5M3 maraging steels in chloride solutions

Energy Technology Data Exchange (ETDEWEB)

Pavlov, V.N.; Chumalo, G.V.; Vereshchagin, A.N.; Melekhov, R.K.

1987-07-01

The authors investigate the electrochemical behavior in 0.5% NaCl solution and 42% MgCl/sub 2/ solution and the tendency toward corrosion cracking was determined in boiling 0.5% chloride solution of the cobalt-containing maraging steels in the title. Weld specimens and specimens of the base metal of 03N18K1M3TYu steel were tested in 3% NaCl solution for resistance to corrosion cracking. Additional investigations were made of specimens of that steel with previously created fatigue cracks of the base metal and the weld specimens in 3% NaCl solutions, since that steel is a promising material for structures operating in sea water and low concentration chloride solutions.

In vivo evaluation of 2'-deoxy-2'-[{sup 18}F]fluoro-5-iodo-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]FIAU) and 2'-deoxy-2'-[{sup 18}F]fluoro-5-ethyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]FEAU) as markers for suicide gene expression

Energy Technology Data Exchange (ETDEWEB)

Alauddin, Mian M. [University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. T8.3895, P.O. Box 059, Houston, TX (United States); Shahinian, Antranic; Park, Ryan; Fissekis, John D.; Conti, Peter S. [University of Southern California, PET Imaging Science Center, Keck School of Medicine, Los Angeles, CA (United States); Tohme, Michel [University of Southern California, PET Imaging Science Center, Keck School of Medicine, Los Angeles, CA (United States); Department of Biomedical Engineering, UC Davis, Davis, CA (United States)

2007-06-15

FIAU and FEAU were evaluated in vitro and in vivo as markers for HSV1-tk gene expression. In vitro and biodistribution studies were performed in wild type and transduced HT-29 cells using [{sup 14}C]FIAU and [{sup 3}H]FEAU. PET imaging was performed using [{sup 18}F]FIAU and [{sup 18}F]FEAU. In vitro uptake of [{sup 14}C]FIAU in tk-positive cells was 39-fold, 49-fold, and 43-fold higher (p < 0.001) than in wild type cells at 30, 60, and 120 min, respectively. Uptake of [{sup 3}H]FEAU in transduced cells was 46-fold, 62-fold, and 121-fold higher (p < 0.001) than in wild type cells at the same time points. In vivo uptake of [{sup 14}C]FIAU at 2 h in HSV1-tk positive tumors was 15.48 {+-} 3.94, 6.7-fold higher (p < 0.001) than in wild type tumors. Uptake of [{sup 3}H]FEAU in transduced tumors was 9.98 {+-} 1.99, 5.0-fold higher (p < 0.001) than in wild type tumors. Micro-PET images using [{sup 18}F]FIAU and [{sup 18}F]FEAU also showed very high uptake in HSV-tk tumors. [{sup 18}F]FIAU and [{sup 18}F]FEAU appear to be potential PET imaging agents for gene expression. (orig.)

Advanced automobile steels subjected to plate rolling at 773 K or 1373 K

Science.gov (United States)

Torganchuk, Vladimir; Belyakov, Andrey; Kaibyshev, Rustam

2017-12-01

The high manganese steels exhibiting the effects of twinning-induced plasticity (TWIP) and transformation-induced plasticity (TRIP) demonstrate an excellent combination of enhanced formability, strength and ductility. Such unique mechanical properties make high-manganese steel the most attractive material for various applications, including the segment of advanced automobile steels. The strain hardening in such steels can be achieved through martensitic transformation, when the stacking fault energy (SFE) is about 10 mJ m-2, and/or twinning, when SFE is about 20 to 50 mJ m-2. The actual mechanical properties of high-Mn steels could vary, depending on the conditions of thermo-mechanical processing. In the present study, the effect of rolling temperature on the microstructure and mechanical properties of 18% Mn steels was clarified. The steels hot rolled at 1373 K were characterized by uniform almost equiaxed grains with near random crystallographic orientations that resulted in relatively low yield strengths of 300-360 MPa, followed by pronounced strain hardening that led to the total elongation above 60%. In contrast, the steels warm rolled at 773 K were characterized by flattened grains with a strong rolling texture and high yield strengths of 850-950 MPa combined with a total elongation of about 30%.

Tritium contamination in [18O] water containing 18F produced by a cyclotron

International Nuclear Information System (INIS)

Ito, S.; Saze, T.; Sakane, H.; Nishizawa, K.

2003-01-01

Tritium in the target [ 18 O] water irradiated with 9.6 MeV protons for producing [ 18 F] fluoride by 18 O(p, n) 18 F reaction was predicted from the consideration on the Q value of the 18 O(p, t) 16 O reaction. A tritium beta ray spectrum was measured by a liquid scintillation counter equipped with a multichannel analyzer. The ratio of the 3 H activity to the 18 F activity in the [ 18 O] target water was 2.4x10 -6 at the beam current of 25μA. Tritium also was detected in the [ 18 O] water for recycling and the wasted acetonitrile [ 18 O] water. The purified [ 18 F]-FDG solution was not contaminated by 3 H. The 40% 3 H out of the produced activity was lost in the course of the [ 18 F]-FDG synthesis. It was suggested that 3 H evaporated into the air during [ 18 F]-FDG synthesis and caused contamination of the workroom. The radiation workers should be prevented from environmental 3 H contamination. (author)

Synthesis and pre-clinical evaluation of a new class of high-affinity "1"8F-labeled PSMA ligands for detection of prostate cancer by PET imaging

International Nuclear Information System (INIS)

Kelly, James; Amor-Coarasa, Alejandro; Williams, Clarence; Ponnala, Shashikanth; Nikolopoulou, Anastasia; Kim, Dohyun; Babich, John W.

2017-01-01

Current clinical imaging of PSMA-positive prostate cancer by positron emission tomography (PET) mainly features "6"8Ga-labeled tracers, notably ["6"8Ga]Ga-PSMA-HBED-CC. The longer half-life of fluorine-18 offers significant advantages over Ga-68, clinically and logistically. We aimed to develop high-affinity PSMA inhibitors labeled with fluorine-18 as alternative tracers for prostate cancer. Six triazolylphenyl ureas and their alkyne precursors were synthesized from the Glu-urea-Lys PSMA binding moiety. PSMA affinity was determined in a competitive binding assay using LNCaP cells. The ["1"8F]triazoles were isolated following a Cu(I)-catalyzed click reaction between the alkynes and ["1"8F]fluoroethylazide. The "1"8F-labeled compounds were evaluated in nude mice bearing LNCaP tumors and compared to ["6"8Ga]Ga-PSMA-HBED-CC and ["1"8F]DCFPyL. Biodistribution studies of the two tracers with the highest imaged-derived tumor uptake and highest PSMA affinity were undertaken at 1 h, 2 h and 4 h post-injection (p.i.), and co-administration of PMPA was used to determine whether uptake was PSMA-specific. F-18-labeled triazolylphenyl ureas were prepared with a decay-corrected RCY of 20-40 %, >98 % radiochemical and chemical purity, and specific activity of up to 391 GBq/μmol. PSMA binding (IC_5_0) ranged from 3-36 nM. The position of the triazole influenced tumor uptake (3 > 4 > 2), and direct conjugation of the triazole with the phenylurea moiety was preferred to insertion of a spacer group. Image-derived tumor uptake ranged from 6-14 %ID/g at 2 h p.i., the time of maximum tumor uptake; uptake of ["6"8Ga]Ga-PSMA-HBED-CC and ["1"8F]DCFPyL was 5-6 %ID/g at 1-3 h p.i., the time of maximum tumor uptake. Biodistribution studies of the two most promising compounds gave maximum tumor uptakes of 10.9 ± 1.0 % and 14.3 ± 2.5 %ID/g, respectively, as compared to 6.27 ± 1.44 %ID/g for ["6"8Ga]Ga-PSMA-HBED-CC. Six ["1"8F]triazolylphenyl ureas were prepared in good radiochemical yield

Synthesis and pre-clinical evaluation of a new class of high-affinity {sup 18}F-labeled PSMA ligands for detection of prostate cancer by PET imaging

Energy Technology Data Exchange (ETDEWEB)

Kelly, James; Amor-Coarasa, Alejandro; Williams, Clarence; Ponnala, Shashikanth [Weill Cornell Medicine, Division of Radiopharmaceutical Sciences and Molecular Imaging Innovations Institute, Department of Radiology, New York, NY (United States); Nikolopoulou, Anastasia [Weill Cornell Medicine, Division of Radiopharmaceutical Sciences and Molecular Imaging Innovations Institute, Department of Radiology, New York, NY (United States); Weill Cornell Medicine, Citigroup Biomedical Imaging Center, New York, NY (United States); Kim, Dohyun [Weill Cornell Medicine, Citigroup Biomedical Imaging Center, New York, NY (United States); Babich, John W. [Weill Cornell Medicine, Division of Radiopharmaceutical Sciences and Molecular Imaging Innovations Institute, Department of Radiology, New York, NY (United States); Weill Cornell Medicine, Citigroup Biomedical Imaging Center, New York, NY (United States); Weill Cornell Medicine, Meyer Cancer Center, New York, NY (United States)

2017-04-15

Current clinical imaging of PSMA-positive prostate cancer by positron emission tomography (PET) mainly features {sup 68}Ga-labeled tracers, notably [{sup 68}Ga]Ga-PSMA-HBED-CC. The longer half-life of fluorine-18 offers significant advantages over Ga-68, clinically and logistically. We aimed to develop high-affinity PSMA inhibitors labeled with fluorine-18 as alternative tracers for prostate cancer. Six triazolylphenyl ureas and their alkyne precursors were synthesized from the Glu-urea-Lys PSMA binding moiety. PSMA affinity was determined in a competitive binding assay using LNCaP cells. The [{sup 18}F]triazoles were isolated following a Cu(I)-catalyzed click reaction between the alkynes and [{sup 18}F]fluoroethylazide. The {sup 18}F-labeled compounds were evaluated in nude mice bearing LNCaP tumors and compared to [{sup 68}Ga]Ga-PSMA-HBED-CC and [{sup 18}F]DCFPyL. Biodistribution studies of the two tracers with the highest imaged-derived tumor uptake and highest PSMA affinity were undertaken at 1 h, 2 h and 4 h post-injection (p.i.), and co-administration of PMPA was used to determine whether uptake was PSMA-specific. F-18-labeled triazolylphenyl ureas were prepared with a decay-corrected RCY of 20-40 %, >98 % radiochemical and chemical purity, and specific activity of up to 391 GBq/μmol. PSMA binding (IC{sub 50}) ranged from 3-36 nM. The position of the triazole influenced tumor uptake (3 > 4 > 2), and direct conjugation of the triazole with the phenylurea moiety was preferred to insertion of a spacer group. Image-derived tumor uptake ranged from 6-14 %ID/g at 2 h p.i., the time of maximum tumor uptake; uptake of [{sup 68}Ga]Ga-PSMA-HBED-CC and [{sup 18}F]DCFPyL was 5-6 %ID/g at 1-3 h p.i., the time of maximum tumor uptake. Biodistribution studies of the two most promising compounds gave maximum tumor uptakes of 10.9 ± 1.0 % and 14.3 ± 2.5 %ID/g, respectively, as compared to 6.27 ± 1.44 %ID/g for [{sup 68}Ga]Ga-PSMA-HBED-CC. Six [{sup 18}F

Synthesis of [18F]-N-3-fluoro-propyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([18F]-FP-β-CIT)

International Nuclear Information System (INIS)

Fang Ping; Chen Zhengping; Lin Yansong; Zhou Xian; Du Yikui

2001-01-01

The ligand of N-(3-fluoro-propyl)-2β-carbomethoxy-3β-(4'-iodophenyl) nortropane (FP-β-CIT) and mesylate precursor were synthesized by hydrolysis of cocaine, followed by dehydration, esterification, Grignard reaction, N-demethylation, iodination, N-alkylation with 3-bromo-propanol and methyl-sulfonyl. Finally, 18 F-FP-β-CIT was prepared by nucleophilic fluorination of the mesylate with K 18 F/K 2.2.2 (Kryptofix). The labelling yield of 18 F-FP-β-CIT is 25%-30%. The total radiochemical yield of this compound, calculated from the end of bombardment (EOB) with decay correction, is 10%-12% with a synthesis time of 100-110 min. The radiochemical purity of 18 F-FP-β-CIT is greater than 90%, and this compound in aqueous solution is also stable for more than 4 hours at room temperature. It is stable enough for clinical study

Synthesis, radiofluorination and first evaluation of [{sup 18}F]fluorophenylsulfonyl- and [{sup 18}F]fluorophenylsulfinyl-piperidines as serotonin 5-HT{sub 2A} receptor antagonists for PET

Energy Technology Data Exchange (ETDEWEB)

Muehlhausen, Ute; Sihver, Wiebke [Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Juelich GmbH, 52425 Juelich (Germany); Ermert, Johannes, E-mail: j.ermert@fz-juelich.d [Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Juelich GmbH, 52425 Juelich (Germany); Coenen, Heinz H. [Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Juelich GmbH, 52425 Juelich (Germany)

2010-07-15

In psychiatric disorders, 5-HT{sub 2A} receptors play an important role. In order to study these receptors in vivo by positron emission tomography (PET), there is an increasing interest for subtype selective and high affinity radioligands. Up to now, no optimal radiotracer is available. Thus, 1-(2,4-difluorophenethyl)-4-(4-fluorophenylsulfonyl)piperidine (9), possessing high affinity and sufficient subtype selectivity for 5-HT{sub 2A} receptors, and 1-(2,4-difluorophenethyl)-4-(4-fluorophenylsulfinyl)piperidine (15) have been {sup 18}F-labelled by a nucleophilic one-step reaction. Both radiotracers could be prepared and isolated within 45 min, [{sup 18}F]9 in a radiochemical yield (RCY) of 34.5{+-}8% and [{sup 18}F]15 of 9.5{+-}2.5%. The K{sub i} values of 9 and 15 at 5-HT{sub 2A} receptors towards [{sup 3}H]ketanserin were determined to be 1.9{+-}0.6 and 198{+-}8 nM, respectively. Autoradiography with [{sup 18}F]9 and [{sup 18}F]15 on rat brain sections showed a very high nonspecific binding of >80% for [{sup 18}F]9 and 30% to 40% nonspecific binding for [{sup 18}F]15; however, it is still too high in order to compensate for its lower affinity. Even though the affinity of 9 is more promising compared with 15, the high nonspecific binding of both radiofluorinated tracers in rat brain does not recommend those as an in vivo PET imaging agent for serotonin 5-HT{sub 2A} receptors in humans.

Comparisons of [18F]-1-deoxy-1-fluoro-scyllo-inositol with [18F]-FDG for PET imaging of inflammation, breast and brain cancer xenografts in athymic mice

International Nuclear Information System (INIS)

McLarty, Kristin; Moran, Matthew D.; Scollard, Deborah A.; Chan, Conrad; Sabha, Nesrin; Mukherjee, Joydeep; Guha, Abhijit; McLaurin, JoAnne; Nitz, Mark; Houle, Sylvain; Wilson, Alan A.; Reilly, Raymond M.; Vasdev, Neil

2011-01-01

Introduction: The aim of the study was to evaluate the uptake of [ 18 F]-1-deoxy-1-fluoro-scyllo-inositol ([ 18 F]-scyllo-inositol) in human breast cancer (BC) and glioma xenografts, as well as in inflammatory tissue, in immunocompromised mice. Studies of [ 18 F]-2-fluoro-2-deoxy-D-glucose ([ 18 F]-FDG) under the same conditions were also performed. Methods: Radiosynthesis of [ 18 F]-scyllo-inositol was automated using a commercial synthesis module. Tumour, inflammation and normal tissue uptakes were evaluated by biodistribution studies and positron emission tomography (PET) imaging using [ 18 F]-scyllo-inositol and [ 18 F]-FDG in mice bearing subcutaneous MDA-MB-231, MCF-7 and MDA-MB-361 human BC xenografts, intracranial U-87 MG glioma xenografts and turpentine-induced inflammation. Results: The radiosynthesis of [ 18 F]-scyllo-inositol was automated with good radiochemical yields (24.6%±3.3%, uncorrected for decay, 65±2 min, n=5) and high specific activities (≥195 GBq/μmol at end of synthesis). Uptake of [ 18 F]-scyllo-inositol was greatest in MDA-MB-231 BC tumours and was comparable to that of [ 18 F]-FDG (4.6±0.5 vs. 5.5±2.1 %ID/g, respectively; P=.40), but was marginally lower in MDA-MB-361 and MCF-7 xenografts. Uptake of [ 18 F]-scyllo-inositol in inflammation was lower than [ 18 F]-FDG. While uptake of [ 18 F]-scyllo-inositol in intracranial U-87 MG xenografts was significantly lower than [ 18 F]-FDG, the tumour-to-brain ratio was significantly higher (10.6±2.5 vs. 2.1±0.6; P=.001). Conclusions: Consistent with biodistribution studies, uptake of [ 18 F]-scyllo-inositol was successfully visualized by PET imaging in human BC and glioma xenografts, with lower accumulation in inflammatory tissue than [ 18 F]-FDG. The tumour-to-brain ratio of [ 18 F]-scyllo-inositol was also significantly higher than that of [ 18 F]-FDG for visualizing intracranial glioma xenografts in NOD SCID mice, giving a better contrast. -- Graphical Abstract: Display Omitted

{sup 18}F-Labelled metomidate analogues as adrenocortical imaging agents

Energy Technology Data Exchange (ETDEWEB)

Erlandsson, Maria; Karimi, Farhad [Department of Biochemistry and Organic Chemistry, Uppsala University, Box 576, S-751 23 Uppsala (Sweden); Lindhe, Orjan [Uppsala Imanet, GE Healthcare, Box 967, S-751 09 Uppsala (Sweden); Langstroem, Bengt [Department of Biochemistry and Organic Chemistry, Uppsala University, Box 576, S-751 23 Uppsala (Sweden)], E-mail: bengt.langstrom@biorg.uu.se

2009-05-15

Introduction: Two- and one-step syntheses of {sup 18}F-labelled analogues of metomidate, such as 2-[{sup 18}F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[{sup 18}F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[{sup 18}F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[{sup 18}F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[{sup 18}F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented. Methods: Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[{sup 18}F]fluoroethyl 4-methylbenzenesulfonate or 3-[{sup 18}F]fluoropropyl 4-methylbenzenesulfonate. These were used as {sup 18}F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3. Results: The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46{+-}3% and 79{+-}30%, respectively. Conclusion: Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.

One-step radiosynthesis of {sup 18}F-AlF-NOTA-RGD{sub 2} for tumor angiogenesis PET imaging

Energy Technology Data Exchange (ETDEWEB)

Liu, Shuanglong; Liu, Hongguang; Xu, Yingding; Cheng, Zhen [Stanford University, Molecular Imaging Program at Stanford (MIPS), Canary Center at Stanford for Cancer Early Detection, Bio-X Program, Department of Radiology, Stanford, CA (United States); Jiang, Han [Stanford University, Molecular Imaging Program at Stanford (MIPS), Canary Center at Stanford for Cancer Early Detection, Bio-X Program, Department of Radiology, Stanford, CA (United States); Institute of Nuclear Medicine and Molecular Imaging, and the Second Affiliated Hospital of Zhejiang University School of Medicine, Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Department of Nuclear Medicine, Medical PET Center, Hangzhou, Zhejiang (China); Zhang, Hong [Institute of Nuclear Medicine and Molecular Imaging, and the Second Affiliated Hospital of Zhejiang University School of Medicine, Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Department of Nuclear Medicine, Medical PET Center, Hangzhou, Zhejiang (China)

2011-09-15

One of the major obstacles of the clinical translation of {sup 18}F-labeled arginine-glycine-aspartic acid (RGD) peptides has been the laborious multistep radiosynthesis. In order to facilitate the application of RGD-based positron emission tomography (PET) probes in the clinical setting we investigated in this study the feasibility of using the chelation reaction between Al{sup 18}F and a macrocyclic chelator-conjugated dimeric RGD peptide as a simple one-step {sup 18}F labeling strategy for development of a PET probe for tumor angiogenesis imaging. Dimeric cyclic peptide E[c(RGDyK)]{sub 2} (RGD{sub 2}) was first conjugated with a macrocyclic chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), and the resulting bioconjugate NOTA-RGD{sub 2} was then radiofluorinated via Al{sup 18}F intermediate to synthesize {sup 18}F-AlF-NOTA-RGD{sub 2}. Integrin binding affinities of the peptides were assessed by a U87MG cell-based receptor binding assay using {sup 125}I-echistatin as the radioligand. The tumor targeting efficacy and in vivo profile of {sup 18}F-AlF-NOTA-RGD{sub 2} were further evaluated in a subcutaneous U87MG glioblastoma xenograft model by microPET and biodistribution. NOTA-RGD{sub 2} was successfully {sup 18}F-fluorinated with good yield within 40 min using the Al{sup 18}F intermediate. The IC{sub 50} of {sup 19}F-AlF-NOTA-RGD{sub 2} was determined to be 46 {+-} 4.4 nM. Quantitative microPET studies demonstrated that {sup 18}F-AlF-NOTA-RGD{sub 2} showed high tumor uptake, fast clearance from the body, and good tumor to normal organ ratios. NOTA-RGD{sub 2} bioconjugate has been successfully prepared and labeled with Al{sup 18}F in one single step of radiosynthesis. The favorable in vivo performance and the short radiosynthetic route of {sup 18}F-AlF-NOTA-RGD{sub 2} warrant further optimization of the probe and the radiofluorination strategy to accelerate the clinical translation of {sup 18}F-labeled RGD peptides. (orig.)

Hypoxia imaging of uterine cervix carcinoma with (18)F-FETNIM PET/CT.

Science.gov (United States)

Vercellino, Laetitia; Groheux, David; Thoury, Anne; Delord, Marc; Schlageter, Marie-Hélène; Delpech, Yann; Barré, Emmanuelle; Baruch-Hennequin, Valérie; Tylski, Perrine; Homyrda, Laurence; Walker, Francine; Barranger, Emmanuel; Hindié, Elif

2012-11-01

Our aims were to assess the feasibility of imaging hypoxia in cervical carcinoma with (18)F-fluoroerythronitroimidazole ((18)F-FETNIM) and to compare (18)F-FETNIM uptake with metabolic uptake of (18)F-FDG. We included 16 patients with cervical carcinoma. After imaging with FDG, (18)F-FETNIM PET/CT was performed and tumor-to-muscle (T/M) ratio uptake was assessed. (18)F- FETNIM uptake was correlated to FDG uptake and osteopontin (OPN), a marker of hypoxia, and patients' outcomes. All tumors were detected by (18)F-FDG PET. (18)F-FETNIM T/M ratios ranged from 1.3 to 5.4. There was no significant correlation between (18)F-FETNIM and (18)F-FDG uptake. High (18)F-FETNIM uptake (T/M > 3.2) was associated with reduced progression-free survival (log-rank = 0.002) and overall survival (log-rank = 0.02). Osteopontin ranged from 39 to 662 μg/L (median, 102.5 μg/L). Patients with OPN greater than 144 μg/L had reduced progression-free survival compared with those with OPN less than 144 μg/L (log-rank = 0.03). We found no significant correlation between (18)F-FETNIM uptake and OPN blood levels. Our preliminary results showed that a high uptake of (18)F-FETNIM was associated with a worse progression-free and overall survival.

Long-term behaviour of heat-resistant steels and high-temperature materials

International Nuclear Information System (INIS)

1987-01-01

This book contains 10 lectures with the following subjects: On the effect of thermal pretreatment on the structure and creep behaviour of the alloy 800 H (V. Guttmann, J. Timm); Material properties of heat resistant ferritic and austenitic steels after cold forming (W. Bendick, H. Weber); Investigations for judging the working behaviour of components made of alloy 800 and alloy 617 under creep stress (H.J. Penkalla, F. Schubert); Creep behaviour of gas turbine materials in hot gas (K.H. Kloos et al.); Effect of small cold forming on the creep beahviour of gas turbine blades made of Nimonic 90 (K.H. Keienburg et al.); Investigations on creep fatigue alternating load strength of nickel alloys (G. Raule); Change of structure, creep fatigue behaviour and life of X20 Cr Mo V 12 1 (by G. Eggeler et al.); Investigations on thermal fatigue behaviour (K.H. Mayer et al.); Creep behaviour of similar welds of the steels 13 Cr Mo 4 4, 14 MoV 6 3, 10 Cr Mo 910 and GS-17 Cr Mo V 5 11 (K. Niel et al.); Determining the creep crack behaviour of heat resistant steels with samples of different geometry (K. Maile, R. Tscheuschner). (orig.,/MM) [de

[18F]FDG PET/CT outperforms [18F]FDG PET/MRI in differentiated thyroid cancer

International Nuclear Information System (INIS)

Vrachimis, Alexis; Wenning, Christian; Weckesser, Matthias; Stegger, Lars; Burg, Matthias Christian; Allkemper, Thomas; Schaefers, Michael

2016-01-01

To evaluate the diagnostic potential of PET/MRI with [ 18 F]FDG in comparison to PET/CT in patients with differentiated thyroid cancer suspected or known to have dedifferentiated. The study included 31 thyroidectomized and remnant-ablated patients who underwent a scheduled [ 18 F]FDG PET/CT scan and were then enrolled for a PET/MRI scan of the neck and thorax. The datasets (PET/CT, PET/MRI) were rated regarding lesion count, conspicuity, diameter and characterization. Standardized uptake values were determined for all [ 18 F]FDG-positive lesions. Histology, cytology, and examinations before and after treatment served as the standards of reference. Of 26 patients with a dedifferentiated tumour burden, 25 were correctly identified by both [ 18 F]FDG PET/CT and PET/MRI. Detection rates by PET/CT and PET/MRI were 97 % (113 of 116 lesions) and 85 % (99 of 113 lesions) for malignant lesions, and 100 % (48 of 48 lesions) and 77 % (37 of 48 lesions) for benign lesions, respectively. Lesion conspicuity was higher on PET/CT for both malignant and benign pulmonary lesions and in the overall rating for malignant lesions (p < 0.001). There was a difference between PET/CT and PET/MRI in overall evaluation of malignant lesions (p < 0.01) and detection of pulmonary metastases (p < 0.001). Surgical evaluation revealed three malignant lesions missed by both modalities. PET/MRI additionally failed to detect 14 pulmonary metastases and 11 benign lesions. In patients with thyroid cancer and suspected or known dedifferentiation, [ 18 F]FDG PET/MRI was inferior to low-dose [ 18 F]FDG PET/CT for the assessment of pulmonary status. However, for the assessment of cervical status, [ 18 F]FDG PET/MRI was equal to contrast-enhanced neck [ 18 F]FDG PET/CT. Therefore, [ 18 F]FDG PET/MRI combined with a low-dose CT scan of the thorax may provide an imaging solution when high-quality imaging is needed and high-energy CT is undesirable or the use of a contrast agent is contraindicated. (orig.)

Labelling of leucocytes with 18 F-FDG

International Nuclear Information System (INIS)

Tomas, M.B.; Tronco, G.G.; Palestro, C.J.

2003-01-01

Full text: Objective: To investigate the effect of blood glucose levels on in-vitro 18 F-FDG labeling of autologous leucocytes. Methods: Seventeen volunteers, 11 men and 6 women, 20 - 54 years old, participated in this study. Using standard techniques, a mixed leucocyte suspension was prepared from 40 ml of blood withdrawn from each volunteer. Blood glucose levels were also measured for each blood sample. After resuspension in 3 ml heparinized saline, the leucocytes were incubated with 11.03 (± 4.48) mCi 18 F-FDG for 30 minutes at 370 C. The labeled cell suspension was then centrifuged for 5 min (150 g). Activity in the cell pellet and supernatant were measured and labelling efficiency calculated. Results: Blood glucose levels ranged from 80 to 178 mg% with a mean of 113 mg%. The overall labelling efficiency was 61.2% (±7.3%). The mean labelling efficiency for blood glucose levels 100 mg%. There is no statistically significant difference between the labeling efficiencies obtained at blood glucose levels 100 mg% (p =0.72). Blood Glucose Level (mg%) Labelling Efficiency (%) 100 61. Conclusion: In summary, no correlation between blood glucose levels and labeling efficiency was observed. Blood glucose levels up to 178 mg% do not affect 18 F-FDG in-vitro labelling of autologous leucocytes. (author)

Creep characterization of type 316LN and HT-9 stainless steels by the K-R creep damage model

International Nuclear Information System (INIS)

Kim, Woo Gon; Kim, Sung Ho; Ryu, Woo Seog

2001-01-01

The Kachanov and Rabotnov (K-R) creep damage model was interpreted and applied to type 316LN and HT-9 stainless steels. Seven creep constants of the model, A, B, k, m, λ, γ, and q were determined for type 316LN stainless steel. In order to quantify a damage parameter, the cavity was interruptedly traced during creep for measuring cavity area to be reflected into the damage equation. For type 316LN stainless steel, λ=ε R /ε * and λ f =ε/ε R were 3.1 and increased with creep strain. The creep curve with λ=3.1 depicted well the experimental data to the full lifetime and its damage curve showed a good agreement when γ=24. However for the HT-9 stainless steel, the values of λ and λ f were different as λ=6.2 and λ f =8.5, and their K-R creep curves did not agree with the experimental data. This mismatch in the HT-9 steel was due to the ductile fracture by softening of materials rather than the brittle fracture by cavity growth. The differences of the values in the above steels were attributed to creep ductilities at the secondary and the tertiary creep stages

A comparison of [/sup 18/F]spiroperidol, [/sup 18/F]benperidol and [/sup 18/F] haloperidol kinetics in baboon brain

International Nuclear Information System (INIS)

Arnett, C.D.; Shiue, C.Y.; Wolf, A.P.; Fowler, J.S.; Logan, J.

1984-01-01

Neuroleptic receptor ligands, spiroperidol, benperidol and haloperidol were labeled with fluorine-18 by a nucleophilic aromatic substitution reaction of p-nitrobenzo-nitrile with /sup 18/F/sup -/ to produce p-[/sup 18/F]fluorobenzonitrile which was converted to p-[/sup 18/F]fluoro-y-chlorobutyrophenone and then alkylated with the appropriate amine to give [/sup 18/F]spiroperidol ([/sup 18/F]SP), [/sup 18/F]benperidol ([/sup 18/F]BEN), or [/sup 18/F]haloperidol ([/sup 18/F]HAL). Specific activity ranged from 3 to 6 Ci/μmol. Anesthetized baboons were injected with 6-17 mCi of [/sup 18/F]-labeled tracer. Kinetic curves (striatum and cerebellum) were obtained from PETT scans up to 4 hr with each drug; [/sup 18/F]SP was studied to 8 hr. [/sup 18/F]SP and [/sup 18/F]BEN exhibited similar kinetics in striatum, with radioactivity concentration plateauing by 30 min after injection and remaining constant for the remainder of the study. These two compounds cleared rapidly from the cerebellum. [/sup 18/F]HAL showed a much different kinetic pattern in the striatum. Although it reached a higher striatal concentration (≅0.07% per ml vs. ≅ 0.02% per ml for [/sup 18/F]SP or [/sup 18/F]BEN), a peak occurred at 30 min after injection, followed by a decline almost as rapid as that in the cerebellum. Plasma analyses for [/sup 18/F]SP showed > 90% unchanged drug up to 5 min and ≅ 30% metabolites at 20 min after injection. Pretreatment with (+)-butaclamol abolished the selective distribution of [/sup 18/F]SP to the striatum in the four animals studied. Both [/sup 18/F]SP and [/sup 18/F]BEN may be suitable for PETT studies of neuroleptic receptors, but the in vivo kinetics of these compounds are markedly different from their in vitro receptor binding kinetics

Integration of G protein α (Gα) signaling by the regulator of G protein signaling 14 (RGS14).

Science.gov (United States)

Brown, Nicole E; Goswami, Devrishi; Branch, Mary Rose; Ramineni, Suneela; Ortlund, Eric A; Griffin, Patrick R; Hepler, John R

2015-04-03

RGS14 contains distinct binding sites for both active (GTP-bound) and inactive (GDP-bound) forms of Gα subunits. The N-terminal regulator of G protein signaling (RGS) domain binds active Gαi/o-GTP, whereas the C-terminal G protein regulatory (GPR) motif binds inactive Gαi1/3-GDP. The molecular basis for how RGS14 binds different activation states of Gα proteins to integrate G protein signaling is unknown. Here we explored the intramolecular communication between the GPR motif and the RGS domain upon G protein binding and examined whether RGS14 can functionally interact with two distinct forms of Gα subunits simultaneously. Using complementary cellular and biochemical approaches, we demonstrate that RGS14 forms a stable complex with inactive Gαi1-GDP at the plasma membrane and that free cytosolic RGS14 is recruited to the plasma membrane by activated Gαo-AlF4(-). Bioluminescence resonance energy transfer studies showed that RGS14 adopts different conformations in live cells when bound to Gα in different activation states. Hydrogen/deuterium exchange mass spectrometry revealed that RGS14 is a very dynamic protein that undergoes allosteric conformational changes when inactive Gαi1-GDP binds the GPR motif. Pure RGS14 forms a ternary complex with Gαo-AlF4(-) and an AlF4(-)-insensitive mutant (G42R) of Gαi1-GDP, as observed by size exclusion chromatography and differential hydrogen/deuterium exchange. Finally, a preformed RGS14·Gαi1-GDP complex exhibits full capacity to stimulate the GTPase activity of Gαo-GTP, demonstrating that RGS14 can functionally engage two distinct forms of Gα subunits simultaneously. Based on these findings, we propose a working model for how RGS14 integrates multiple G protein signals in host CA2 hippocampal neurons to modulate synaptic plasticity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Effect of a high heat flux on the corrosion of 2 1/4 Cr-1 Mo steel in superheated steam

International Nuclear Information System (INIS)

Griess, J.C.; DeVan, J.H.; Maxwell, W.A.

1977-01-01

A series of corrosion tests was conducted to determine the effect of heat flux on the corrosion of 2 1 / 4 Cr-1 Mo steel in superheated steam. The tests were conducted with a constant heat flux of (126 kW/m 2 ) 40,000 Btu hr -1 ft -2 and surface temperatures varying from 950 to 1000 0 F (510 to 541 0 C) on each specimen. Specimens were exposed for varying lengths of time, ranging from 500 to 6000 hr. Essentially all the corrosion product oxide remained on the steel during the first 2000 hr, but after that time, exfoliation of the oxide began. The percentage of corrosion product oxide lost from the specimen increased with exposure time; about 33 percent was missing after 6000 hr. After an initial period of rapid corrosion, the average corrosion rate was constant at 1.8 mils/year (45 μm/year). In contrast, isothermal specimens exposed to superheated steam at 930 0 F (499 0 C) in the same test facility corroded at a decreasing rate throughout the test. Metallographic sections showed that, with heat transfer across the specimen-steam interface, both cracks and porosity developed in the oxide, even on short exposure, a face that was undoubtedly responsible for the early exfoliation of the oxide and the constant corrosion rate

Cranberry extract inhibits in vitro adhesion of F4 and F18+Escherichia coli to pig intestinal epithelium and reduces in vivo excretion of pigs orally challenged with F18+ verotoxigenic E. coli.

Science.gov (United States)

Coddens, Annelies; Loos, Michaela; Vanrompay, Daisy; Remon, Jean Paul; Cox, Eric

2017-04-01

F4 + E. coli and F18 + E. coli infections are an important threat for pig industry worldwide. Antibiotics are commonly used to treat infected piglets, but the emerging development of resistance against antibiotics raises major concerns. Hence, alternative therapies to prevent pigs from F4 + E. coli and F18 + E. coli infections need to be developed. Since cranberry previously showed anti-adhesive activity against uropathogenic E. coli, we aimed to investigate whether cranberry extract could also inhibit binding of F4 + E. coli and F18 + E. coli to pig intestinal epithelium. Using the in vitro villus adhesion assay, we found that low concentrations of cranberry extract (20μg or 100μg/ml) have strong inhibitory activity on F4 + E. coli (75.3%, S.D.=9.31 or 95.8%, S.D.=2.56, respectively) and F18 + E. coli adherence (100% inhibition). This effect was not due to antimicrobial activity. Moreover, cranberry extract (10mg or 100mg) could also abolish in vivo binding of F4 and F18 fimbriae to the pig intestinal epithelium in ligated loop experiments. Finally, two challenge experiments with F18 + E. coli were performed to address the efficacy of in-feed or water supplemented cranberry extract. No effect could be observed in piglets that received cranberry extract only in feed (1g/kg or 10g/kg). However, supplementation of feed (10g/kg) and drinking water (1g/L) significantly decreased excretion and diarrhea. The decreased infection resulted in a decreased serum antibody response indicating reduced exposure to F18 + E. coli. Copyright © 2017 Elsevier B.V. All rights reserved.

Grazing incidence synchrotron X-ray diffraction and Moessbauer spectroscopy analyses of plasma nitrided ASTM F138 stainless steel

Energy Technology Data Exchange (ETDEWEB)

Souza, Danilo Olzon Dionysio de; Ardisson, Jose Domingos, E-mail: dolzon@gmail.com [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Silva, Edilaine Honorio [Studiecentrum voor Kernenergie (Belgium); Olzon-Dionysio, Maristela; Souza, Sylvio Dionysio de; Fabris, Jose Domingos [Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, MG (Brazil); Martinez, L.G. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2016-07-01

Full text: systematic investigation of samples of plasma-nitriding austenitic stainless steels ASTM F138 and AISI 316L is reported. The surface treatment of the steels through plasma-nitriding was used to improve further the hardness, wear and corrosion resistance of these stainless steels. The resulting layered crystallographic structure actually corresponds to several phases with close cell parameters, making their identification and quantification a real experimental challenge. The ASTM F138 and AISI 316L stainless steel disks were plasma nitrided for 4 h at 400 deg C in a 80% H{sub 2} -20% N2 atmosphere at 6 torr, using plasma current frequencies between 6 and 100 kHz. Data of Moessbauer (CEMS and CXMS) and grazing incidence synchrotron X-ray diffraction (XRD-SR) were systematically collected. The nitrided layer thickness were not in general influenced by the plasma frequency, except at 12 kHz, which produced a layer thickness of approximately 8.0 mm, being in average 40% thicker than for the other samples. CXMS and CEMS Moessbauer spectra for this 12 kHz-sample show a much more pronounced magnetic resonance lines than for the other samples. The Fe{sub 4}N phase presents a single magnetic hyperfine interaction; the other two (Fe{sub 2-3}N and the expanded austenite) present both paramagnetic and magnetic components, even though their hyperfine parameters may not be safely separated. We also present the results of XRD-SR that were probed at several depths. The data from these techniques may be consistently correlated and this leads to an improved model to explain the structure of the nitrided layers. (author)

An improved synthesis of 4-[{sup 18}F]-ADAM, a potent serotonin transporter imaging agent

Energy Technology Data Exchange (ETDEWEB)

Huang, Y.-Y. [PET Center, Department of Nuclear Medicine, Tri-Service General Hospital 325 Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan (China); Department of Biomedical Engineering and Environmental Sciences, National Thising Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China); Huang, W.-S. [PET Center, Department of Nuclear Medicine, Tri-Service General Hospital 325 Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan (China); Chu, T.-C. [Department of Biomedical Engineering and Environmental Sciences, National Thising Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China); Shiue, C.-Y. [PET Center, Department of Nuclear Medicine, Tri-Service General Hospital 325 Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan (China)], E-mail: shiue@ndmctsgh.edu.tw

2009-06-15

An improved synthesis of N,N-dimethyl-2-(2-amino-4-[{sup 18}F]fluorophenylthio)benzylamine (4-[{sup 18}F]-ADAM, 2) as a potent serotonin transporter (SERT) imaging agent is described. Molecular orbital (MO) calculation predicts that N,N-dimethyl-2- (2-nitro-4-trimethylammoniumtrifluoromethanesulfonylphenylthio)benzamide (8) is probably a better precursor than N,N-dimethyl-2-(2,4-dinitrophenylthio)benzylamine (1) for preparing 2. Radioligand 2 was synthesized by the reaction of either precursor 1 or precursor 8 with K[{sup 18}F]/K{sub 2.2.2} at 120 deg. C followed by reduction with BH{sub 3} at 80 deg. C. The radiochemical yield (EOB) of 2 synthesized from precursor 1 and 8 was 5.7{+-}2.4% (n=6) and 14.8{+-}4.0% (n=5), respectively, in a synthesis time of 120 min from EOB. The specific activity of 2 was 3 Ci/{mu}mol or 111 GBq/{mu}mol (EOB). Thus, this new synthetic method has significantly improved the radiochemical yield of 4-[{sup 18}F]-ADAM and makes this radioligand more accessible to PET Centers without a cyclotron.

Fatigue damage evolution of cold-worked austenitic nickel-free high-nitrogen steel X13CrMnMoN18-14-3 (1.4452)

Energy Technology Data Exchange (ETDEWEB)

Tikhovskiy, I.; Weiss, S.; Fischer, A. [Univ. of Duisburg-Essen, Materials Science and Engineering II, Duisburg (Germany)

2004-07-01

Due to the fact that the risk of Ni-allergies becomes more and more important for modern therapies, the necessity of Ni-free implant materials becomes increasingly important. Beside Co- and Ti-base alloys Ni-free high-nitrogen steels may offer an attractive alternative. The present work presents the austenitic high-nitrogen and nickel-free steel X13CrMnMoN18-14-3, (Material No.: 1.4452) after 20% cold-working. In addition this material was deformed under axial cyclic total strain controlled fatigue tests at room temperature. The development of dislocation structure due to different loading amplitudes was compared to none cyclically deformed material. The good mechanical und fatigue properties of these austenitic high-nitrogen steels as well as the better tribological, chemical and biological properties compared to CrNiMo-steels qualify these steels as a promising alternative in medical applications. (orig.)

Long-circulating liposomes radiolabeled with [18F]fluorodipalmitin ([18F]FDP)

International Nuclear Information System (INIS)

Marik, Jan; Tartis, Michaelann S.; Zhang, Hua; Fung, Jennifer Y.; Kheirolomoom, Azadeh; Sutcliffe, Julie L.; Ferrara, Katherine W.

2007-01-01

Synthesis of a radiolabeled diglyceride, 3-[ 18 F]fluoro-1,2-dipalmitoylglycerol [[ 18 F]fluorodipalmitin ([ 18 F]FDP)], and its potential as a reagent for radiolabeling long-circulating liposomes were investigated. The incorporation of 18 F into the lipid molecule was accomplished by nucleophilic substitution of the p-toluenesulfonyl moiety with a decay-corrected yield of 43±10% (n=12). Radiolabeled, long-circulating polyethylene-glycol-coated liposomes were prepared using a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethyleneglycol)-2000] ammonium salt (61:30:9) and [ 18 F]FDP with a decay-corrected yield of 70±8% (n=4). PET imaging and biodistribution studies were performed with free [ 18 F]FDP and liposome-incorporated [ 18 F]FDP. Freely injected [ 18 F]FDP had the highest uptake in the liver, spleen and lungs. Liposomal [ 18 F]FDP remained in blood circulation at near-constant levels for at least 90 min, with a peak concentration near 2.5%ID/cc. Since [ 18 F]FDP was incorporated into the phospholipid bilayer, it could potentially be used for radiolabeling a variety of lipid-based drug carriers

Influence of P-Glycoprotein Inhibition or Deficiency at the Blood-Brain Barrier on (18)F-2-Fluoro-2-Deoxy-D-glucose ( (18)F-FDG) Brain Kinetics.

Science.gov (United States)

Tournier, Nicolas; Saba, Wadad; Goutal, Sébastien; Gervais, Philippe; Valette, Héric; Scherrmann, Jean-Michel; Bottlaender, Michel; Cisternino, Salvatore

2015-05-01

The fluorinated D-glucose analog (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) is the most prevalent radiopharmaceutical for positron emission tomography (PET) imaging. P-Glycoprotein's (P-gp, MDR1, and ABCB1) function in various cancer cell lines and tumors was shown to impact (18)F-FDG incorporation, suggesting that P-gp function at the blood-brain barrier may also modulate (18)F-FDG brain kinetics. We tested the influence of P-gp inhibition using the cyclosporine analog valspodar (PSC833; 5 μM) on the uptake of (18)F-FDG in standardized human P-gp-overexpressing cells (MDCKII-MDR1). Consequences for (18)F-FDG brain kinetics were then assessed using (i) (18)F-FDG PET imaging and suitable kinetic modelling in baboons without or with P-gp inhibition by intravenous cyclosporine infusion (15 mg kg(-1) h(-1)) and (ii) in situ brain perfusion in wild-type and P-gp/Bcrp (breast cancer resistance protein) knockout mice and controlled D-glucose exposure to the brain. In vitro, the time course of (18)F-FDG uptake in MDR1 cells was influenced by the presence of valspodar in the absence of D-glucose but not in the presence of high D-glucose concentration. PET analysis revealed that P-gp inhibition had no significant impact on estimated brain kinetics parameters K 1, k 2, k 3, V T , and CMRGlc. The lack of P-gp effect on in vivo (18)F-FDG brain distribution was confirmed in P-gp/Bcrp-deficient mice. P-gp inhibition indirectly modulates (18)F-FDG uptake into P-gp-overexpressing cells, possibly through differences in the energetic cell level state. (18)F-FDG is not a P-gp substrate at the BBB and (18)F-FDG brain kinetics as well as estimated brain glucose metabolism are influenced by neither P-gp inhibition nor P-gp/Bcrp deficiencies in baboon and mice, respectively.

The 18F-labelled alkylating agent 2,2,2-trifluoroethyl triflate: synthesis and specific activity

International Nuclear Information System (INIS)

Johnstroem, P.; Stone-Elander, S.

1995-01-01

A method for synthesizing the alkylating agent 2,2,2-trifluoroethyl triflate labelled with [ 18 ]fluoride in the two position is presented. Ethyl [2- 18 )F]-trifluoroacetate was synthesized by the nucleophilic reaction of [ 18 F]F - with ethyl bromodifluoroacetate in DMSO (45-60%, 5 min, 80 o C) and subsequently converted to [2- 18 F]-2,2,2-trifluoroethanol using alane in THF (85-95%, 2 min, 40 o C. Reaction with triflic anhydride in 2,6-lutidine produced [2- 18 F]-2,2,2-trifluoroethyl triflate (70-80%, 1 min, 0 o C. In all three cases the product was removed from the reaction vessel by heating to distil under a stream of nitrogen. [2- 18 F]-2,2,2-Trifluoroethyl triflate was used to label 2-oxoquazepam by N-alkylation in a toulene:DMF mixture (80-85%, 20 min, 120 o C). Although no-carrier-added [ 18 )F]F - was used, considerable unlabelled ethyl trifluoroacetate was produced in the first reaction. Varying the conditions for the fluoro-debromination reaction did not appreciably improve the relative ratio of labelled to unlabelled ester. The specific activity of the labelled 1,4-benzodiazepine-2-one obtained from 1850 MBq [ 18 F]F - was found to be ≅37 MBq/μmol (1mCi/μmol). (Author)

1-[[sup 18]F]fluoro-2-propanol p-toluenesulfonate: a synthon for the preparation of N-([[sup 18]F]fluoroisopropyl)amines

Energy Technology Data Exchange (ETDEWEB)

Groot, T.J. de; Elsinga, P.H.; Visser, G.M.; Vaalburg, W. (Groningen Univ. (Netherlands). PET Center and GCCS)

1992-11-01

The new radiochemical synthon 1-[[sup 18]F]fluoro-2-propanol p-toluenesulfonate is prepared with a radiochemical yield of 45% [corrected for decay to beginning of synthesis, synthesis time 40 min]. This compound is used to prepare the [[sup 18]F]fluoroisopropyl-alkylated derivatives of benzylamine and norephedrine with a yield of 7 and 2% respectively, (synthesis time 90 min). This alkylation reaction a good perspective for the preparation of [[sup 18]F]fluoro-labelled analogues of [beta][sub 1]-adrenergic receptor binding ligands for PET. (Author).

Comparisons of [{sup 18}F]-1-deoxy-1-fluoro-scyllo-inositol with [{sup 18}F]-FDG for PET imaging of inflammation, breast and brain cancer xenografts in athymic mice

Energy Technology Data Exchange (ETDEWEB)

McLarty, Kristin; Moran, Matthew D. [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Scollard, Deborah A.; Chan, Conrad [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Sabha, Nesrin; Mukherjee, Joydeep; Guha, Abhijit [Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, University of Toronto, ON, M5G 1X8 (Canada); McLaurin, JoAnne [Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, M5S 3H2 (Canada); Nitz, Mark [Department of Chemistry, University of Toronto, Toronto, ON, M5S 3H6 (Canada); Houle, Sylvain; Wilson, Alan A. [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Reilly, Raymond M., E-mail: raymond.reilly@utoronto.ca [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Toronto General Research Institute, University Health Network, Toronto, ON, M5G 2M9 (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Vasdev, Neil, E-mail: neil.vasdev@utoronto.ca [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)

2011-10-15

Introduction: The aim of the study was to evaluate the uptake of [{sup 18}F]-1-deoxy-1-fluoro-scyllo-inositol ([{sup 18}F]-scyllo-inositol) in human breast cancer (BC) and glioma xenografts, as well as in inflammatory tissue, in immunocompromised mice. Studies of [{sup 18}F]-2-fluoro-2-deoxy-D-glucose ([{sup 18}F]-FDG) under the same conditions were also performed. Methods: Radiosynthesis of [{sup 18}F]-scyllo-inositol was automated using a commercial synthesis module. Tumour, inflammation and normal tissue uptakes were evaluated by biodistribution studies and positron emission tomography (PET) imaging using [{sup 18}F]-scyllo-inositol and [{sup 18}F]-FDG in mice bearing subcutaneous MDA-MB-231, MCF-7 and MDA-MB-361 human BC xenografts, intracranial U-87 MG glioma xenografts and turpentine-induced inflammation. Results: The radiosynthesis of [{sup 18}F]-scyllo-inositol was automated with good radiochemical yields (24.6%{+-}3.3%, uncorrected for decay, 65{+-}2 min, n=5) and high specific activities ({>=}195 GBq/{mu}mol at end of synthesis). Uptake of [{sup 18}F]-scyllo-inositol was greatest in MDA-MB-231 BC tumours and was comparable to that of [{sup 18}F]-FDG (4.6{+-}0.5 vs. 5.5{+-}2.1 %ID/g, respectively; P=.40), but was marginally lower in MDA-MB-361 and MCF-7 xenografts. Uptake of [{sup 18}F]-scyllo-inositol in inflammation was lower than [{sup 18}F]-FDG. While uptake of [{sup 18}F]-scyllo-inositol in intracranial U-87 MG xenografts was significantly lower than [{sup 18}F]-FDG, the tumour-to-brain ratio was significantly higher (10.6{+-}2.5 vs. 2.1{+-}0.6; P=.001). Conclusions: Consistent with biodistribution studies, uptake of [{sup 18}F]-scyllo-inositol was successfully visualized by PET imaging in human BC and glioma xenografts, with lower accumulation in inflammatory tissue than [{sup 18}F]-FDG. The tumour-to-brain ratio of [{sup 18}F]-scyllo-inositol was also significantly higher than that of [{sup 18}F]-FDG for visualizing intracranial glioma xenografts in

Preclinical Evaluation of 18F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by Immuno-PET.

Science.gov (United States)

Vaidyanathan, Ganesan; McDougald, Darryl; Choi, Jaeyeon; Koumarianou, Eftychia; Weitzel, Douglas; Osada, Takuya; Lyerly, H Kim; Zalutsky, Michael R

2016-06-01

The human growth factor receptor type 2 (HER2) is overexpressed in breast as well as other types of cancer. Immuno-PET, a noninvasive imaging procedure that could assess HER2 status in both primary and metastatic lesions simultaneously, could be a valuable tool for optimizing application of HER2-targeted therapies in individual patients. Herein, we have evaluated the tumor-targeting potential of the 5F7 anti-HER2 Nanobody (single-domain antibody fragment; ∼13 kDa) after (18)F labeling by 2 methods. The 5F7 Nanobody was labeled with (18)F using the novel residualizing label N-succinimidyl 3-((4-(4-(18)F-fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ((18)F-SFBTMGMB; (18)F-RL-I) and also via the most commonly used (18)F protein-labeling prosthetic agent N-succinimidyl 3-(18)F-fluorobenzoate ((18)F-SFB). For comparison, 5F7 Nanobody was also labeled using the residualizing radioiodination agent N-succinimidyl 4-guanidinomethyl-3-(125)I-iodobenzoate ((125)I-SGMIB). Paired-label ((18)F/(125)I) internalization assays and biodistribution studies were performed on HER2-expressing BT474M1 breast carcinoma cells and in mice with BT474M1 subcutaneous xenografts, respectively. Small-animal PET/CT imaging of 5F7 Nanobody labeled using (18)F-RL-I also was performed. Internalization assays indicated that intracellularly retained radioactivity for (18)F-RL-I-5F7 was similar to that for coincubated (125)I-SGMIB-5F7, whereas that for (18)F-SFB-5F7 was lower than coincubated (125)I-SGMIB-5F7 and decreased with time. BT474M1 tumor uptake of (18)F-RL-I-5F7 was 28.97 ± 3.88 percentage injected dose per gram of tissue (%ID/g) at 1 h and 36.28 ± 14.10 %ID/g at 2 h, reduced by more than 90% on blocking with trastuzumab, indicating HER2 specificity of uptake, and was also 26%-28% higher (P < 0.05) than that of (18)F-SFB-5F7. At 2 h, the tumor-to-blood ratio for (18)F-RL-I-5F7 (47.4 ± 13.1) was significantly higher (P < 0.05) than for (18)F-SFB-5F7 (25.4 ± 10

Radiation induced microstructural evolution in ferritic/martensitic steels

International Nuclear Information System (INIS)

Kohno, Y.; Kohyama, A.; Asakura, K.; Gelles, D.S.

1993-01-01

R and D of ferritic/martensitic steels as structural materials for fusion reactor is one of the most important issues of fusion technology. The efforts to characterize microstructural evolution under irradiation in the conventional Fe-Cr-Mo steels as well as newly developed Fe-Cr-Mn or Fe-Cr-W low activation ferritic/ martensitic steels have been continued. This paper provides some of the recent results of heavy irradiation effects on the microstructural evolution of ferritic/martensitic steels neutron irradiated in the FFTF/MOTA (Fast Flux Test Facility/Materials Open Test Assembly). Materials examined are Fe-10Cr-2Mo dual phase steel (JFMS: Japanese Ferritic/Martensitic Steel), Fe-12Cr-XMn-1Mo manganese stabilized martensitic steels and Fe-8Cr-2W Tungsten stabilized low activation martensitic steel (F82H). JFMS showed excellent void swelling resistance similar to 12Cr martensitic steel such as HT-9, while the manganese stabilized steels and F82H showed less void swelling resistance with small amount of void swelling at 640-700 K (F82H: 0.14% at 678 K). As for irradiation response of precipitate behavior, significant formation of intermetallic χ phase was observed in the manganese stabilized steels along grain boundaries which is though to cause mechanical property degradation. On the other hand, precipitates identified were the same type as those in unirradiated condition in F82H with no recognition of irradiation induced precipitates, which suggested satisfactory mechanical properties of F82H after the irradiation. (author)

Visualization of acute liver damage induced by cycloheximide in rats using PET with [(18F]FEDAC, a radiotracer for translocator protein (18 kDa.

Directory of Open Access Journals (Sweden)

Akiko Hatori

Full Text Available Liver damage induced by drug toxicity is an important concern for both medical doctors and patients. The aim of this study was to noninvasively visualize acute liver damage using positron emission tomography (PET with N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-[(18F]fluoroethyl-8-oxo-2-phenyl-9H-purin-9-yl]acetamide ([(18F]FEDAC, a radiotracer specific for translocator protein (18 kDa, TSPO as a biomarker for inflammation, and to determine cellular sources enriching TSPO expression in the liver. A mild acute liver damage model was prepared by a single intraperitoneal injection of cycloheximide (CHX into rats. Treatment with CHX induced apoptosis and necrotic changes in hepatocytes with slight neutrophil infiltration. The uptake of radioactivity in the rat livers was measured with PET after injection of [(18F]FEDAC. The uptake of [(18F]FEDAC increased in livers damaged from treatment with CHX compared to the controls. Presence of TSPO was examined in the liver tissue using quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical assays. mRNA expression of TSPO was elevated in the damaged livers compared to the controls, and the level was correlated with the [(18F]FEDAC uptake and severity of damage. TSPO expression in the damaged liver sections was mainly found in macrophages (Kupffer cells and neutrophils, but not in hepatocytes. The elevation of TSPO mRNA expression was derived from the increase of the number of macrophages with TSPO and neutrophils with TSPO in damaged livers. From this study we considered that PET imaging with [(18F]FEDAC represented the mild liver damage through the enhanced TSPO signal in inflammatory cells. We conclude that this method may be a useful tool for diagnosis in early stage of acute liver damage.

Comparative studies of epibatidine derivatives [{sup 18}F]NFEP and [{sup 18}F]N-Methyl-NFEP: kinetics, nicotine effect, and toxicity

Energy Technology Data Exchange (ETDEWEB)

Ding Yushin E-mail: ding@bnl.gov; Molina, Patricia E.; Fowler, Joanna S.; Logan, Jean; Volkow, Nora D.; Kuhar, Michael J.; Carroll, F. Ivy

1999-01-01

We have previously shown that [{sup 18}F]norchlorofluoroepibatidine ([{sup 18}F]NFEP) would be an ideal radiotracer for positron emission tomography (PET) imaging of nicotinic acetylcholine receptors (nAChR); however, its high toxicity is a limiting factor for human studies. We, therefore, synthesized its N-methyl derivative ([{sup 18}F]N-Me-NFEP) and carried out comparative studies. The distribution volumes for different brain regions were higher for [{sup 18}F]N-Me-NFEP than those for [{sup 18}F]NFEP (average: 52.5 {+-} 0.9 vs. 36.4 {+-} 0.7 for thalamus), though the distribution volume (DV) ratios were similar (3.93 {+-} 0.27 vs. 3.65 {+-} 0.19 for thalamus to cerebellum). Treatment with nicotine reduced the binding of both radiotracers. Toxicology studies in awake rats showed that N-methyl-NFEP has a lower mortality (0 vs. 30%) and smaller effect on plasma catecholamines than NFEP at a dose of 1.5 {mu}g/kg. However, marked alterations in cardiorespiratory parameters were observed after injection of N-methyl-NFEP (0.5 {mu}g/kg, IV) to an awake dog. methresults suggest that although the binding characteristics of [{sup 18}F]NFEP and [{sup 18}F]N-Me-NFEP appear to be ideally suited for PET imaging studies of the human brain, their relatively small safety margin will limit their use in humans.

Predominant contribution of L-type amino acid transporter to 4-borono-2-18F-fluoro-phenylalanine uptake in human glioblastoma cells

International Nuclear Information System (INIS)

Yoshimoto, Mitsuyoshi; Kurihara, Hiroaki; Honda, Natsuki; Kawai, Keiichi; Ohe, Kazuyo; Fujii, Hirofumi; Itami, Jun; Arai, Yasuaki

2013-01-01

Introduction: 4-Borono-2- 18 F-fluoro-phenylalanine ( 18 F-FBPA) has been used to anticipate the therapeutic effects of boron neutron capture therapy (BNCT) with 4-borono-L-phenylalanine (BPA). Similarly, L-[methyl- 11 C]-methionine ( 11 C-MET), the most popular amino acid PET tracer, is a possible candidate for this purpose. We investigated the transport mechanism of 18 F-FBPA and compared it with that of 14 C-MET in human glioblastoma cell lines. Methods: Uptake of 18 F-FBPA and 14 C-MET was examined in A172, T98G, and U-87MG cells using 2-aminobicyclo-(2.2.1)-heptane-2-carboxylic acid (a system L-specific substrate), 2-(methylamino)-isobutyric acid (a system A-specific substrate), and BPA. Gene expression was analyzed by quantitative real time polymerase chain reaction. Results: System L was mainly involved in the uptake of 18 F-FBPA (74.5%–81.1% of total uptake) and 14 C-MET (48.3%–59.4%). System A and ASC also contributed to the uptake of 14 C-MET. Inhibition experiments revealed that BPA significantly decreased the uptake of 18 F-FBPA, whereas 31%–42% of total 14 C-MET uptake was transported by BPA non-sensitive transporters. In addition, 18 F-FBPA uptake correlated with LAT1 and total LAT expressions. Conclusion: This study demonstrated that 18 F-FBPA was predominantly transported by system L in human glioblastoma cells compared to 14 C-MET. Although further studies are needed to elucidate the correlation between 18 F-FBPA uptake and BPA content in tumor tissues, 18 F-FBPA is suitable for the selection of patients who benefit from BNCT with BPA

Early static {sup 18}F-FET-PET scans have a higher accuracy for glioma grading than the standard 20-40 min scans

Energy Technology Data Exchange (ETDEWEB)

Albert, Nathalie L.; Winkelmann, Isabel; Wenter, Vera; Mille, Erik; Todica, Andrei; Brendel, Matthias; Bartenstein, Peter [Ludwig-Maximilians-University Munich, Department of Nuclear Medicine, Munich (Germany); Suchorska, Bogdana; Tonn, Joerg-Christian [Ludwig-Maximilians-University Munich, Department of Neurosurgery, Munich (Germany); Schmid-Tannwald, Christine [Ludwig-Maximilians-University Munich, Institute for Clinical Radiology, Munich (Germany); La Fougere, Christian [University of Tuebingen, Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, Tuebingen (Germany)

2016-06-15

Current guidelines for glioma imaging by positron emission tomography (PET) using the amino acid analogue O-(2-[{sup 18}F]fluoroethyl)-L-tyrosine ({sup 18}F-FET) recommend image acquisition from 20-40 min post injection (p.i.). The maximal tumour-to-background evaluation (TBR{sub max}) obtained in these summation images does not enable reliable differentiation between low and high grade glioma (LGG and HGG), which, however, can be achieved by dynamic {sup 18}F-FET-PET. We investigated the accuracy of tumour grading using TBR{sub max} values at different earlier time points after tracer injection. Three hundred and fourteen patients with histologically proven primary diagnosis of glioma (131 LGG, 183 HGG) who had undergone 40-min dynamic {sup 18}F-FET-PET scans were retrospectively evaluated. TBR{sub max} was assessed in the standard 20-40 min summation images, as well as in summation images from 0-10 min, 5-15 min, 5-20 min, and 15-30 min p.i., and kinetic analysis was performed. TBR{sub max} values and kinetic analysis were correlated with histological classification. ROC analyses were performed for each time frame and sensitivity, specificity, and accuracy were assessed. TBR{sub max} values in the earlier summation images were significantly better for tumour grading (P < 0.001) when compared to standard 20-40 min scans, with best results for the early 5-15 min scan. This was due to higher TBR{sub max} in the HGG (3.9 vs. 3.3; p < 0.001), while TBR{sub max} remained nearly stable in the LGG (2.2 vs. 2.1). Overall, accuracy increased from 70 % in the 20-40 min analysis to 77 % in the 5-15 min images, but did not reach the accuracy of dynamic analysis (80 %). Early TBR{sub max} assessment (5-15 min p.i.) is more accurate for the differentiation between LGG and HGG than the standard static scan (20-40 min p.i.) mainly caused by the characteristic high {sup 18}F-FET uptake of HGG in the initial phase. Therefore, when dynamic {sup 18}F-FET-PET cannot be performed

EPR experiments in LiTbF4, LiHoF4, and LiErF4 at submillimeter frequencies

DEFF Research Database (Denmark)

Magariño, J.; Tuchendler, J.; Beauvillain, P.

1980-01-01

Electron-paramagnetic-resonance experiments in LiTbF4, LiHoF4, and LiErF4 have been performed at frequencies between 70 and 600 GHz, in magnetic fields up to 60 kG and in the temperature range 1.4......Electron-paramagnetic-resonance experiments in LiTbF4, LiHoF4, and LiErF4 have been performed at frequencies between 70 and 600 GHz, in magnetic fields up to 60 kG and in the temperature range 1.4...

Radiation and chemical stability of 2-deoxy-2-[18F]fluoro-D-glucose radiopharmaceutical

International Nuclear Information System (INIS)

Buriova, M.

2004-07-01

molecules association with formate anion HCOO - and also for negative ions of deprotonised molecules. All acids appeared in the form of their lactones. FDG and GLC exhibited tendency for formation of a mixed associate charged by HCOO - anion. On the amine bond silica gel HPTLC column, FDG is poorly separated from fluoride, which even in presence of Kryptofix 2.2.2 remains on the start like on the silica gel layer. The last parathion is to be used as a standard technique for [ 18 F]F - assay. At LC-MS Kryptofix provides a very well measurable signals of associates with NH 4 + a H + ions in positive mode of ESI MS. Sensitivity of the ESI MS detector towards sugars is for three orders of magnitude higher than the refraction index detector, which is used for routine analysis, and enables estimation of molar activity of non-carrier-added 2-[ 18 F]FDG. The results of quantitative LC/MS analysis and high-efficient radiometric detector were used for specific activity of 2-[ 18 F]FDG assessment. Concentration of FDG carrier in 2-[ 18 F]FDG preparation was found to be 6 mg.dm -3 and in combination with a radiometric detector the specific activity 6.6 GBq.μmol -1 of 2-[ 18 F]FDG was found. The molar activity of carrier-free ( 18 F)FDG is 63 TBq.μmol -1 , and for good quality of bio-specific ligands at PET it is supposed to be minimally 1 kBq.fmol -1 . Radiation and chemical stability of 2-deoxy-2-[ 18 F]fluoro-D-glucose, and its comparison with glucose at oxidation by Fenton's reagent and autoradiolysis was found. The main oxidation products of FDG and glucose by Fenton's reagent were arabonic acid at 14-23% yield, gluconic acid 12%, both glucuronic acid and arabinose at 5%. In case of FDG among the principal products 2-fluorgluconic acid and 2-fluorgluconic acid by 2.7 % and 4% yields respectively were identified. The dose rates in real solutions of 2-[ 18 F]FDG, as well as the radiation-chemical yields of radioactive (fluorinated), but also further products of autoradiolysis of 2

Comparison of prognosis values of pre therapy PET-T.D.M. with {sup 18}F-F.D.G. and MRI in the uterus cervix cancer; Comparaison des valeurs pronostiques des TEP-TDM au 18F-FDG et IRM pretherapeutiques dans le cancer du col de l'uterus

Energy Technology Data Exchange (ETDEWEB)

Chastan, M.; Baron, M.; Diologent, B.; Edet Sanson, A.; Guernou, M.; Vera, P.; Hitzel, A. [Centre Henri-Becquerel, Rouen, (France); Manrique, A. [GIP Cyceron, Caen, (France)

2009-05-15

The objective is to compare the prognosis value of the pre-therapy pelvis PET--T.D.M. with {sup 18}F-F.D.G. and MRI in the uterine cervix carcinoma. The conclusions: in the uterine cervix carcinomas, the existence of a pelvis ganglion injury on the pre-therapy PET-T.D.M. with {sup 18}F-F.D.G. is a prognosis factor independent of recurrence and death at one year. The MRI does not bring any additional information relative to the prognosis of the disease. (N.C.)

Effect of cold deformation on latent energy value and high-temperature mechanical properties of 12Cr18Ni10Ti steel

International Nuclear Information System (INIS)

Maksimkin, O.P.; Shiganakov, Sh.B.; Gusev, M.N.

1997-01-01

Energetic and magnetic characteristics and also the high-temperature mechanical properties depending on the preliminary cold deformation of 12Cr18Ni10Ti steel are presented. It is shown that the value of storage energy in the steel has being grown with increase of the deformation. The rate of its growth has been increased after beginning of martensitic γ→α'- transformation when value of comparative storage energy at first decreased and then has been stay practically constant. Level of mechanical properties of the steel at 1073 K has been determined not only by value of cold deformation but and structural reconstruction corresponding to deformations 35-45% and accompanying with α'-phase martensite formation and change of energy accumulating rate. Preliminary cold deformation (40-60 %) does not improve high- temperature plasticity of steel samples implanted by helium. refs. 7, figs. 2

Performances evaluation of the PET/CT with {sup 18}F-F.D.G. in the diagnosis of peritoneal carcinosis with a colorectal origin; Evaluation des performances de la TEP-TDM au {sup 18}F-FDG dans le diagnostic de la carcinose peritoneale d'origine colorectale

Energy Technology Data Exchange (ETDEWEB)

Bullier, E. [CHU de Bordeaux, Service de medecine nucleaire, hopital de Haut-Leveque, 33 (France); Bonichon, F.; Cazeau, A.L. [Institut Bergonie CRLCC d' Aquitaine, service de medecine nucleaire, 33 - Bordeaux (France); Descat, E. [Institut Bergonie CRLCC d' Aquitaine, service de radiologie, 33 - Bordeaux (France); Evrard, S. [Institut Bergonie CRLCC d' Aquitaine, Dept. de Chirurgie, 33 - Bordeaux (France); Picat, Q. [Bergonie CRLCC d' Aquitaine, Dept. de biostatistique, 33 - Bordeaux (France)

2010-07-01

Purpose: the purpose of this study is to evaluate the performances and the inter-observers concordances of the PET-CT with {sup 18}F-F.D.G. in the detection of the peritoneal carcinosis in colorectal cancers, with evaluation of peritoneal extension, description of semiotics signs allowing to raise the diagnosis and confrontation of this performance to that of CT. Conclusions: The PET-CT with {sup 18}F-F.D.G. seems to be a powerful and reproducible examination for the peritoneal carcinosis diagnosis, with a methodology of research oriented proofreading of peritoneal carcinosis. Studies are to make to evaluate prospectively the extension of peritoneal carcinosis. (N.C.)

Fluorine-18 radiopharmaceuticals beyond [18F]FDG for use in oncology and neurosciences

International Nuclear Information System (INIS)

Coenen, H.H.; Elsinga, P.H.; Iwata, R.; Kilbourn, M.R.; Pillai, M.R.A.; Rajan, M.G.R.; Wagner, H.N.; Zaknun, J.J.

2010-01-01

Positron emission tomography (PET) is a rapidly expanding clinical modality worldwide thanks to the availability of compact medical cyclotrons and automated chemistry for the production of radiopharmaceuticals. There is an armamentarium of fluorine-18 ( 18 F) tracers that can be used for PET studies in the fields of oncology and neurosciences. However, most of the 18 F-tracers other than 2-deoxy-2-[18F]fluoro-D-glucose (FDG) are in less than optimum human use and there is considerable scope to bring potentially useful 18 F-tracers to clinical investigation stage. The International Atomic Energy Agency (IAEA) convened a consultants' group meeting to review the current status of 18 F-based radiotracers and to suggest means for accelerating their use for diagnostic applications. The consultants reviewed the developments including the synthetic approaches for the preparation of 18 F-tracers for oncology and neurosciences. A selection of three groups of 18 F-tracers that are useful either in oncology or in neurosciences was done based on well-defined criteria such as application, lack of toxicity, availability of precursors and ease of synthesis. Based on the recommendations of the consultants' group meeting, IAEA started a coordinated research project on 'Development of 18 F radiopharmaceuticals (beyond [ 18 F]FDG) for use in oncology and neurosciences' in which 14 countries are participating in a 3-year collaborative program. The outcomes of the coordinated research project are expected to catalyze the wider application of several more 18 F-radiopharmaceuticals beyond FDG for diagnostic applications in oncology and neurosciences.

Direct diamond turning of steel molds for optical replication

Science.gov (United States)

Klocke, Fritz; Dambon, Olaf; Bulla, Benjamin; Heselhaus, Michael

2009-05-01

In this paper the most recent investigations in ultrasonic assisted diamond machining of hardened steel at the Fraunhofer IPT is presented. The goal of this technology is to unify the outrageous specifications of diamond machining process with steel material. The focus lies on the kinematic influence of the discrete frequencies 40 kHz and 60 kHz. Special interest is given to the reachable surface roughness depending on process parameters. The machined steel (1.2083, X40Cr14, STAVAX ESU) is a common mold die material for optical replication processes.Results of the accomplished investigations show the potential of the ultrasonic assisted process and recent developments. By increasing the frequency from 40 kHz to 60 kHz the overall process stability is increased. This makes the process less vulnerable towards feed rate variation or towards the variation of machined material hardness. Furthermore no tool wear is detected at high material removal rates or high cutting distances during component machining.

Imaging malignant melanoma with {sup 18}F-5-FPN

Energy Technology Data Exchange (ETDEWEB)

Feng, Hongyan; Xia, Xiaotian; Li, Chongjiao; Song, Yiling; Qin, Chunxia; Liu, Qingyao; Zhang, Yongxue; Lan, Xiaoli [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (China); Hubei Key Laboratory of Molecular Imaging (China)

2016-01-15

Radiolabelled benzamides are attractive candidates for targeting melanoma because they bind to melanin and exhibit high tumour uptake and retention. {sup 18}F-5-Fluoro-N-(2-[diethylamino]ethyl)picolinamide ({sup 18}F-5-FPN), a benzamide analogue, was prepared and its pharmacokinetics and binding affinity evaluated both in vitro and in vivo to assess its clinical potential in the diagnosis and staging of melanoma. {sup 18}F-5-FPN was prepared and purified. Its binding specificity was measured in vitro in two different melanoma cell lines, one pigmented (B16F10 cells) and one nonpigmented (A375m cells), and in vivo in mice xenografted with the same cell lines. Dynamic and static PET images using {sup 18}F-5-FPN were obtained in the tumour-bearing mice, and the static images were also compared with those acquired with {sup 18}F-FDG. PET imaging with {sup 18}F-5-FPN was also performed in B16F10 tumour-bearing mice with lung metastases. {sup 18}F-5-FPN was successfully prepared with radiochemical yields of 5 - 10 %. Binding of {sup 18}F-5-FPN to B16F10 cells was much higher than to A375m cells. On dynamic PET imaging B16F10 tumours were visible about 1 min after injection of the tracer, and the uptake gradually increased over time. {sup 18}F-5-FPN was rapidly excreted via the kidneys. B16F10 tumours were clearly visible on static images acquired 1 and 2 h after injection, with high uptake values of 24.34 ± 6.32 %ID/g and 16.63 ± 5.41 %ID/g, respectively, in the biodistribution study (five mice). However, there was no visible uptake by A375m tumours. {sup 18}F-5-FPN and {sup 18}F-FDG PET imaging were compared in B16F10 tumour xenografts, and the tumour-to-background ratio of {sup 18}F-5-FPN was ten times higher than that of {sup 18}F-FDG (35.22 ± 7.02 vs. 3.29 ± 0.53, five mice). {sup 18}F-5-FPN PET imaging also detected simulated lung metastases measuring 1 - 2 mm. {sup 18}F-5-FPN specifically targeted melanin in vitro and in vivo with high retention and affinity

Comparison of six methods of segmentation of tumor volume on the 18F-F.D.G. PET scan with reference histological volume in non small cell bronchopulmonary cancers

International Nuclear Information System (INIS)

Venel, Y.; Garhi, H.; Baulieu, J.L.; Prunier-Aesch, C.; Muret, A. de; Barillot, I.

2008-01-01

The 18 F-F.D.G. PET has demonstrated its importance in oncology, for initial extension and efficacy of anti tumoral therapeutics. Several studies have attempted to prove its utility to define tumoral volumes for conformational radiotherapy in non small cell lung cancers. Some authors have suggested the use of threshold of tumor intensity uptake with 40 or 50% of maximal intensity. Black et al. have determined contouring with linear regression formula of mean semi-quantitative index of tumor uptake (standard uptake value): SUV threshold = 0.307 Sub average + 0.588. Nestle et al. have taken into account the background noise intensity and mean intensity of the tumor: I threshold = β I average +I noise with β 0.15. Our study was done in collaboration with Inserm U618 team and has compared volumes defined on PET scan defined according to different methods based on intensity or S.U.V. to the tumour volume determined on CT scan by radio physicist. We have compared those volumes with histological volume that we considered for reference. Four patients have been included. They had 18 F-F.D.G. PET scan followed by complete tumoral removal surgery. Specific histological procedure allowed to define complete size of the tumor in re expanded lung. Comparatively to pathology, the volumes obtained using I max 40 and I max 50 are all underestimated. The volumes defined by Black's et al. method are under evaluated for the two largest tumours (15.8% to 22%) and overestimated for the two smallest ones (17.9 to 82.9%). Nestle's et al. method, using β = 0.15, correctly estimates two tumor volumes over 2 cm, but overestimates the two small tumors (79.6 to 124%). Finally, the corrected Nestle's et al. formula (using β = 0.264) overestimates three tumours. Volumes defined on CT scan by radio physicist are correct for one lesion, underestimated for one and overestimated for two other ones (44 and 179.5%). Nestle's et al. method seems to be the most accurate for tumours over 2 cm of

The influence of interstitial impurities on temperature ranges of deuterium retention in austenitic stainless steel 18Cr10NiTi

International Nuclear Information System (INIS)

Neklyudov, I.M.; Morozov, O.M.; Kulish, V.G.; Zhurba, V.I.; Galytsky, A.G.; Piatenko, E.V.

2009-01-01

The influence of nitrogen, oxygen and helium on the temperature range of deuterium retention in 18Cr10NiTi stainless steel (of AISI304L type) has been investigated. It is demonstrated that the introduction of oxygen, nitrogen or helium into 18Cr10NiTi steel extends the upper limit in the high-temperature range of deuterium retention. It has been found that for 18Cr10NiTi stainless steel, pre-irradiated with helium ions, the increase in the temperature range of deuterium retention occurs in steps: on attainment of helium concentration of ∼0.5 at.% He the temperature range increases by ∼100 K, and on attainment of helium concentration of ∼2.5 at.% He the temperature range increases by ∼350 K. The introduction of oxygen into 18Cr10NiTi stainless steel results in the increase of the temperature range of deuterium retention in the direction of rise in temperature. In the deuterium thermodesorption spectrum, this manifests itself by the occurrence of an additional low-amplitude peak with the maximum temperature T m ∼ 560 K. The introduction of nitric impurity into 18Cr10NiTi stainless steel results in the extension of the temperature range of deuterium retention towards higher temperatures.

Synthesis and Preliminary Evaluation of 5-[18F]fluoroleucine.

Science.gov (United States)

Chin, Bennett B; McDougald, Darryl; Weitzel, Douglas H; Hawk, Thomas; Reiman, Robert E; Zalutsky, Michael R; Vaidyanathan, Ganesan

2017-01-01

Amino acid transporters, such as LAT1, are overexpressed in aggressive prostate and breast carcinomas, directly influencing pathways of growth and proliferation. The purpose of this study was to synthesize and characterize a novel 18F labeled leucine analog, 5-[18F]fluoroleucine, as a potential imaging agent for aggressive tumors which may not be amenable to imaging by FDG PET. 5-fluoroleucine was synthesized and characterized, and its 18F-labeled analog was synthesized from a mesylate precursor. First, breast cancer cell line assays were performed to evaluate uptake of 3H- or 14C-labeled L-leucine and other essential amino acids. Both L-leucine and 5- [18F]fluoroleucine were tested for uptake and accumulation over time, and for uptake via LAT1. Biodistribution studies were performed to estimate radiation dosimetry for human studies. Small animal PET / CT studies of a breast cancer were performed to evaluate in vivo 5-[18F]fluoroleucine tumor uptake. Breast cancer cell lines showed increasing high net accumulation of L-[14C]leucine. Both L-leucine and 5-[18F]fluoroleucine showed increasing uptake over time in in vitro tumor cell assays, and uptake was also shown to occur via LAT1. The biodistribution study of 5-[18F]fluoroleucine showed rapid renal excretion, no significant in vivo metabolism, and acceptable dosimetry for use in humans. In vivo small animal PET / CT imaging of a breast cancer xenograft showed uptake of 5- [18F]fluoroleucine in the tumor, which progressively increased over time. 5-[18F]fluoroleucine is a leucine analog which may be useful in identifying tumors with high or upregulated expression of amino acid transporters, providing additional information that may not be provided by FDG PET. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Construction of non-viral vector (mPEG5k-PCL1.2k)1.4-g-PEI10k and its gene delivery efficacy in vitro

OpenAIRE

Wei HUANG; Ming LV; Zhong-gao GAO; Ming-ji JIN; Fei-fei YANG; Yu-li WANG

2011-01-01

Objective To construct(mPEG5k-PCL1.2k)1.4-g-PEI10k,a copolymer designed as delivery vector for non-viral gene therapy,and explore its cytotoxicity and efficacy in delivery of plasmid DNA(pDNA).Methods The copolymer,mPEG5k-PCL1.2k-OH,was prepared by ring-opening polymerization and then followed by a conversion of hydroxyl terminal(-OH) into N-hydroxysuccinimide(NHS) to prepare mPEG5k-PCL1.2k-NHS.One of the branches,PEI10k,was then reacted with mPEG5k-PCL1.2k-NHS to synthesize a ternary copolym...

Biodistribution and radiation dosimetry of the 18 kDa translocator protein (TSPO) radioligand [{sup 18}F]FEDAA1106: a human whole-body PET study

Energy Technology Data Exchange (ETDEWEB)

Takano, Akihiro; Gulyas, Balazs; Varrone, Andrea; Karlsson, Per; Sjoholm, Nils; Halldin, Christer [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm (Sweden); Larsson, Stig; Jonsson, Cathrine; Odh, Richard [Karolinska Institutet, Department of Nuclear Medicine, Stockholm (Sweden); Sparks, Richard [CDE Dosimetry Services, Inc., Knoxville, TN (United States); Tawil, Nabil Al [Karolinska University Hospital, Karolinska Trial Alliance, Stockholm (Sweden); Hoffmann, Anja; Zimmermann, Torsten; Thiele, Andrea [Bayer Schering Pharma AG, Berlin (Germany)

2011-11-15

[{sup 18}F]FEDAA1106 is a recently developed positron emission tomography (PET) radioligand for in vivo quantification of the 18 kDa translocator protein [TSPO or, as earlier called, the peripheral benzodiazepine receptor (PBR)]. TSPO imaging is expected to be useful for the clinical evaluation of neuroinflammatory diseases. The aim of this study was to provide dosimetry estimates for [{sup 18}F]FEDAA1106 based on human whole-body PET measurements. PET scans were performed for a total of 6.6 h after the injection of 183.8 {+-} 9.1 MBq of [{sup 18}F]FEDAA1106 in six healthy subjects. Regions of interest were drawn on coronal images. Estimates of the absorbed doses of radiation were calculated using the OLINDA software. Peak uptake was largest in lungs, followed by liver, small intestine, kidney, spleen and other organs. Peak values of the percent injected dose (%ID) at a time after radioligand injection were calculated for the lungs (27.1%ID at 0.2 h), liver (21.1%ID at 0.6 h), small intestine (10.4%ID at 6.3 h), kidney (4.9%ID at 1.8 h) and spleen (4.6%ID at 0.6 h). The largest absorbed dose was found in the spleen (0.12 mSv/MBq), followed by kidneys (0.094 mSv/MBq). The calculated mean effective dose was 0.036 mSv/MBq. Based on the distribution and dose estimates, the estimated radiation burden of [{sup 18}F]FEDAA1106 is moderately higher than that of [{sup 18}F]fluorodeoxyglucose (FDG). In clinical studies, the administered activity of this radioligand ought to be adjusted in line with regional regulations. This result would be helpful for further clinical TSPO imaging studies. (orig.)

Diagnostic and prognostic value of 18F-FDG PET/CT in recurrent germinal tumor carcinoma

Energy Technology Data Exchange (ETDEWEB)

Alongi, Pierpaolo [IRCSS San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); San Raffaele G. Giglio Institute, Department of Radiological Sciences, Nuclear Medicine Unit, Cefalu (Italy); Evangelista, Laura [Veneto Institute of Oncology IOV - IRCCS, Nuclear Medicine and Molecular Imaging Unit, Padua (Italy); Caobelli, Federico [Basel University Hospital, Department of Nuclear Medicine, Basel (Switzerland); Spallino, Marianna [University of Milano-Bicocca, Milan (Italy); Gianolli, Luigi; Picchio, Maria [IRCSS San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); Midiri, Massimo [San Raffaele G. Giglio Institute, Department of Radiological Sciences, Nuclear Medicine Unit, Cefalu (Italy); University of Palermo, Department of Radiology, DIBIMED, Palermo (Italy)

2018-01-15

38%, respectively; p = 0.02). An unremarkable scan was associated also with a longer OS (98% after 2 years and 95% after 5 years, p = 0.02). At univariate Cox regression analysis, a pathological {sup 18}F-FDG PET/CT scan was associated with an increased risk of disease progression (HR = 24.3, CI 95% 14.1-40.6; p = 0.03) and lower OS (HR = 17.3 CI 95% 4,9-77; p < 0.001). Its prognostic value was confirmed also if tested against advanced disease at diagnosis and rising Human Chorionic Gonadotropin Beta (HCGB) or Alpha-Fetoprotein (AFP) (HR = 7.3 for STAGE III-PET+, p = 0.03; HR = 14.3 elevated HCGB-PET+, p = 0.02; HR 10.7 elevated AFP-PET+, p = 0.01) At multivariate analysis, only a pathological {sup 18}F-FDG PET/CT scan and advanced disease in terms of TNM staging were predictors of disease progression and OS. {sup 18}F-FDG PET/CT showed incremental value over other variables both in predicting PFS (chi-square from 24 to 40, p < 0.001) and OS (chi-square from 32 to 38, p = 0.003). {sup 18}F-FDG PET/CT has a very good diagnostic performance in patients with suspected recurrent GCT and has an important prognostic value in assessing the rate of PFS and OS. Furthermore, {sup 18}F-FDG PET/CT impacted the therapeutic regimen in 23% of patients, thus providing a significant impact in the restaging process. (orig.)

Diagnostic and prognostic value of 18F-FDG PET/CT in recurrent germinal tumor carcinoma.

Science.gov (United States)

Alongi, Pierpaolo; Evangelista, Laura; Caobelli, Federico; Spallino, Marianna; Gianolli, Luigi; Midiri, Massimo; Picchio, Maria

2018-01-01

longer OS (98% after 2 years and 95% after 5 years, p = 0.02). At univariate Cox regression analysis, a pathological 18 F-FDG PET/CT scan was associated with an increased risk of disease progression (HR = 24.3, CI 95% 14.1-40.6; p = 0.03) and lower OS (HR = 17.3 CI 95% 4,9-77; p < 0.001). Its prognostic value was confirmed also if tested against advanced disease at diagnosis and rising Human Chorionic Gonadotropin Beta (HCGB) or Alpha-Fetoprotein (AFP) (HR = 7.3 for STAGE III-PET+, p = 0.03; HR = 14.3 elevated HCGB-PET+, p = 0.02; HR 10.7 elevated AFP-PET+, p = 0.01) At multivariate analysis, only a pathological 18 F-FDG PET/CT scan and advanced disease in terms of TNM staging were predictors of disease progression and OS. 18 F-FDG PET/CT showed incremental value over other variables both in predicting PFS (chi-square from 24 to 40, p < 0.001) and OS (chi-square from 32 to 38, p = 0.003). 18 F-FDG PET/CT has a very good diagnostic performance in patients with suspected recurrent GCT and has an important prognostic value in assessing the rate of PFS and OS. Furthermore, 18 F-FDG PET/CT impacted the therapeutic regimen in 23% of patients, thus providing a significant impact in the restaging process.

Diagnostic and prognostic value of 18F-FDG PET/CT in recurrent germinal tumor carcinoma

International Nuclear Information System (INIS)

Alongi, Pierpaolo; Evangelista, Laura; Caobelli, Federico; Spallino, Marianna; Gianolli, Luigi; Picchio, Maria; Midiri, Massimo

2018-01-01

unremarkable scan was associated also with a longer OS (98% after 2 years and 95% after 5 years, p = 0.02). At univariate Cox regression analysis, a pathological 18 F-FDG PET/CT scan was associated with an increased risk of disease progression (HR = 24.3, CI 95% 14.1-40.6; p = 0.03) and lower OS (HR = 17.3 CI 95% 4,9-77; p < 0.001). Its prognostic value was confirmed also if tested against advanced disease at diagnosis and rising Human Chorionic Gonadotropin Beta (HCGB) or Alpha-Fetoprotein (AFP) (HR = 7.3 for STAGE III-PET+, p = 0.03; HR = 14.3 elevated HCGB-PET+, p = 0.02; HR 10.7 elevated AFP-PET+, p = 0.01) At multivariate analysis, only a pathological 18 F-FDG PET/CT scan and advanced disease in terms of TNM staging were predictors of disease progression and OS. 18 F-FDG PET/CT showed incremental value over other variables both in predicting PFS (chi-square from 24 to 40, p < 0.001) and OS (chi-square from 32 to 38, p = 0.003). 18 F-FDG PET/CT has a very good diagnostic performance in patients with suspected recurrent GCT and has an important prognostic value in assessing the rate of PFS and OS. Furthermore, 18 F-FDG PET/CT impacted the therapeutic regimen in 23% of patients, thus providing a significant impact in the restaging process. (orig.)

One-Step 18F-Labeling of Estradiol Derivative for PET Imaging of Breast Cancer

Directory of Open Access Journals (Sweden)

Hongbo Huang

2018-01-01

Full Text Available Positron emission tomography (PET imaging is a useful method to evaluate in situ estrogen receptor (ER status for the early diagnosis of breast cancer and optimization of the appropriate treatment strategy. The 18F-labeled estradiol derivative has been successfully used to clinically assess the ER level of breast cancer. In order to simplify the radiosynthesis process, one-step 18F-19F isotope exchange reaction was employed for the 18F-fluorination of the tracer of [18F]AmBF3-TEG-ES. The radiotracer was obtained with the radiochemical yield (RCY of ~61% and the radiochemical purity (RCP of >98% within 40 min. Cell uptake and blocking assays indicated that the tracer could selectively accumulate in the ER-positive human breast cancer cell lines MCF-7 and T47D. In vivo PET imaging on the MCF-7 tumor-bearing mice showed relatively high tumor uptake (1.4~2.3 %D/g and tumor/muscle uptake ratio (4~6. These results indicated that the tracer is a promising PET imaging agent for ER-positive breast cancers.

[18F]FDG is not transported by P-glycoprotein and breast cancer resistance protein at the rodent blood–brain barrier

International Nuclear Information System (INIS)

Wanek, Thomas; Traxl, Alexander; Bankstahl, Jens P.; Bankstahl, Marion; Sauberer, Michael; Langer, Oliver; Kuntner, Claudia

2015-01-01

Introduction: Transport of 2-[ 18 F]fluoro-2-deoxy-D-glucose ([ 18 F]FDG) by the multidrug efflux transporters P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) at the blood–brain barrier (BBB) may confound the interpretation of [ 18 F]FDG brain PET data. Aim of this study was to assess the influence of ABCB1 and ABCG2 at the BBB on brain distribution of [ 18 F]FDG in vivo by performing [ 18 F]FDG PET scans in wild-type and transporter knockout mice and by evaluating changes in [ 18 F]FDG brain distribution after transporter inhibition. Methods: Dynamic small-animal PET experiments (60 min) were performed with [ 18 F]FDG in groups of wild-type and transporter knockout mice (Abcb1a/b (−/−) , Abcg2 (−/−) and Abcb1a/b (−/−) Abcg2 (−/−) ) and in wild-type rats without and with i.v. pretreatment with the known ABCB1 inhibitor tariquidar (15 mg/kg, given at 2 h before PET). Blood was sampled from animals from the orbital sinus vein at the end of the PET scans and measured in a gamma counter. Brain uptake of [ 18 F]FDG was expressed as the brain-to-blood radioactivity concentration ratio in the last PET time frame (K b,brain ). Results: K b,brain values of [ 18 F]FDG were not significantly different between different mouse types both without and with tariquidar pretreatment. The blood-to-brain transfer rate constant of [ 18 F]FDG was significantly lower in tariquidar-treated as compared with vehicle-treated rats (0.350 ± 0.025 mL/min/g versus 0.416 ± 0.024 mL/min/g, p = 0.026, paired t-test) but K b,brain values were not significantly different between both rat groups. Conclusion: Our results show that [ 18 F]FDG is not transported by Abcb1 at the mouse and rat BBB in vivo. In addition we found no evidence for Abcg2 transport of [ 18 F]FDG at the mouse BBB. Advances in knowledge and implications for patient care: Our findings imply that functional activity of ABCB1 and ABCG2 at the BBB does not need to be taken into account when

Membership, binarity, and rotation of F-G-K stars in the open cluster Blanco 1

Science.gov (United States)

Mermilliod, J.-C.; Platais, I.; James, D. J.; Grenon, M.; Cargile, P. A.

2008-07-01

Context: The nearby open cluster Blanco 1 is of considerable astrophysical interest for formation and evolution studies of open clusters because it is the third highest Galactic latitude cluster known. It has been observed often, but so far no definitive and comprehensive membership determination is readily available. Aims: An observing programme was carried out to study the stellar population of Blanco 1, and especially the membership and binary frequency of the F5-K0 dwarfs. Methods: We obtained radial-velocities with the CORAVEL spectrograph in the field of Blanco 1 for a sample of 148 F-G-K candidate stars in the magnitude range 10 rate reaches 40% (27/68) if one includes the photometric binaries. The cluster mean heliocentric radial velocity is +5.53 ± 0.11 km s-1 based on the most reliable 49 members. The V sin i distribution is similar to that of the Pleiades, confirming the age similarities between the two clusters. Conclusions: This study clearly demonstrates that, in spite of the cluster's high Galactic latitude, three membership criteria - radial velocity, proper motion, and photometry - are necessary for performing a reliable membership selection. Furthermore, even with accurate and extensive data, ambiguous cases still remain. Based on observations collected with the Danish 1.54-m and the Swiss telescopes at the European Southern Observatory, La Silla, Chile, and with the old YALO 1-m telescope at the Cerro Tololo InterAmerican Observatory, Chile. Table [see full textsee full textsee full textsee full textsee full textsee full text] is also available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/485/95

Evaluation of F-18-labeled amino acid derivatives and [18F]FDG as PET probes in a brain tumor-bearing animal model

International Nuclear Information System (INIS)

Wang, H.-E.; Wu, S.-Y.; Chang, C.-W.; Liu, R.-S.; Hwang, L.-C.; Lee, T.-W.; Chen, J.-C.; Hwang, J.-J.

2005-01-01

2-Deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) has been extensively used as positron emission tomography (PET) tracer in clinical tumor imaging. This study compared the pharmacokinetics of two 18 F-labeled amino acid derivatives, O-2-[ 18 F]fluoroethyl-L-tyrosine (L-[ 18 F]FET) and 4-borono-2-[ 18 F]fluoro-L-phenylalanine-fructose (L-[ 18 F]FBPA-Fr), to that of [ 18 F]FDG in an animal brain tumor model. Methods: A self-modified automated PET tracer synthesizer was used to produce no-carrier-added (nca) L-[ 18 F]FET. The cellular uptake, biodistribution, autoradiography and microPET imaging of L-[ 18 F]FET, L-[ 18 F]FBPA-Fr and [ 18 F]FDG were performed with F98 glioma cell culture and F98 glioma-bearing Fischer344 rats. Results: The radiochemical purity of L-[ 18 F]FET was >98% and the radiochemical yield was 50% in average of 16 runs. The uptake of L-[ 18 F]FET and L-[ 18 F]FBPA-Fr in the F98 glioma cells increased rapidly for the first 5 min and reached a steady-state level after 10 min of incubation, whereas the cellular uptake of [ 18 F]FDG kept increasing during the study period. The biodistribution of L-[ 18 F]FET, L-[ 18 F]FBPA-Fr and [ 18 F]FDG in the brain tumors was 1.26±0.22, 0.86±0.08 and 2.77±0.44 %ID/g at 60 min postinjection, respectively, while the tumor-to-normal brain ratios of L-[ 18 F]FET (3.15) and L-[ 18 F]FBPA-Fr (3.44) were higher than that of [ 18 F]FDG (1.44). Both microPET images and autoradiograms of L-[ 18 F]FET and L-[ 18 F]FBPA-Fr exhibited remarkable uptake with high contrast in the brain tumor, whereas [ 18 F]FDG showed high uptake in the normal brain and gave blurred brain tumor images. Conclusion: Both L-[ 18 F]FET and L-[ 18 F]FBPA-Fr are superior to [ 18 F]FDG for the brain tumor imaging as shown in this study with microPET

Are percutaneous transgastric biopsies using 14-,16- and 18-G Tru-Cut needles safe? An experimental study in the rabbit

International Nuclear Information System (INIS)

Akan, H.; Incesu, L.; Gunes, M.; Ozen, N.; Gumus, S.

1998-01-01

We evaluated perforation, peritonitis and bleeding after 14-, 16-, 18-G Tru-Cut needles were passed through the stomach in an animal model. Insertions were performed on seven anesthetized rabbits with 18-,16-and 14-G needles simulating the clinical technique. Diluted contrast medium with methylene blue (60mL) was administered through a nasogastric tube after the biopsy. Computed tomography (CT) scanning of the upper abdomen was performed 10 minutes after the insertion for leakage. The abdominal contents were inspected by laparotomy. There was no contrast medium leakage outside the gastrointestinal tract on CT images. Neither methylene blue nor other stomach content leakage was identified by laparotomy, even with manual squeezing. A tiny spot of blood was observed on the serosal surface of the stomach with the 18-G needle passes (five cases), whereas a relatively large haematoma was present with 14-G needle (four cases). Six of the rabbits survived and one died due to an inadvertant aortic injury. The results of the study show that transgastric route with an 1 8-G cutting needle can be used without fear of peritonitis and bleeding. Copyright (1998) Blackwell Science Pty Ltd

Are percutaneous transgastric biopsies using 14-,16- and 18-G Tru-Cut needles safe? An experimental study in the rabbit

Energy Technology Data Exchange (ETDEWEB)

Akan, H.; Incesu, L.; Gunes, M. [Ondokuz Mayis University Medical School, Samsun (Turkey). Department of Radiology; Ozen, N.; Gumus, S. [Ondokuz Mayis University Medical School, Samsun (Turkey). Department of Surgery

1998-05-01

We evaluated perforation, peritonitis and bleeding after 14-, 16-, 18-G Tru-Cut needles were passed through the stomach in an animal model. Insertions were performed on seven anesthetized rabbits with 18-,16-and 14-G needles simulating the clinical technique. Diluted contrast medium with methylene blue (60mL) was administered through a nasogastric tube after the biopsy. Computed tomography (CT) scanning of the upper abdomen was performed 10 minutes after the insertion for leakage. The abdominal contents were inspected by laparotomy. There was no contrast medium leakage outside the gastrointestinal tract on CT images. Neither methylene blue nor other stomach content leakage was identified by laparotomy, even with manual squeezing. A tiny spot of blood was observed on the serosal surface of the stomach with the 18-G needle passes (five cases), whereas a relatively large haematoma was present with 14-G needle (four cases). Six of the rabbits survived and one died due to an inadvertant aortic injury. The results of the study show that transgastric route with an 1 8-G cutting needle can be used without fear of peritonitis and bleeding. Copyright (1998) Blackwell Science Pty Ltd 19 refs., 1 tab., 1 fig.

Heat treatment for improvement in lower temperature mechanical properties of 0.40 pct C-Cr-Mo ultrahigh strength steel

Science.gov (United States)

Tomita, Yoshiyuki; Okabayashi, Kunio

1983-11-01

In the previous paper, it was reported that isothermal heat treatment of a commercial Japanese 0.40 pct C-Ni-Cr-Mo ultrahigh strength steel (AISI 4340 type) at 593 K for a short time followed by water quenching, in which a mixed structure of 25 vol pct lower bainite and 75 vol pct martensite is produced, results in the improvement of low temperature mechanical properties (287 to 123 K). The purpose of this paper is to study whether above new heat treatment will still be effective in commercial practice for improving low temperature mechanical properties of the ultrahigh strength steel when applied to a commercial Japanese 0.40 pct C-Cr-Mo ultrahigh strength steel which is economical because it lacks the expensive nickel component (AISI 4140 type). At and above 203 K this new heat treatment, as compared with the conventional 1133 K direct water quenching treatment, significantly improved the strength, tensile ductility, and notch toughness of the 0.40 pct C-Cr-Mo ultrahigh strength steel. At and above 203 K the new heat treatment also produced superior fracture ductility and notch toughness results at similar strength levels as compared to those obtained by using γ α' repetitive heat treatment for the same steel. However, the new heat treatment remarkably decreased fracture ductility and notch toughness of the 0.40 pct C-Cr-Mo ultrahigh strength steel below 203 K, and thus no significant improvement in the mechanical properties was noticeable as compared with the properties produced by the conventional 1133 K direct water quenching treatment and the γ α' repetitive heat treatment. This contrasts with the fact that the new heat treatment, as compared with the conventional 1133 K direct water quenching treatment and the γ α' repetitive heat treatment, dramatically improved the notch toughness of the 0.40 pct C-Ni-Cr-Mo ultrahigh strength steel, providing a better combination of strength and ductility throughout the 287 to 123 K temperature range. The difference

Positron emission tomography imaging of cardiomyocyte apoptosis with a novel molecule probe [18F]FP-DPAZn2

Science.gov (United States)

Sun, Ting; Tang, Ganghua; Tian, Hua; Hu, Kongzhen; Yao, Shaobo; Su, Yifan; Wang, Changqian

2015-01-01

Cardiomyocyte apoptosis plays a causal role in the development and progression of heart failure. Currently, there is no effective imaging agent that can be used to detect cardiomyocyte apoptosis in vivo. To target phosphatidylserine (PS) on the surface of the dying cell, we synthesized a novel 18F-labeled Zn2+-dipicolylamine (DPA) analog, [18F]FP-DPAZn2, and evaluated it for noninvasive imaging of cardiomyocyte apoptosis. In vitro, the fluorescence imaging of dansyl-DPAZn2 was suitable for detecting cardiomyocyte apoptosis, which was confirmed by confocal immunofluorescence imaging, terminal dUTP nick-end labeling (TUNEL) assay, and western blot assay. The in vivo biodistribution showed that the uptake ratios of [18F]FP-DPAZn2 in the heart were 4.41±0.29% ID/g at 5 min, 2.40 ± 0.43% ID/g at 30 min, 1.63 ± 0.26% ID/g at 60 min, and 1.43% ± 0.07 ID/g at 120 min post-injection. In vivo, the [18F]FP-DPAZn2 PET images showed more cardiac accumulation of radioactivity 60 min post-injection in acute myocardial infarction (AMI) rats than in normal rats, which was consistent with the findings of a histological analysis of the rat cardiac tissues in vitro. [18F]FP-DPAZn2 PET imaging has the capability for myocardial apoptosis detection, but the method will require improved myocardial uptake for the noninvasive evaluation of cardiomyocyte apoptosis in clinical settings. PMID:26416423

Tritium in [18O]water containing [18F]fluoride for [18F]FDG synthesis

International Nuclear Information System (INIS)

Ito, Shigeki; Saze, Takuya; Sakane, Hitoshi; Ito, Satoshi; Ito, Shinichi; Nishizawa, Kunihide

2004-01-01

The presence of tritium in enriched [ 18 O]water irradiated with 9.6 MeV protons used to produce [ 18 F]fluoride by the 18 O(p, n) 18 F reaction was inferred from the cross sections and threshold energies of the 18 O(p, t) 16 O reaction, and the existence of tritium was confirmed experimentally. Tritium was also detected in both [ 18 O]water recovered for recycling and waste acetonitrile solutions. The purified [ 18 F]FDG was not contaminated with 3 H. The amount of 3 H discharged into the air was far less than the International Basic Safety Standard Level

WE-H-207A-05: Spatial Co-Localization of F-18 NaF Vs. F-18 FDG Defined Disease Volumes

Energy Technology Data Exchange (ETDEWEB)

Ferjancic, P; Harmon, S; Jeraj, R [University of Wisconsin, Madison, WI (United States); Chen, S [1st Hospital of China Medical University, Shenyang, Liaoning (China); Simoncic, U [Jozef Stefan Institute, Ljubljana (Slovenia)

2016-06-15

Purpose: Both [F-18]NaF and [F-18]FDG show promise for quantitative PET/CT assessment in metastatic prostate cancer to bone. Broad agreement between the tracers has been shown but voxel-wise correspondence has not been explored in depth. This study evaluates the spatial co-localization of [F-18]NaF PET and [F-18]FDG PET in bone lesions. Methods: Seventy-three lesion contours were identified in six patients receiving dynamic NaF PET/CT and FDG PET/CT scans two hours apart using identical fields-of-view. Tracer uptake (SUV) reflecting 60 minutes post-injection was modeled from kinetic parameters. Lesions were segmented by a physician separately on NaF PET and FDG PET. PET images were rigidly aligned using skeletal references on CT images. Lesion size, degree of overlap, voxel-wise tracer uptake values (SUV), and CT density distributions were compared using Dice coefficient, Positive Predictive Value (PPV), and Spearman rank correlation tests. Results: Across all patients, 42 lesions were identified on NaF PET (median 1.4 cm{sup 3}, range <1–204 cm{sup 3}) compared to 31 using FDG PET (median 1.8 cm{sup 3}, range <1–244 cm{sup 3}). Spatial cooccurrence was found in 25 lesion pairs. Lesions on NaF PET had PPV of 0.91 and on FDG a PPV of 0.65. Overall, NaF-defined lesions were 47% (±24%) larger by volume with moderate overlap to FDG, resulting in mean Dice coefficient of 34% (±22%). In areas of overlap, voxel-wise correlation of NaF and FDG SUV was moderate (ρ=0.56). Expanding to regions of non-spatial overlap, voxels contained in FDG-only contours were almost exclusively low HU (median 118), compared to dense regions of NaF-only voxels (median 250). In sclerotic sub-volumes (HU > 300) NaF-defined contours encompassed 83% of total FDG volume. Conclusion: Moderate voxel-wise correlation of FDG and NaF PET/CT uptake was observed. Spatial discrepancies in FDG and NaF PET/CT imaging of boney metastases could be influenced by poor sensitivity of FDG PET/CT in

Stress corrosion (Astm G30-90 standard) in 08x18H10T stainless steel of nuclear fuel storage pool in WWER reactors

International Nuclear Information System (INIS)

Herrera, V.; Zamora R, L.

1997-01-01

At the water storage of the irradiated nuclear fuel has been an important factor in its management. The actual pools have its walls covered with inoxidable steel and heat exchangers to dissipate the residual heat from fuel. It is essential to control the water purity to eliminate those conditions which aid to the corrosion process in fuel and at related components. The steel used in this research was obtained from an austenitic inoxidizable steel standardized with titanium 08x18H10T (Type 321) similar to one of the two steel coatings used to cover walls and the pools floor. the test consisted in the specimen deformation through an U ply according to the Astm G30-90 standard. The exposition of the deformed specimen it was realized in simulated conditions to the chemical regime used in pools. (Author)

Structural transformations in austenitic stainless steel induced by deuterium implantation: irradiation at 100 K.

Science.gov (United States)

Morozov, Oleksandr; Zhurba, Volodymyr; Neklyudov, Ivan; Mats, Oleksandr; Rud, Aleksandr; Chernyak, Nikolay; Progolaieva, Viktoria

2015-01-01

Deuterium thermal desorption spectra were investigated on the samples of austenitic stainless steel 18Cr10NiTi preimplanted at 100 K with deuterium ions in the dose range from 3 × 10(15) to 5 × 10(18) D/cm(2). The kinetics of structural transformation development in the implantation steel layer was traced from deuterium thermodesorption spectra as a function of implanted deuterium concentration. At saturation of austenitic stainless steel 18Cr10NiTi with deuterium by means of ion implantation, structural-phase changes take place, depending on the dose of implanted deuterium. The maximum attainable concentration of deuterium in steel is C = 1 (at.D/at.met. = 1/1). The increase in the implanted dose of deuterium is accompanied by the increase in the retained deuterium content, and as soon as the deuterium concentration attains C ≈ 0.5 the process of shear martensitic structural transformation in steel takes place. It includes the formation of bands, body-centered cubic (bcc) crystal structure, and the ferromagnetic phase. Upon reaching the deuterium concentration C > 0.5, the presence of these molecules causes shear martensitic structural transformations in the steel, which include the formation of characteristic bands, bcc crystal structure, and the ferromagnetic phase. At C ≥ 0.5, two hydride phases are formed in the steel, the decay temperatures of which are 240 and 275 K. The hydride phases are formed in the bcc structure resulting from the martensitic structural transformation in steel.

Formed electroslag welded joint from austenitic steel 18/10 CrNi

International Nuclear Information System (INIS)

Jilek, L.; Kusak, L.; Martinak, A.

1987-01-01

The electroslag welded joint from titanium stabilized steel 18/10 CrNi of 150 mm in thickness showed positive results for both nondestructive and destructive testing. Czechoslovak flux VUZ-4F and the optimized welding mode were completely proven. The weldment was subject to deformation by forging with a removal of 20 to 50% and to bending deformation. A 40% to 50% deformation was necessary for breaking the coarse-grain casting structure. The bending deformation resulted in breaking the coarse-grain casting structure in the entire cross-section, it was, however, only acting in a narrow band corresponding to the largest curvature. At the same time, the heat affected zone decayed. Following heat treatment, especially forming, the delta ferrite content in the weld metal decreased, the mechanical properties of the weld metal and the welded joint following welding and heat treatment showed a relatively large scatter. Forming reduced the scatter and improved plastic properties. Machining within 40 and 50% resulted in good echogenicity of the welded joint in ultrasound testing. The welded joint showed equal properties as the base material of the weldment. (author). 15 figs., 2 tabs., 16 refs

Evaluation of 18F-FDG and 18F-FLT for monitoring therapeutic responses of colorectal cancer cells to radiotherapy

International Nuclear Information System (INIS)

Wang, Hui; Liu, Bo; Tian, Jiahe; Xu, Baixuan; Zhang, Jinming; Qu, Baolin; Chen, Yingmao

2013-01-01

In order to compare the efficacy of 18 F-fluorothymidine (FLT) and 18 F-fluorodeoxyglucose (FDG) for monitoring early responses to irradiation, two human colorectal cancer (CRC) cell lines SW480 and SW620, which were derived from the primary lesions and the metastatic lymph node, underwent X-ray irradiation of 0, 10, or 20 Gy and were examined at 0, 24 and 72 h After irradiation, reduced proliferation of both SW480 and SW620 cells was observed in a dose-dependent manner (P < 0.001), G0-G1 arrest was also noted in both cell types after 72 h in the 20 Gy group (P < 0.001). Although increased apoptosis was observed in both cell lines after irradiation (P < 0.001), a greater percentage of SW480 cells underwent apoptosis in response to irradiation than SW620 cells. Increased Hsp27 and decreased integrin β 3 , Ki67 and VEGFR2 expression was observed over time via immunocytochemistry and Western blot analysis (P < 0.001), however, no significant changes were noted in response to irradiation. Finally, reduced uptake of 18 F-FLT by SW480 or SW620 cells was observed at 24-h post-irradiation, however, reduced 18 F-FDG uptake was only observed after 72 h. Therefore, we conclude that 18 F-FLT is a more suitable positron emission tomography (PET) tracer for monitoring early responses to irradiation in primary and metastatic lymph node CRC cells

A Study on the Fatigue-Fractured Surface of Normalized SS41 Steel and M.E.F. Dual Phase Steel by an X-ray Diffraction Technique

International Nuclear Information System (INIS)

Oh, Sae Wook; Park, Young Chul; Park, Soo Young; Kim, Deug Jin; Hue, Sun Chul

1996-01-01

This study verified the relationship between fracture mechanics parameters and X-ray parameters for normalized SS41 steel with homogeneous crystal structure and M.E.F. dual phase steel(martensite encapsulated islands of ferrite). The fatigue crack propagation test were carried out and X-ray diffraction technique was applied to fatigue fractured surface. The change in X-ray parameters(residual stress, half-value breadth) according to the depth of fatigue fractured surface were investigated. The depth of maximum plastic zone, W y , were determined on the basis of the distribution of the half-value breadth for normalized SS41 steel and that of the residual stress for M.E.F. dual phase steel. K max could be estimated by the measurement of W y

A “dose on demand” Biomarker Generator for automated production of [18F]F− and [18F]FDG

International Nuclear Information System (INIS)

Awasthi, V.; Watson, J.; Gali, H.; Matlock, G.; McFarland, A.; Bailey, J.; Anzellotti, A.

2014-01-01

The University of Oklahoma—College of Pharmacy has installed the first Biomarker Generator (BG75) comprising a self-shielded 7.5-MeV proton beam positive ion cyclotron and an aseptic automated chemistry production and quality control module for production of [ 18 F]F − and clinical [ 18 F]FDG. Performance, reliability, and safety of the system for the production of “dose on demand” were tested over several months. No-carrier-added [ 18 F]F − was obtained through the 18 O(p,n) 18 F nuclear reaction by irradiation (20–40 min) of a >95% enriched [ 18 O]H 2 O target (280 μl) with a 7.5-MeV proton beam (3.5–5.0 μA). Automated quality control tests were performed on each dose. The HPLC-based analytical methods were validated against USP methods of quality control. [ 18 F]FDG produced by BG75 was tested in a mouse tumor model implanted with H441 human lung adenocarcinoma cells. After initial installment and optimization, the [ 18 F]F − production has been consistent since March 2011 with a maximum production of 400 to 450 mCi in a day. The average yield is 0.61 mCi/min and 0.92 mCi/min at 3.8 µA and 5 µA, respectively. The current target window has held up for over 25 weeks against >400 bombardment cycles. [ 18 F]FDG production has been consistent since June 2012 with an average of six doses/day in an automated synthesis mode (RCY≈50%). The release criteria included USP-specified limits for pH, residual solvents (acetonitrile/ethanol), kryptofix, radiochemical purity/identity, and filter integrity test. The entire automated operation generated minimal radiation exposure hazard to the operator and environment. As expected, [ 18 F]FDG produced by BG75 was found to delineate tumor volume in a mouse model of xenograft tumor. In summary, production and quality control of “[ 18 F]FDG dose on demand” have been accomplished in an automated and safe manner by the first Biomarker Generator. The implementation of a cGMP quality system is under way towards

The K2 Ecliptic Plane Input Catalog (EPIC) and Stellar Classifications of 138,600 Targets in Campaigns 1-8

Science.gov (United States)

Huber, Daniel; Bryson, Stephen T.; Haas, Michael R.; Barclay, Thomas; Barentsen, Geert; Howell, Steve B.; Sharma, Sanjib; Stello, Dennis; Thompson, Susan E.

2016-05-01

The K2 Mission uses the Kepler spacecraft to obtain high-precision photometry over ≈80 day campaigns in the ecliptic plane. The Ecliptic Plane Input Catalog (EPIC) provides coordinates, photometry, and kinematics based on a federation of all-sky catalogs to support target selection and target management for the K2 mission. We describe the construction of the EPIC, as well as modifications and shortcomings of the catalog. Kepler magnitudes (Kp) are shown to be accurate to ≈0.1 mag for the Kepler field, and the EPIC is typically complete to Kp ≈ 17 (Kp ≈ 19 for campaigns covered by Sloan Digital Sky Survey). We furthermore classify 138,600 targets in Campaigns 1-8 (≈88% of the full target sample) using colors, proper motions, spectroscopy, parallaxes, and galactic population synthesis models, with typical uncertainties for G-type stars of ≈3% in {T}{{eff}}, ≈0.3 dex in {log} g, ≈40% in radius, ≈10% in mass, and ≈40% in distance. Our results show that stars targeted by K2 are dominated by K-M dwarfs (≈41% of all selected targets), F-G dwarfs (≈36%), and K giants (≈21%), consistent with key K2 science programs to search for transiting exoplanets and galactic archeology studies using oscillating red giants. However, we find significant variation of the fraction of cool dwarfs with galactic latitude, indicating a target selection bias due to interstellar reddening and increased contamination by giant stars near the galactic plane. We discuss possible systematic errors in the derived stellar properties, and differences with published classifications for K2 exoplanet host stars. The EPIC is hosted at the Mikulski Archive for Space Telescopes (MAST): http://archive.stsci.edu/k2/epic/search.php.

Prediction of fracture toughness K/sub Ic/ of steel from Charpy impact test results

Energy Technology Data Exchange (ETDEWEB)

Iwadate, Tadao; Tanaka, Yasuhiko; Takemata, Hiroyuki; Terashima, Shuhei

1986-08-01

This paper presents a method to predict the fracture toughness K/sub Ic/ and/or K/sub Id/ of steels using their Charpy impact test results and tensile properties. The fracture toughness, Charpy impact and tensile properties of 2 1/4 Cr-1Mo, ASTM A508 Cl.1, A508 Cl.2 A508 Cl.3 and A533 Gr.B Cl.1 steels were measured and analysed on the basis of the excess temperature (test temperature minus FATT) and Rolfe-Novak correlation. The relationship between K/sub Ic//K/sub Ic-us/ and the excess temperature, where K/sub Ic-us/ is the upper-shelf fracture toughness K/sub Ic/ predicted by Rolfe-Novak correlation, discloses that the K/sub Ic/ transition curves of several steels are representable by only one trend curve of K/sub Ic//K/sub Ic-us/ or K/sub Id//K/sub Id-us/ versus excess temperature relation. This curve is denoted as a ''master curve''. By using this curve, the fracture toughness of steel can be predicted using Charpy impact and tensile test results. By taking account of the scattering of both the fracture toughness and Charpy impact test results, the confidence limits of the master curve were also determined. Another approach to develop more general procedure of predicting the fracture toughness K/sub Ic/ is also discussed.

Clinically relevant strategies for lowering cardiomyocyte glucose uptake for 18F-FDG imaging of myocardial inflammation in mice

International Nuclear Information System (INIS)

Thackeray, James T.; Bankstahl, Jens P.; Bengel, Frank M.; Wang, Yong; Wollert, Kai C.

2015-01-01

Myocardial inflammation is an emerging target for novel therapies and thus for molecular imaging. Positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) has been employed, but requires an approach for suppression of cardiomyocyte uptake. We tested clinically viable strategies for their suitability in mouse models in order to optimize preclinical imaging protocols. C57BL/6 mice (n = 56) underwent FDG PET under various conditions. In healthy animals, the effect of low-dose (5 units/kg) or high-dose (500 units/kg, 15 min prior) intravenous heparin, extended fasting (18 h) and the impact of conscious injection with limited, late application of isoflurane anaesthesia after 40 min of conscious uptake were examined in comparison to ketamine/xylazine anaesthesia. Conscious injection/uptake strategies were further evaluated at 3 days after permanent coronary artery occlusion. Under continuous isoflurane anaesthesia, neither heparin administration nor extended fasting significantly impacted myocardial 18 F-FDG accumulation. Injection with 40 min uptake in awake mice resulted in a marked reduction of global myocardial 18 F-FDG uptake compared to standard isoflurane anaesthesia (5.7 ± 1.1 %ID/g vs 30.2 ± 7.9 %ID/g, p < 0.01). Addition of heparin and fasting further reduced uptake compared to conscious injection alone (3.8 ± 1.5 %ID/g, p < 0.01) similar to ketamine/xylazine (2.4 ± 2.2 %ID/g, p < 0.001). In the inflammatory phase, 3 days after myocardial infarction, conscious injection/uptake with and without heparin/fasting identified a marked increase in myocardial 18 F-FDG accumulation that was similar to that observed under ketamine/xylazine. Continuous isoflurane anaesthesia obscures any suppressive effect of heparin or fasting on cardiomyocyte glucose utilization. Conscious injection of FDG in rodents significantly reduces cardiomyocyte uptake and enables further suppression by heparin and fasting, similar to clinical observations. In contrast to

[{sup 18}F]FDG PET/CT outperforms [{sup 18}F]FDG PET/MRI in differentiated thyroid cancer

Energy Technology Data Exchange (ETDEWEB)

Vrachimis, Alexis; Wenning, Christian; Weckesser, Matthias; Stegger, Lars [University Hospital Muenster, Department of Nuclear Medicine, Muenster (Germany); Burg, Matthias Christian; Allkemper, Thomas [University Hospital Muenster, Department of Clinical Radiology, Muenster (Germany); Schaefers, Michael [University Hospital Muenster, Department of Nuclear Medicine, Muenster (Germany); Westfaelische Wilhelms University Muenster, European Institute for Molecular Imaging, Muenster (Germany)

2016-02-15

To evaluate the diagnostic potential of PET/MRI with [{sup 18}F]FDG in comparison to PET/CT in patients with differentiated thyroid cancer suspected or known to have dedifferentiated. The study included 31 thyroidectomized and remnant-ablated patients who underwent a scheduled [{sup 18}F]FDG PET/CT scan and were then enrolled for a PET/MRI scan of the neck and thorax. The datasets (PET/CT, PET/MRI) were rated regarding lesion count, conspicuity, diameter and characterization. Standardized uptake values were determined for all [{sup 18}F]FDG-positive lesions. Histology, cytology, and examinations before and after treatment served as the standards of reference. Of 26 patients with a dedifferentiated tumour burden, 25 were correctly identified by both [{sup 18}F]FDG PET/CT and PET/MRI. Detection rates by PET/CT and PET/MRI were 97 % (113 of 116 lesions) and 85 % (99 of 113 lesions) for malignant lesions, and 100 % (48 of 48 lesions) and 77 % (37 of 48 lesions) for benign lesions, respectively. Lesion conspicuity was higher on PET/CT for both malignant and benign pulmonary lesions and in the overall rating for malignant lesions (p < 0.001). There was a difference between PET/CT and PET/MRI in overall evaluation of malignant lesions (p < 0.01) and detection of pulmonary metastases (p < 0.001). Surgical evaluation revealed three malignant lesions missed by both modalities. PET/MRI additionally failed to detect 14 pulmonary metastases and 11 benign lesions. In patients with thyroid cancer and suspected or known dedifferentiation, [{sup 18}F]FDG PET/MRI was inferior to low-dose [{sup 18}F]FDG PET/CT for the assessment of pulmonary status. However, for the assessment of cervical status, [{sup 18}F]FDG PET/MRI was equal to contrast-enhanced neck [{sup 18}F]FDG PET/CT. Therefore, [{sup 18}F]FDG PET/MRI combined with a low-dose CT scan of the thorax may provide an imaging solution when high-quality imaging is needed and high-energy CT is undesirable or the use of a contrast

Full Automatic synthesis of [18F]FMISO

International Nuclear Information System (INIS)

Seung Jun Oh; Se Hun Kang; Jin-Sook Ryu; Dae Hyuk Moon

2004-01-01

[ 18 F]FMISO is a radiopharmaceutical for hypoxia imaging. Although it was developed in 1986, there has been no report about automatic synthesis. In this experiment, we established the full automatic synthesis of [ 18 F]FMISO and evaluate the stability according to ICH guideline. Method: We used GE MicroLab MX for automatic synthesis. Sequence program was modified to control of the module as follows: [ 18 F]Fluoride drying→[ 18 F]fluorination→trapping of reaction mixture on C18 cartridge→purification-elution of reaction mixture→hydrolysis and HPLC purification. We used disposable cassette for each synthesis and discard it after synthesis. To find optimal synthesis condition, we tested 90 120 degree C as reaction temperature, 5 15 mg of 1-(2-nitro-1-imidazolyl) -2-O-tetrahtdropyranyl-3-O-toluenesulfonyl-propanediol as precursor and 5 15 min as [ 18 F]fluorination time. HPLC purification condition was EtOH:H20 = 5:95, 5ml/min with Alltech Econosil column. To check the stability of production, we performed 30 times of run. We checked the radiochemical stability until 6 hours at 25 degree C and 40% humidity condition. We also performed the stability test at 50 70 degree C with 60-80% humidity condition or under UV light for 6 hours after synthesis for acceleration test, Results: The optimal [ 18 F] fluorination condition was 10mg of precursor and 15 min incubation at 110 degree C. Hydrolysis was performed at 105 degree C for 5 min. After HPLC purification, radiochemical yields and purity were 45±2.8 and 98±1.2%, respectively. Total synthesis time was 60±5.2 min. [ 18 F]FMISO was stable until 6 hours after production with 97±2.4% of radiochemical purity. [ 18 F]FMISO was also stable in acceleration test and photochemical test with 97±2.4 and 97±2.8% of radiochemical purity, respectively. Conclusion: We established the full automatic synthesis method of [ 18 F]FMISO with reproducible high production yield. [18F]FMISO synthesized by this method was stable

Microstructure in HIP-bonded F82H steel and its mechanical properties after irradiation

International Nuclear Information System (INIS)

Furuya, K.; Wakai, E.

2006-01-01

A first primary blanket structure is composed of the low-activation steel, e.g. F82H, and is fabricated by using a solid hot isostatic pressing (HIP) bonding method. A partial mock-up of such a blanket structure was successfully fabricated. The tensile specimen including HIP-bonded region possessed a sufficient strength and elongation under a non-irradiated condition as reported in our previous studies. In this study, the microstructures of HIP interface before irradiation were observed by a TEM, and the effects of irradiation on mechanical properties of the HIP-bonded region were also examined. TEM observation and elemental analysis of the HIP-bonded region before the irradiation were performed by using a FE-TEM of HF-2000 equipped with EDX spectroscopy. Tensile specimens (type SS-3) were prepared from a HIP-bonded region and a plate region of the mock-up block. Neutron irradiation was performed up to about 1.9 dpa at about 523 K in JMTR. After the irradiation, tensile test was performed at temperatures of 295 and 523 K. After the tensile test, OM observation at the rupture region and SEM observation at the fracture surface were conducted, respectively. TEM observation and analytical results revealed that the HIP interface possessed many precipitates, and enriched peak spectrum of chromium was detected from the precipitates. In addition, aspect of the spectrum was qualitatively equivalent to that of M23C6 in grain boundaries of F82H steel. In result, the HIP boundary has many M23C6 which were generally seen in grain boundaries of F82H steel, and it can be mentioned that the HIP interface is, in this sense, a new grain boundary. Obvious HIP boundary was seen at rupture region of tensile specimens sampled from the HIP-bonded region, by the macroscopic observation. It means that rupture do not occur in the HIP interface. In result, it can be mentioned that bondability of the HIP interfaces is kept under the irradiation and testing conditions. The strength and

Complementary roles of tumour specific PET tracer {sup 18}F-FAMT to {sup 18}F-FDG PET/CT for the assessment of bone metastasis

Energy Technology Data Exchange (ETDEWEB)

Morita, Motoho [Gunma University Hospital, Department of General Medicine, Maebashi, Gunma (Japan); Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Higuchi, Tetsuya; Tokue, Azusa; Arisaka, Yukiko; Tsushima, Yoshito [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Achmad, Arifudin [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Gadjah Mada University, Department of Radiology, Faculty of Medicine, Yogyakarta (Indonesia)

2013-10-15

The usefulness of {sup 18}F-FDG PET/CT for bone metastasis evaluation has already been established. The amino acid PET tracer [{sup 18}F]-3-fluoro-alpha-methyl tyrosine ({sup 18}F-FAMT) has been reported to be highly specific for malignancy. We evaluated the additional value of {sup 18}F-FAMT PET/CT to complement {sup 18}F-FDG PET/CT in the evaluation of bone metastasis. This retrospective study included 21 patients with bone metastases of various cancers who had undergone both {sup 18}F-FDG and {sup 18}F-FAMT PET/CT within 1 month of each other. {sup 18}F-FDG-avid bone lesions suspicious for malignancy were carefully selected based on the cut-off value for malignancy, and the SUVmax of the {sup 18}F-FAMT in the corresponding lesions were evaluated. A total of 72 {sup 18}F-FDG-positive bone lesions suspected to be metastases in the 21 patients were used as the reference standard. {sup 18}F-FAMT uptake was found in 87.5 % of the lesions. In the lesions of lung cancer origin, the uptake of the two tracers showed a good correlation (40 lesions, r = 0.68, P < 0.01). Bone metastatic lesions of oesophageal cancer showed the highest average of {sup 18}F-FAMT uptake. Bone metastatic lesions of squamous cell carcinoma showed higher {sup 18}F-FAMT uptake than those of adenocarcinoma. No significant difference in {sup 18}F-FAMT uptake was seen between osteoblastic and osteolytic bone metastatic lesions. The usefulness of {sup 18}F-FAMT PET/CT for bone metastasis detection regardless of the lesion phenotype was demonstrated. The fact that {sup 18}F-FAMT uptake was confirmed by {sup 18}F-FDG uptake suggests that {sup 18}F-FAMT PET/CT has the potential to complement {sup 18}F-FDG PET/CT for the detection of bone metastases. (orig.)

18F-FLT Positron Emission Tomography/Computed Tomography Imaging in Pancreatic Cancer: Determination of Tumor Proliferative Activity and Comparison with Glycolytic Activity as Measured by 18F-FDG Positron Emission Tomography/Computed Tomography Imaging

Directory of Open Access Journals (Sweden)

Senait Aknaw Debebe

2016-02-01

Full Text Available Objective: This phase-I imaging study examined the imaging characteristic of 3’-deoxy-3’-(18F-fluorothymidine (18F-FLT positron emission tomography (PET in patients with pancreatic cancer and comparisons were made with (18F-fluorodeoxyglucose (18F-FDG. The ultimate aim was to develop a molecular imaging tool that could better define the biologic characteristics of pancreas cancer, and to identify the patients who could potentially benefit from surgical resection who were deemed inoperable by conventional means of staging. Methods: Six patients with newly diagnosed pancreatic cancer underwent a combined FLT and FDG computed tomography (CT PET/CT imaging protocol. The FLT PET/CT scan was performed within 1 week of FDG PET/CT imaging. Tumor uptake of a tracer was determined and compared using various techniques; statistical thresholding (z score=2.5, and fixed standardized uptake value (SUV thresholds of 1.4 and 2.5, and applying a threshold of 40% of maximum SUV (SUVmax and mean SUV (SUVmean. The correlation of functional tumor volumes (FTV between 18F-FDG and 18F-FLT was assessed using linear regression analysis. Results: It was found that there is a correlation in FTV due to metabolic and proliferation activity when using a threshold of SUV 2.5 for FDG and 1.4 for FLT (r=0.698, p=ns, but a better correlation was obtained when using SUV of 2.5 for both tracers (r=0.698, p=ns. The z score thresholding (z=2.5 method showed lower correlation between the FTVs (r=0.698, p=ns of FDG and FLT PET. Conclusion: Different tumor segmentation techniques yielded varying degrees of correlation in FTV between FLT and FDGPET images. FLT imaging may have a different meaning in determining tumor biology and prognosis.

A comparative investigation of 18F kinetics in receptors: a compartment model analysis

International Nuclear Information System (INIS)

Tiwari, Anjani K.; Swatantra; Kaushik, A.; Mishra, A.K.

2010-01-01

Full text: Some authors reported that 18 F kinetics might be useful for evaluation of neuro receptors. We hypothesized that 18 F kinetics may show some information about neuronal damage, and each rate constant might have statistically significant correlation with WO function. The purpose of this study was to investigate 99m Tc MIBI kinetics through a compartment model analysis. Each rate constant from compartment analysis was compared with WO, T1/2, and (H/M) ratio in early and delayed phase. Different animal model were studied. After an injection the dynamic planar imaging was performed on a dual-headed digital gamma camera system for 30 minutes. An ROI was drawn manually to assess the global kinetics of 18 F. By using the time-activity curve (TAC) of ROI as a response tissue function and the TAC of Aorta as an input function, we analysed 18 F pharmacokinetics through a 2-compartment model. We defined k1 as influx rate constant, k2 as out flux rate constant and k3 as specific uptake rate constant. And we calculated k1/k2 as distribution volume (Vd), k1k3/k2 as specific uptake (SU), and k1k3/(k2+k3) as clearance. For non-competitive affinity studies of PET two modelling parameters distribution volume (DV) and Bmax / Kd are also calculated. Results: Statistically significant correlations were seen between k2 and T1/2 (P 18 F at the injection had relation to the uptake of it at 30 minutes and 2 hours after the injection. Furthermore, some indexes had statistically significant correlation with DV and Bmax. These compartment model approaches may be useful to estimate the other related studies

Chilean experience in production of 18F-FDG from 18F in a reactor

International Nuclear Information System (INIS)

Chandia, M.; Godoy, N.; Errazu, X.; Hernandez; Figols, M.; Firnau, G.; Tronsoco, F.

2000-01-01

18 F-FDG (fluorine-deoxy-D-glucose) is an important and useful radiopharmaceutical for imaging and study of myocardial viability. Usually cyclotron-produced 18 F is used to label 18 F-FDG. The availability of a 5 MW Nuclear Reactor in Chile and the absence of a quality cyclotron to produce 18 F required that we developed a method in order to obtain suitable 18 F to label 18 F-FDG using the facilities we have at the Nuclear Center of La Reina, Chilean Nuclear Energy Commission. The nuclear reactions involved are: 6 Li(n,aα) 3 H and 16 O( 3 H,n) 18 F. Enriched Li 2 CO 3 ( 6 Li = 95 %) was irradiated in a 5 MW swimming pool type nuclear reactor with a neutron flux of 5. 7 x 10 13 n cm -2 s -1 for 4 hours. The irradiated Li 2 CO 3 was dissolved in H 2 SO 4 (1:1) and distilled as trimethylsilyl( 18 F)fluoride ( 18 F-TMS). The labelling of the sugar was carried out using the method described by Hamacker. The 18 F-TMS was trapped in a solution of acetonitrile, water, potassium carbonate, and kriptofix and hydrolysed to form 18 F fluoride. The nucleophilic complex reacts with 1,3,4,6, tetra-O-acetyl- 2-O-trifluoromethanesulfonyl-bβ-D-mannopyranose. The acetylated carbohydrate by acid hydrolysis produces 18 F-FDG. The final product was purified using an ion retarding resin (AG11-A8) and a system two Sep Pak Plus: Alumina and C-18 cartridge and sterilised by Millipore 0.22 μm filter. The 18 F-FDG was obtained in an apyrogenic and sterile solution. The 18 F radionuclide purity was higher than 99.9% and the radiochemical purity ofthe 18 F-FDG obtained was over than 99%. Residual 3 H content was as low as 20 (Bq 3 H/MBq 18 F-FDG.). The yield of the process 18 F-FDG was 13.2 %. (authors)

Diagnosis performance of the positron computed tomography with {sup 18}F-F.D.G. in the Horton disease: meta-analysis; Performances diagnostiques de la tomographie par emission de positons au 18F-FDG dans la maladie de Horton: meta-analyse

Energy Technology Data Exchange (ETDEWEB)

Besson, F.; Costo, S.; Agostini, D. [CHU de Caen, Departement de medecine nucleaire, 14 (France); Dunet, V.; Prior, J. [CHU Vaudois, departement de medecine nucleaire, Lausanne (Switzerland); Hamon, M. [CHU de Caen, Departement de cardiologie, 14 (France); Parienti, J.J. [CHU de Caen, Departement de biostatiques, 14 (France)

2010-07-01

The PET with {sup 18}F-F.D.G. is a sensitive and specific technique to detect Horton disease. It could be used to invalidate the diagnosis among patients suffering of this disease, especially these ones presenting a negative or non contributive temporal artery biopsy or an atypical symptomatology. Furthermore, it should allow to better evaluate the extension of arteritis injuries. (N.C.)

Properties of low-alloy steel with tellurium

International Nuclear Information System (INIS)

Popova, L.V.; Lebedev, D.V.; Litvinenko, D.A.; Nasibov, A.G.

1983-01-01

The results of investigations into 09G2 and 09G2F steels alloyed with tellurium after controlled rolling are presented. 0.002-0.011% tellurium additions did not change strength and plastic properties of the steels after controlled rolling. Tellurium additions results in 40-50% increase of the steel impact strength on samples With circular and sharp cuts in brittle-viscous region. 0.002-0.003% of tellurium is considered to be the optimum content from the view point of increa=. sing steel strength. Increase of impact strength takes place at the expense of growth of both work function of crack formation and work function of crack propagation but in different temperature ranges: at the expense of firstone at 80-40 deg C, at the expense of second one at 20-40 deg C. 0.002-0.011% teilurium additions mainly at the expense of sulphide globularization bring about decrease of anisotropy of steet properties by impact strength reducing anisotropy factor from 2 to 1.5

PET imaging of the brain serotonin transporters (SERT) with N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM) in humans: a preliminary study

International Nuclear Information System (INIS)

Huang, Wen-Sheng; Huang, San-Yuan; Ho, Pei-Shen; Yeh, Chin-Bin; Ma, Kuo-Hsing; Huang, Ya-Yao; Shiue, Chyng-Yann; Liu, Ren-Syuan; Cheng, Cheng-Yi

2013-01-01

The aim of this study was to assess the feasibility of using 4-[ 18 F]-ADAM as a brain SERT imaging agent in humans. Enrolled in the study were 19 healthy Taiwanese subjects (11 men, 8 women; age 33 ± 9 years). The PET data were semiquantitatively analyzed and expressed as specific uptake ratios (SUR) and distribution volume ratios (DVR) using the software package PMOD. The SUR and DVR of 4-[ 18 F]-ADAM in the raphe nucleus (RN), midbrain (MB), thalamus (TH), striatum (STR) and prefrontal cortex (PFC) were determined using the cerebellum (CB) as the reference region. 4-[ 18 F]-ADAM bound to known SERT-rich regions in human brain. The order of the regional brain uptake was MB (RN) > TH > STR > PFC > CB. The DVR (n = 4, t* = 60 min) in the RN, TH, STR and PFC were 3.00 ± 0.50, 2.25 ± 0.45, 2.05 ± 0.31 and 1.40 ± 0.13, respectively. The optimal time for imaging brain SERT with 4-[ 18 F]-ADAM was 120-140 min after injection. At the optimal imaging time, the SURs (n = 15) in the MB, TH, STR, and PFC were 2.25 ± 0.20, 2.28 ± 0.20, 2.12 ± 0.18 and 1.47 ± 0.14, respectively. There were no significant differences in SERT availability between men and women (p 18 F]-ADAM was safe for human studies and its distribution in human brain appeared to correlate well with the known distribution of SERT in the human brain. In addition, it had high specific binding and a reasonable optimal time for imaging brain SERT in humans. Thus, 4-[ 18 F]-ADAM may be feasible for assessing the status of brain SERT in humans. (orig.)

18F-FDG PET/CT对进展期胃癌治疗前评估的可行性%Feasibility of using 18F-FDG PET/CT for pretherapeutic evaluation of advanced gastric cancer

Institute of Scientific and Technical Information of China (English)

王欣; 于丽娟; 王大龙; 贾承哗; 田墨涵

2009-01-01

目的:探讨18F-FDG PET/C对进展期胃癌治疗前评估的可行性.方法:回顾性分析40例进展期胃癌患者18F-FDG PET/CT常规检查结果资料,与内镜、手术病理和临床随访作对照;其中14例患者行根治性手术,余行化疗或姑息治疗.根据解剖部位将淋巴结分为N1+N2和N3组,淋巴结有无转移以组为单位.原发灶、淋巴结及其他器官转移灶的判断通过目测分析结合标准化摄取值来确定.结果:PET/CT对胃原发癌的灵敏度为97.5%.PET和CT的灵敏度分别为65%和90%;14例根治手术患者N1、N2淋巴结有无转移PET/CT的确诊率为85.7%,灵敏度为71.4%,特异性为77.8%;对N3淋巴结的灵敏度为100%.PET/CT发现21处临床未怀疑的转移灶:PET/CT检查后40%(16/40)的病例分期发生变化.结论:18F-FDG PET/CT可用于进展期胃癌的治疗前评估.

Stress Corrosion cracking susceptibility of reduced-activation martensitic steel F82H

Energy Technology Data Exchange (ETDEWEB)

Miwa, Y. [Nuclear Energy and Science Directorate, Japan Atomic Energy Agency, Tokai-mura, Ibaraki-ken (Japan); Jitsukawa, S.; Tsukada, T. [Japan Atomic Energy Agency, Tokai-mura, Naga-gun, Ibaraki-ken (Japan)

2007-07-01

Full text of publication follows: For fusion power source in near future, supercritical water-cooled type blanket system was planned in Japan Atomic Energy Agency. The blankest system was designed by the present knowledge base and a reasonable extrapolation in material and design technology. Reduced-activation martensitic steel, F82H, is one of the blanket system structural materials. Therefore durability of the F82H for corrosion and stress corrosion cracking (SCC) is one of the concerns for this water-cooling concept of the blanket system. In this paper, SCC susceptibility of F82H was studied after heat treatments simulating post weld heat treatment (PWHT) or neutron-irradiation at 493 K to a dose level of 2.2 dpa. In order to evaluate SCC susceptibility of F82H, slow strain rate testing (SSRT) in high-purity, circulating water was conducted at 513-603 K in an autoclave. The strain rate was 1.0- 2.0x10{sup -7} s{sup -1}. Concentration of dissolved oxygen and hydrogen of the circulating water was controlled by bubbling with these gases. Specimens were heat treated after normalization at 1313 K for 40 min and water quenching. Some of the specimens were tempered at 873-1073 K for 1 h. Since the temperature control during PWHT in vacuum vessel by remote handling will be difficult, it is expected the tempering temperature will be different at place to place. Some specimens after tempering at 1033 K for 1 h were irradiated at 493 K to 2.2 dpa in Japan Research Reactor No.3 at Japan Atomic Energy Agency. The SSRT results showed the as-normalized specimens failed by IGSCC in oxygenated temperature water at 573 K. SSRT results of specimens with other tempering temperature conditions will be presented at conference. In irradiated specimen, IGSCC did not occur in oxygenated water at 5113-603 K. IGSCC also did not occur in hydrogenated water at 573 K. However TGSCC occurred in the irradiated specimen with a round notch (radius= {approx}0.2 mm) in oxygenated water at 573 K

Comparison of {sup 18}F-FET and {sup 18}F-FDG PET in brain tumors

Energy Technology Data Exchange (ETDEWEB)

Pauleit, Dirk; Stoffels, Gabriele [Institute of Neuroscience and Medicine, Forschungszentrum Juelich, D-52425 Juelich (Germany); Bachofner, Ansgar [Clinic of Nuclear Medicine, Heinrich-Heine-University, D-40001 Duesseldorf (Germany); Floeth, Frank W.; Sabel, Michael [Department of Neurosurgery, Heinrich-Heine-University, D-40001 Duesseldorf (Germany); Herzog, Hans; Tellmann, Lutz [Institute of Neuroscience and Medicine, Forschungszentrum Juelich, D-52425 Juelich (Germany); Jansen, Paul [Institute of Advanced Simulation, Forschungszentrum Juelich, D-52425 Juelich (Germany); Reifenberger, Guido [Department of Neuropathology, Heinrich-Heine-University, D-40001 Duesseldorf (Germany); Hamacher, Kurt; Coenen, Heinz H. [Institute of Neuroscience and Medicine, Forschungszentrum Juelich, D-52425 Juelich (Germany); Langen, Karl-Josef [Institute of Neuroscience and Medicine, Forschungszentrum Juelich, D-52425 Juelich (Germany)], E-mail: k.j.langen@fz-juelich.de

2009-10-15

The purpose of this study was to compare the diagnostic value of positron emission tomography (PET) using [{sup 18}F]-fluorodeoxyglucose ({sup 18}F-FDG) and O-(2-[{sup 18}F]fluoroethyl)-L-tyrosine ({sup 18}F-FET) in patients with brain lesions suspicious of cerebral gliomas. Methods: Fifty-two patients with suspicion of cerebral glioma were included in this study. From 30 to 50 min after injection of 180 MBq {sup 18}F-FET, a first PET scan ({sup 18}F-FET scan) was performed. Thereafter, 240 MBq {sup 18}F-FDG was injected and a second PET scan was acquired from 30 to 60 min after the second injection ({sup 18}F-FET/{sup 18}F-FDG scan). The cerebral accumulation of {sup 18}F-FDG was calculated by decay corrected subtraction of the {sup 18}F-FET scan from the {sup 18}F-FET/{sup 18}F-FDG scan. Tracer uptake was evaluated by visual scoring and by lesion-to-background (L/B) ratios. The imaging results were compared with the histological results and prognosis. Results: Histology revealed 24 low-grade gliomas (LGG) of World Health Organization (WHO) Grade II and 19 high-grade gliomas (HGG) of WHO Grade III or IV, as well as nine others, mainly benign histologies. The gliomas showed increased {sup 18}F-FET uptake (>normal brain) in 86% and increased {sup 18}F-FDG uptake (>white matter) in 35%. {sup 18}F-FET PET provided diagnostically useful delineation of tumor extent while this was impractical with {sup 18}F-FDG due to high tracer uptake in the gray matter. A local maximum in the tumor area for biopsy guidance could be identified with {sup 18}F-FET in 76% and with {sup 18}F-FDG in 28%. The L/B ratios showed significant differences between LGG and HGG for both tracers but considerable overlap so that reliable preoperative grading was not possible. A significant correlation of tracer uptake with overall survival was found with {sup 18}F-FDG only. In some benign lesions like abscesses, increased uptake was observed for both tracers indicating a limited specificity of both

Clinically relevant strategies for lowering cardiomyocyte glucose uptake for {sup 18}F-FDG imaging of myocardial inflammation in mice

Energy Technology Data Exchange (ETDEWEB)

Thackeray, James T.; Bankstahl, Jens P.; Bengel, Frank M. [Hanover Medical School, Department of Nuclear Medicine, Hanover (Germany); Wang, Yong; Wollert, Kai C. [Hanover Medical School, Department of Cardiology and Angiology, Hanover (Germany)

2015-04-01

Myocardial inflammation is an emerging target for novel therapies and thus for molecular imaging. Positron emission tomography (PET) with {sup 18}F-fluorodeoxyglucose (FDG) has been employed, but requires an approach for suppression of cardiomyocyte uptake. We tested clinically viable strategies for their suitability in mouse models in order to optimize preclinical imaging protocols. C57BL/6 mice (n = 56) underwent FDG PET under various conditions. In healthy animals, the effect of low-dose (5 units/kg) or high-dose (500 units/kg, 15 min prior) intravenous heparin, extended fasting (18 h) and the impact of conscious injection with limited, late application of isoflurane anaesthesia after 40 min of conscious uptake were examined in comparison to ketamine/xylazine anaesthesia. Conscious injection/uptake strategies were further evaluated at 3 days after permanent coronary artery occlusion. Under continuous isoflurane anaesthesia, neither heparin administration nor extended fasting significantly impacted myocardial {sup 18}F-FDG accumulation. Injection with 40 min uptake in awake mice resulted in a marked reduction of global myocardial {sup 18}F-FDG uptake compared to standard isoflurane anaesthesia (5.7 ± 1.1 %ID/g vs 30.2 ± 7.9 %ID/g, p < 0.01). Addition of heparin and fasting further reduced uptake compared to conscious injection alone (3.8 ± 1.5 %ID/g, p < 0.01) similar to ketamine/xylazine (2.4 ± 2.2 %ID/g, p < 0.001). In the inflammatory phase, 3 days after myocardial infarction, conscious injection/uptake with and without heparin/fasting identified a marked increase in myocardial {sup 18}F-FDG accumulation that was similar to that observed under ketamine/xylazine. Continuous isoflurane anaesthesia obscures any suppressive effect of heparin or fasting on cardiomyocyte glucose utilization. Conscious injection of FDG in rodents significantly reduces cardiomyocyte uptake and enables further suppression by heparin and fasting, similar to clinical observations. In

A novel facile method of labeling octreotide with (18)F-fluorine.

Science.gov (United States)

Laverman, Peter; McBride, William J; Sharkey, Robert M; Eek, Annemarie; Joosten, Lieke; Oyen, Wim J G; Goldenberg, David M; Boerman, Otto C

2010-03-01

Several methods have been developed to label peptides with (18)F. However, in general these are laborious and require a multistep synthesis. We present a facile method based on the chelation of (18)F-aluminum fluoride (Al(18)F) by 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). The method is characterized by the labeling of NOTA-octreotide (NOTA-d-Phe-cyclo[Cys-Phe-d-Trp-Lys-Thr-Cys]-Throl (MH(+) 1305) [IMP466]) with (18)F. Octreotide was conjugated with the NOTA chelate and labeled with (18)F in a 2-step, 1-pot method. The labeling procedure was optimized with regard to the labeling buffer, peptide, and aluminum concentration. Radiochemical yield, specific activity, in vitro stability, and receptor affinity were determined. Biodistribution of (18)F-IMP466 was studied in AR42J tumor-bearing mice and compared with that of (68)Ga-labeled IMP466. In addition, small-animal PET/CT images were acquired. IMP466 was labeled with Al(18)F in a single step with 50% yield. The labeled product was purified by high-performance liquid chromatography to remove unbound Al(18)F and unlabeled peptide. The radiolabeling, including purification, was performed in 45 min. The specific activity was 45,000 GBq/mmol, and the peptide was stable in serum for 4 h at 37 degrees C. Labeling was performed at pH 4.1 in sodium citrate, sodium acetate, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, and 2-(N-morpholino)ethanesulfonic acid buffer and was optimal in sodium acetate buffer. The apparent 50% inhibitory concentration of the (19)F-labeled IMP466 determined on AR42J cells was 3.6 nM. Biodistribution studies at 2 h after injection showed a high tumor uptake of (18)F-IMP466 (28.3 +/- 5.2 percentage injected dose per gram [%ID/g]; tumor-to-blood ratio, 300 +/- 90), which could be blocked by an excess of unlabeled peptide (8.6 +/- 0.7 %ID/g), indicating that the accumulation in the tumor was receptor-mediated. Biodistribution of (68)Ga-IMP466 was similar to that of (18)F-IMP466. (18)F

A simplified one-pot synthesis of 9-[(3-[18F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F]FHPG) and 9-(4-[18F]Fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) for gene therapy

International Nuclear Information System (INIS)

Shiue, Grace G.; Shiue, Chyng-Yann; Lee, Roland L.; MacDonald, Douglas; Hustinx, Roland; Eck, Stephen L.; Alavi, Abass A.

2001-01-01

9-[(3-[ 18 F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([ 18 F]FHPG, 2) has been synthesized by nucleophilic substitution of N 2 -(p-anisyldiphenylmethyl)-9-{[1-(p-anisyldiphenylmethoxy)-3 -toluenesulfonyloxy-2-propoxy]methyl}guanine (1) with potassium [ 18 F]fluoride/Kryptofix 2.2.2 followed by deprotection with 1 N HCl and purification with different methods in variable yields. When both the nucleophilic substitution and deprotection were carried out at 90 deg. C and the product was purified by HPLC (method A), the yield of compound 2 was 5-10% and the synthesis time was 90 min from EOB. However, if both the nucleophilic substitution and deprotection were carried out at 120 deg. C and the product was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2 was synthesized at 90 deg. C and purified by Silica Sep-Pak (method B), the yield increased to 10-15% and the synthesis time was 60 min from EOB. Similarly, 9-(4-[ 18 F]fluoro-3-hydroxymethylbutyl)guanine ([ 18 F]FHBG, 4) was synthesized with method A and method B in 9% and 10-15% yield, respectively, in a synthesis time of 90 and 60 min, respectively, from EOB. Compound 2 was relatively unstable in acidic medium at 120 deg. C while compound 4 was stable under the same condition. Both compound 2 and compound 4 had low lipid/water partition coefficient (0.126±0.022, n=5 and 0.165±0.023, n=5, respectively). Although it contains non-radioactive ganciclovir (∼5-30 μg) as a chemical by-product, compound 2 synthesized by method B has a similar uptake in 9L glioma cells as that synthesized by method A, and is a potential tracer for imaging herpes simplex virus thymidine kinase gene expression in tumors using PET. Similarly, compound 4 synthesized by method B contains ∼10-25 μg of penciclovir as a chemical by-product. Thus, the simplified one pot synthesis (method B) is a useful method for synthesizing both compound 2 and compound 4 in good yield for routine clinical use, and the method is

Sulfonyl fluoride-based prosthetic compounds as potential 18F labelling agents.

Science.gov (United States)

Inkster, James A H; Liu, Kate; Ait-Mohand, Samia; Schaffer, Paul; Guérin, Brigitte; Ruth, Thomas J; Storr, Tim

2012-08-27

Nucleophilic incorporation of [(18)F]F(-) under aqueous conditions holds several advantages in radiopharmaceutical development, especially with the advent of complex biological pharmacophores. Sulfonyl fluorides can be prepared in water at room temperature, yet they have not been assayed as a potential means to (18)F-labelled biomarkers for PET chemistry. We developed a general route to prepare bifunctional 4-formyl-, 3-formyl-, 4-maleimido- and 4-oxylalkynl-arylsulfonyl [(18)F]fluorides from their sulfonyl chloride analogues in 1:1 mixtures of acetonitrile, THF, or tBuOH and Cs[(18)F]F/Cs(2)CO(3(aq.)) in a reaction time of 15 min at room temperature. With the exception of 4-N-maleimide-benzenesulfonyl fluoride (3), pyridine could be used to simplify radiotracer purification by selectively degrading the precursor without significantly affecting observed yields. The addition of pyridine at the start of [(18)F]fluorination (1:1:0.8 tBuOH/Cs(2)CO(3(aq.))/pyridine) did not negatively affect yields of 3-formyl-2,4,6-trimethylbenzenesulfonyl [(18)F]fluoride (2) and dramatically improved the yields of 4-(prop-2-ynyloxy)benzenesulfonyl [(18)F]fluoride (4). The N-arylsulfonyl-4-dimethylaminopyridinium derivative of 4 (14) can be prepared and incorporates (18)F efficiently in solutions of 100 % aqueous Cs(2)CO(3) (10 mg mL(-1)). As proof-of-principle, [(18)F]2 was synthesised in a preparative fashion [88(±8) % decay corrected (n=6) from start-of-synthesis] and used to radioactively label an oxyamino-modified bombesin(6-14) analogue [35(±6) % decay corrected (n=4) from start-of-synthesis]. Total preparation time was 105-109 min from start-of-synthesis. Although the (18)F-peptide exhibited evidence of proteolytic defluorination and modification, our study is the first step in developing an aqueous, room temperature (18)F labelling strategy. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ammonium iron(III phosphate(V fluoride, (NH40.5[(NH40.375K0.125]FePO4F, with ammonium partially substituted by potassium

Directory of Open Access Journals (Sweden)

Lei Wang

2009-01-01

Full Text Available The title compound, ammonium potassium iron(III phosphate fluoride, (NH40.875K0.125FePO4F, is built from zigzag chains ∞1{[FeO4F2]7−}, with Fe3+ in a distorted octahedral coordination, extending along both the [011] and [0overline{1}1] directions. These chains are made up of alternating trans-[FeO4F2] and cis-[FeO4F2] octahedra via shared F-atom corners, and are linked by PO4 tetrahedra, resulting in an open-framework structure with channels along the [010] and [100] directions. There are two crystallographically independent ammonium sites: one in the [010] channels and the other, partially substituted by K+ ions, in the [100] channels. The ammonium in the [010] channels is fixed to the framework via eight hydrogen bonds (six N—H...O and two N—H...F.

Synthesis and Monkey-PET Study of (R)- and (S)-18F-Labeled 2-Arylbenzoheterocyclic Derivatives as Amyloid Probes with Distinctive in Vivo Kinetics.

Science.gov (United States)

Yang, Yanping; Wang, Xuedan; Yang, Hui; Fu, Hualong; Zhang, Jinming; Zhang, Xiaojun; Dai, Jiapei; Zhang, Zhiyong; Lin, Chunping; Guo, Yuzhi; Cui, Mengchao

2016-11-07

This study describes an effective strategy to improve pharmacokinetics of Aβ imaging agents, offering a novel class of (R)- and (S)- 18 F-labeled 2-arylbenzoheterocyclic derivatives which bear an additional chiral hydroxyl group on the side chain. These ligands displayed binding abilities toward Aβ aggregates with K i values ranging from 3.2 to 195.6 nM. Chirality-related discrepancy was observed in biodistribution, and (S)-2-phenylbenzoxazole enantiomers exhibited vastly improved brain clearance with washout ratios higher than 20. Notably, (S)-[ 18 F]28 possessed high binding potency (K i = 7.6 nM) and exceptional brain kinetics (9.46% ID/g at 2 min, brain 2min /brain 60min = 27.8) that is superior to well-established [ 18 F]AV45. The excellent pharmacokinetics and low nonspecific binding of (S)-[ 18 F]28 were testified by dynamic PET/CT scans in monkey brains. In addition, (S)-[ 18 F]28 clearly labeled Aβ plaques both in vitro and ex vivo. These results might qualify (S)-[ 18 F]28 to detect Aβ plaques with high signal-to-noise ratio.

Hydrogen permeation measurement of the reduced activation ferritic steel F82H by the vacuum thermo-balance method

International Nuclear Information System (INIS)

Yoshida, Hajime; Enoeda, Mikio; Abe, Tetsuya; Akiba, Masato

2005-03-01

Hydrogen permeation fluxes of the reduced activation ferritic steel F82H were quantitatively measured by a newly proposed method, vacuum thermo-balance method, for a precise estimation of tritium leakage in a fusion reactor. We prepared sample capsules made of F82H, which enclosed hydrogen gas. The hydrogen in the capsules permeated through the capsule wall, and subsequently desorbed from the capsule surface during isothermal heating. The vacuum thermo-balance method allows simultaneous measurement of the hydrogen permeation flux by two independent methods, namely, the net weight reduction of the sample capsule and exhaust gas analysis. Thus the simultaneous measurements by two independent methods increase the reliability of the permeability measurement. When the gas pressure of enclosed hydrogen was 0.8 atm at the sample temperature of 673 K, the hydrogen permeation flux of F82H obtained by the net weight reduction and the exhaust gas analysis was 0.75x10 18 (H 2 /m 2 s) and 2.2x10 18 (H 2 /m 2 s), respectively. The ratio of the hydrogen permeation fluxes obtained by the net weight reduction to that measured by the exhaust gas analysis was in the range from 1/4 to 1/1 in this experiment. The temperature dependence of the estimated permeation flux was similar in both methods. Taking the uncertainties of both measurements into consideration, both results are supposed to be consistent. The enhancement of hydrogen permeation flux was observed from the sample of which outer surface was mechanically polished. Through the present experiments, it has been demonstrated that the vacuum thermo-balance method is effective for the measurement of hydrogen permeation rate of F82H. (author)

Positron emission tomography imaging of the 18-kDa translocator protein (TSPO) with [18F]FEMPA in Alzheimer's disease patients and control subjects

International Nuclear Information System (INIS)

Varrone, Andrea; Oikonen, Vesa; Joutsa, Juho; Solin, Olof; Haaparanta-Solin, Merja; Rinne, Juha O.; Forsberg, Anton; Takano, Akihiro; Nag, Sangram; Nakao, Ryuji; Halldin, Christer; Al-Tawil, Nabil; Wells, Lisa A.; Rabiner, Eugenii A.; Valencia, Ray; Schultze-Mosgau, Marcus; Thiele, Andrea; Vollmer, Sonja; Dyrks, Thomas; Lehmann, Lutz; Heinrich, Tobias; Hoffmann, Anja; Nordberg, Agneta

2015-01-01

Imaging of the 18-kDa translocator protein (TSPO) is a potential tool for examining microglial activation and neuroinflammation in early Alzheimer's disease (AD). [ 18 F]FEMPA is a novel high-affinity second-generation TSPO radioligand that has displayed suitable pharmacokinetic properties in preclinical studies. The aims of this study were to quantify the binding of [ 18 F]FEMPA to TSPO in AD patients and controls and to investigate whether higher [ 18 F]FEMPA binding in AD patients than in controls could be detected in vivo. Ten AD patients (five men, five women; age 66.9 ± 7.3 years; MMSE score 25.5 ± 2.5) and seven controls (three men, four women; age 63.7 ± 7.2 years, MMSE score 29.3 ± 1.0) were studied using [ 18 F]FEMPA at Turku (13 subjects) and at Karolinska Institutet (4 subjects). The in vitro binding affinity for TSPO was assessed using PBR28 in a competition assay with [ 3 H]PK11195 in seven controls and eight AD patients. Cortical and subcortical regions of interest were examined. Quantification was performed using a two-tissue compartment model (2TCM) and Logan graphical analysis (GA). The outcome measure was the total distribution volume (V T ). Repeated measures analysis of variance was used to assess the effect of group and TSPO binding status on V T . Five AD patients and four controls were high-affinity binders (HABs). Three AD patients and three controls were mixed-affinity binders. V T estimated with Logan GA was significantly correlated with V T estimated with the 2TCM in both controls (r = 0.97) and AD patients (r = 0.98) and was selected for the final analysis. Significantly higher V T was found in the medial temporal cortex in AD patients than in controls (p = 0.044) if the TSPO binding status was entered as a covariate. If only HABs were included, significantly higher V T was found in the medial and lateral temporal cortex, posterior cingulate, caudate, putamen, thalamus and cerebellum in AD patients than in controls (p 18 F

Interests of the PET with 18-F.D.G. in infectious pathology: about a case of systemic candidiasis; Interets de la TEP au 18-FDG en pathologie infectieuse: a propos d'un cas de candidose systemique

Energy Technology Data Exchange (ETDEWEB)

Avet, J.; Granjon, D.; Prevot, N.; Isnardi, V.; Dubois, F. [Service de medecine nucleaire, CHU de Saint-etienne, (France); Stephan, J.L.; Berger, C. [service de pediatrie, CHU de Saint-etienne, (France)

2009-05-15

We report the interest of the PET with {sup 18}F-F.D.G. in the extension evaluation of injuries and in the therapy decision for a patient suffering of a systemic candida. Conclusions: In spite of a lack of recommendations, because of its great sensitivity for the deep infectious centres detection, the PET with {sup 18}F-F.D.G. can bring useful information to the management and follow up of the systemic infections. (N.C.)

Activity concentration and AACED due to 40K in some selected medicinal plants

International Nuclear Information System (INIS)

Chandrashekara, K.; Radhakrishna, A.P.; Somashekarappa, H.M.

2017-01-01

The activity concentrations in soil and medicinal plants, soil to plant transfer factors (TF), and Average Annual Committed Effective Dose (AACED) of 40 K in prominent medicinal plants of Malnad Kerala were estimated. The range of activity concentrations were 144.15 - 558.99 and 405.87 - 2990.75 Bq kg -1 in soil and medicinal plants respectively. The TF was found to vary from 2.34 to 14.84, whereas AACED varied in the range 2.51 - 18.54 mSv y -1 . The study may help to form the database and safety regulations connected with 40 K activity in medicinal plants. (author)

Setting up an apparatus for routine preparation of [18F]FDG

International Nuclear Information System (INIS)

Fuechtner, F.; Steinbach, J.; Loesel, E.; Luecke, R.

1994-01-01

The most widely used radiopharmaceutical in positron emission tomography (PET) studies is 2-[ 18 F]fluoro-2-deoxy-D-glucose ([ 18 F]FDG). The [ 18 F]FDG-preparation device consists of two main parts, the processing unit, situated inside the hot cell and its control unit. A pump, the radiation monitors and a recorder are additionally used. All parts of the processing unit, such as the reaction vessel, purification columns, electro-magnetic and electric stream selection valves, fittings, tubes, a waste absorber, electrical and tube connectors, conductivity cells, radioactivity monitors (Geiger-Mueller tubes, 70034, VacuTec) and the manometer, are mounted on a stainless steel housing. The processing unit is remote controlled by the control unit via a common 24-wire cabel. The tubes for the target gas, the compressed N 2 (for delivering the liquids), and the vessels containing the liquids needed for the synthesis, are connected to the synthesis unit by PTFE tubing and luer adapters. (orig./EF)

Novel Feshbach resonances in a ^40K spin-mixture

Science.gov (United States)

Walraven, J. T. M.; Ludewig, A.; Tiecke, T. G.

2010-03-01

We present experimental results on novel s-wave Feshbach resonances in ^40K spin-mixtures. Using an extended version of the Asymptotic Bound-state Model (ABM) [1] we predict Feshbach resonances with more promising characteristics than the commonly used resonances in the (|F,mF>) |9/2,-9/2>+|9/2,-7/2> and |9/2,-9/2>+|9/2,-5/2> spin mixtures. We report on an s-wave resonance in the |9/2,-5/2>+|9/2,-3/2> mixture. We have experimentally observed the corresponding loss-feature at B0˜178 G with a width of ˜10G. This resonance is promising due to its large predicted width and the absence of an overlapping p-wave resonance. We present our recent results on measurements of the resonance width and the stability of the system around this and other observed s-wave and p-wave resonances. [4pt] [1] T.G. Tiecke, et al., Phys. Rev. Lett. 104, 053202 (2010).

Localization of [18F]fluorodeoxyglucose in mouse brain neurons with micro-autoradiography

International Nuclear Information System (INIS)

Yamada, Susumu; Kubota, Roko; Kubota, Kazuo; Ishiwata, Kiichi; Ido, Tatsuo

1990-01-01

This is the first study of micro-autoradiography (micro-ARG) for [ 18 F]2-fluoro-2-deoxy-D-glucose ([ 18 F]FDG). The localization of [ 18 F]FDG was demonstrated in dendrites of neuron and also in the myelinated axon in mouse normal brain in vivo. The nucleolus was relatively free of label. The counted silver grain numbers in autoradiogram were linearly correlated to the 18 F radioactivities in the specimen. The micro-ARG using positron emitting 18 F is a very time-saving technique with 4 hours exposure compared with the conventional method using 3 H- or 14 C-labelled tracers. (author)

Determination of $f_s/f_d$ for 7 TeV $pp$ collisions and a measurement of the branching fraction of the decay $B^0 \\to D^{-}K^{+}$

CERN Document Server

Aaij, R; Adinolfi, M; Adrover, C; Affolder, A; Ajaltouni, Z; Albrecht, J; Alessio, F; Alexander, M; Alkhazov, G; Alvarez Cartelle, P; Alves Jr, A A; Amato, S; Amhis, Y; Amoraal, J; Anderson, J; Appleby, R B; Aquines Gutierrez, O; Arrabito, L; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Bachmann, S; Back, J J; Bailey, D S; Balagura, V; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Bates, A; Bauer, C; Bauer, Th; Bay, A; Bediaga, I; Belous, K; Belyaev, I; Ben-Haim, E; Benayoun, M; Bencivenni, G; Benson, S; Benton, J; Bernet, R; Bettler, M O; van Beuzekom, M; Bien, A; Bifani, S; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blanks, C; Blouw, J; Blusk, S; Bobrov, A; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Bowcock, T J V; Bozzi, C; Brambach, T; van den Brand, J; Bressieux, J; Brisbane, S; Britsch, M; Britton, T; Brook, N H; Büchler-Germann, A; Bursche, A; Buytaert, J; Cadeddu, S; Carvajal, J.M.Caicedo; Callot, O; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carson, L; Carvalho Akiba, K; Casse, G; Cattaneo, M; Charles, M; Charpentier, Ph; Chiapolini, N; Cid Vidal, X; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coca, C; Coco, V; Cogan, J; Collins, P; Constantin, F; Conti, G; Contu, A; Cook, A; Coombes, M; Corti, G; Cowan, G A; Currie, R; D'Almagne, B; D'Ambrosio, C; David, P; David, P N Y; De Bonis, I; De Capua, S; De Cian, M; De Lorenzi, F; De Miranda, J M; De Paula, L; De Simone, P; Decamp, D; Deckenhoff, M; Degaudenzi, H; Deissenroth, M; Del Buono, L; Deplano, C; Deschamps, O; Dettori, F; Dickens, J; Dijkstra, H; Diniz Batista, P; Dossett, D; Dovbnya, A; Dupertuis, F; Dzhelyadin, R; Eames, C; Easo, S; Egede, U; Egorychev, V; Eidelman, S; van Eijk, D; Eisele, F; Eisenhardt, S; Ekelhof, R; Eklund, L; Elsasser, Ch; d'Enterria, D G; Esperante Pereira, D; Esteve, L; Falabella, A; Fanchini, E; Farber, C; Fardell, G; Farinelli, C; Farry, S; Fave, V; Fernandez Albor, V; Ferro-Luzzi, M; Filippov, S; Fitzpatrick, C; Fontana, M; Fontanelli, F; Forty, R; Frank, M; Frei, C; Frosini, M; Furcas, S; Gallas Torreira, A; Galli, D; Gandelman, M; Gandini, P; Gao, Y; Garnier, J-C; Garofoli, J; Garrido, L; Gaspar, C; Gauvin, N; Gersabeck, M; Gershon, T; Ghez, Ph; Gibson, V; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gordon, H; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graziani, G; Grecu, A; Gregson, S; Gui, B; Gushchin, E; Guz, Yu; Gys, T; Haefeli, G; Haines, S C; Hampson, T; Hansmann-Menzemer, S; Harji, R; Harnew, N; Harrison, J; Harrison, P F; He, J; Heijne, V; Hennessy, K; Henrard, P; Hernando Morata, J A; van Herwijnen, E; Hofmann, W; Holubyev, K; Hopchev, P; Hulsbergen, W; Hunt, P; Huse, T; Huston, R S; Hutchcroft, D; Hynds, D; Iakovenko, V; Ilten, P; Imong, J; Jacobsson, R; Jahjah Hussein, M; Jans, E; Jansen, F; Jaton, P; Jean-Marie, B; Jing, F; John, M; Johnson, D; Jones, C R; Jost, B; Kandybei, S; Karbach, T M; Keaveney, J; Kerzel, U; Ketel, T; Keune, A; Khanji, B; Kim, Y M; Knecht, M; Koblitz, S; Koppenburg, P; Kozlinskiy, A; Kravchuk, L; Kreplin, K; Krocker, G; Krokovny, P; Kruse, F; Kruzelecki, K; Kucharczyk, M; Kukulak, S; Kumar, R; Kvaratskheliya, T; La Thi, V N; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lambert, R W; Lanciotti, E; Lanfranchi, G; Langenbruch, C; Latham, T; Le Gac, R; van Leerdam, J; Lees, J P; Lefèvre, R; Leflat, A; Lefrancois, J; Leroy, O; Lesiak, T; Li, L; Li, Y Y; Li Gioi, L; Lieng, M; Lindner, R; Linn, C; Liu, B; Liu, G; Lopes, J H; Lopez Asamar, E; Lopez-March, N; Luisier, J; Machefert, F; Machikhiliyan, I V; Maciuc, F; Maev, O; Magnin, J; Maier, A; Malde, S; Mamunur, R M D; Manca, G; Mancinelli, G; Mangiafave, N; Marconi, U; Märki, R; Marks, J; Martellotti, G; Martens, A; Martin, L; Martín Sánchez, A; Martinez Santos, D; Massafferri, A; Mathe, Z; Matteuzzi, C; Matveev, M; Maurice, E; Maynard, B; Mazurov, A; McGregor, G; McNulty, R; Mclean, C; Meissner, M; Merk, M; Merkel, J; Messi, R; Miglioranzi, S; Milanes, D A; Minard, M N; Monteil, S; Moran, D; Morawski, P; Morris, J V; Mountain, R; Mous, I; Muheim, F; Muller, K; Muresan, R; Muryn, B; Musy, M; Naik, P; Nakada, T; Nandakumar, R; Nardulli, J; Nedos, M; Needham, M; Neufeld, N; Nguyen-Mau, C; Nicol, M; Nies, S; Niess, V; Nikitin, N; Oblakowska-Mucha, A; Obraztsov, V; Oggero, S; Ogilvy, S; Okhrimenko, O; Oldeman, R; Orlandea, M; Otalora Goicochea, J M; Pal, B; Palacios, J; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Parkes, C; Parkinson, C J; Passaleva, G; Patel, G D; Patel, M; Paterson, S K; Patrick, G N; Patrignani, C; Pavel-Nicorescu, C; Pazos Alvarez, A; Pellegrino, A; Penso, G; Pepe Altarelli, M; Perazzini, S; Perego, D L; Perez Trigo, E; Pérez-Calero Yzquierdo, A; Perret, P; Perrin-Terrin, M; Pessina, G; Petrella, A; Petrolini, A; Pie Valls, B; Pietrzyk, B; Pilar, T; Pinci, D; Plackett, R; Playfer, S; Plo Casasus, M; Polok, G; Poluektov, A; Polycarpo, E; Popov, D; Popovici, B; Potterat, C; Powell, A; du Pree, T; Pugatch, V; Puig Navarro, A; Qian, W; Rademacker, J H; Rakotomiaramanana, B; Raniuk, I; Raven, G; Redford, S; Reid, M M; dos Reis, A C; Ricciardi, S; Rinnert, K; Romero, D.A.Roa; Robbe, P; Rodrigues, E; Rodrigues, F; Rodriguez Cobo, C; Rodriguez Perez, P; Rogers, G J; Romanovsky, V; Rouvinet, J; Ruf, T; Ruiz, H; Sabatino, G; Saborido Silva, J J; Sagidova, N; Sail, P; Saitta, B; Salzmann, C; Sannino, M; Santacesaria, R; Santinelli, R; Santovetti, E; Sapunov, M; Sarti, A; Satriano, C; Satta, A; Savrie, M; Savrina, D; Schaack, P; Schiller, M; Schleich, S; Schmelling, M; Schmidt, B; Schneider, O; Schopper, A; Schune, M H; Schwemmer, R; Sciubba, A; Seco, M; Semennikov, A; Senderowska, K; Serra, N; Serrano, J; Seyfert, P; Shao, B; Shapkin, M; Shapoval, I; Shatalov, P; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, O; Shevchenko, V; Shires, A; Silva Coutinho, R; Skottowe, H P; Skwarnicki, T; Smith, A C; Smith, N A; Sobczak, K; Soler, F J P; Solomin, A; Soomro, F; Souza De Paula, B; Spaan, B; Sparkes, A; Spradlin, P; Stagni, F; Stahl, S; Steinkamp, O; Stoica, S; Stone, S; Storaci, B; Straumann, U; Styles, N; Swientek, S; Szczekowski, M; Szczypka, P; Szumlak, T; T'Jampens, S; Teodorescu, E; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Topp-Joergensen, S; Tran, M T; Tsaregorodtsev, A; Tuning, N; Ukleja, A; Urquijo, P; Uwer, U; Vagnoni, V; Valenti, G; Vazquez Gomez, R; Vazquez Regueiro, P; Vecchi, S; Velthuis, J J; Veltri, M; Vervink, K; Viaud, B; Videau, I; Vilasis-Cardona, X; Visniakov, J; Vollhardt, A; Voong, D; Vorobyev, A; Voss, H; Wacker, K; Wandernoth, S; Wang, J; Ward, D R; Webber, A D; Websdale, D; Whitehead, M; Wiedner, D; Wiggers, L; Wilkinson, G; Williams, M P; Williams, M; Wilson, F F; Wishahi, J; Witek, M; Witzeling, W; Wotton, S A; Wyllie, K; Xie, Y; Xing, F; Yang, Z; Young, R; Yushchenko, O; Zavertyaev, M; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhong, L; Zverev, E; Zvyagin, A

2011-01-01

The relative abundance of the three decay modes $B^0 \\to D^- K^+$, $B^0 \\to D^- \\pi^+$ and $B^0_s \\to D_s^- \\pi^+$ produced in 7 TeV $pp$ collisions at the LHC is determined from data corresponding to an integrated luminosity of 35 pb$^{-1}$. The branching fraction of $B^0 \\to D^- K^+$ is found to be $\\cal B (B^0 \\to D^- K^+) = (2.01 \\pm 0.18^{\\textrm{stat}} \\pm 0.14^{\\textrm{syst}})\\times 10^{-4}$. The ratio of fragmentation fractions $f_s/f_d$ is determined through the relative abundance of $B^0_s \\to D_s^- \\pi^+$ to $B^0 \\to D^- K^+$ and $B^0 \\to D^-\\pi^+$, leading to $f_s/f_d = 0.253 \\pm 0.017 \\pm 0.017 \\pm 0.020$, where the uncertainties are statistical, systematic, and theoretical respectively.

Quantitative PET Imaging of Tissue Factor Expression Using 18F-Labeled Active Site-Inhibited Factor VII.

Science.gov (United States)

Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E; Jensen, Mette M; Kristensen, Lotte K; Madsen, Jacob; Petersen, Lars C; Kjaer, Andreas

2016-01-01

Tissue factor (TF) is upregulated in many solid tumors, and its expression is linked to tumor angiogenesis, invasion, metastasis, and prognosis. A noninvasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII is the natural ligand to TF. Here we report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of factor VII. Active site-inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4-(18)F-fluorobenzoate and purified. The corresponding product, (18)F-FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small-animal PET/CT imaging 1, 2, and 4 h after injection. Ex vivo biodistribution was performed after the last imaging session, and tumor tissue was preserved for molecular analysis. A blocking experiment was performed in a second set of mice. The expression pattern of TF in the tumors was visualized by immunohistochemistry and the amount of TF in tumor homogenates was measured by enzyme-linked immunosorbent assay and correlated with the uptake of (18)F-FVIIai in the tumors measured in vivo by PET imaging. The PET images showed high uptake of (18)F-FVIIai in the tumor regions, with a mean uptake of 2.5 ± 0.3 percentage injected dose per gram (%ID/g) (mean ± SEM) 4 h after injection of 7.3-9.3 MBq of (18)F-FVIIai and with an average maximum uptake in the tumors of 7.1 ± 0.7 %ID/g at 4 h. In comparison, the muscle uptake was 0.2 ± 0.01 %ID/g at 4 h. At 4 h, the tumors had the highest uptake of any organ. Blocking with FVIIai significantly reduced the uptake of (18)F-FVIIai from 2.9 ± 0.1 to 1.4 ± 0.1 %ID/g (P < 0.001). The uptake of (18)F-FVIIai measured in vivo by PET imaging correlated (r = 0.72, P < 0.02) with TF protein level measured ex vivo. (18)F-FVIIai is a promising PET tracer for

Comparative assessment of 6-[18 F]fluoro-L-m-tyrosine and 6-[18 F]fluoro-L-dopa to evaluate dopaminergic presynaptic integrity in a Parkinson's disease rat model.

Science.gov (United States)

Becker, Guillaume; Bahri, Mohamed Ali; Michel, Anne; Hustadt, Fabian; Garraux, Gaëtan; Luxen, André; Lemaire, Christian; Plenevaux, Alain

2017-05-01

Because of the progressive loss of nigro-striatal dopaminergic terminals in Parkinson's disease (PD), in vivo quantitative imaging of dopamine (DA) containing neurons in animal models of PD is of critical importance in the preclinical evaluation of highly awaited disease-modifying therapies. Among existing methods, the high sensitivity of positron emission tomography (PET) is attractive to achieve that goal. The aim of this study was to perform a quantitative comparison of brain images obtained in 6-hydroxydopamine (6-OHDA) lesioned rats using two dopaminergic PET radiotracers, namely [ 18 F]fluoro-3,4-dihydroxyphenyl-L-alanine ([ 18 F]FDOPA) and 6-[ 18 F]fluoro-L-m-tyrosine ([ 18 F]FMT). Because the imaging signal is theoretically less contaminated by metabolites, we hypothesized that the latter would show stronger relationship with behavioural and post-mortem measures of striatal dopaminergic deficiency. We used a within-subject design to measure striatal [ 18 F]FMT and [ 18 F]FDOPA uptake in eight partially lesioned, eight fully lesioned and ten sham-treated rats. Animals were pretreated with an L-aromatic amino acid decarboxylase inhibitor. A catechol-O-methyl transferase inhibitor was also given before [ 18 F]FDOPA PET. Quantitative estimates of striatal uptake were computed using conventional graphical Patlak method. Striatal dopaminergic deficiencies were measured with apomorphine-induced rotations and post-mortem striatal DA content. We observed a strong relationship between [ 18 F]FMT and [ 18 F]FDOPA estimates of decreased uptake in the denervated striatum using the tissue-derived uptake rate constant K c . However, only [ 18 F]FMT K c succeeded to discriminate between the partial and the full 6-OHDA lesion and correlated well with the post-mortem striatal DA content. This study indicates that the [ 18 F]FMT could be more sensitive, with respect of [ 18 F]FDOPA, to investigate DA terminals loss in 6-OHDA rats, and open the way to in vivo L

Comparison of five cluster validity indices performance in brain [18 F]FET-PET image segmentation using k-means.

Science.gov (United States)

Abualhaj, Bedor; Weng, Guoyang; Ong, Melissa; Attarwala, Ali Asgar; Molina, Flavia; Büsing, Karen; Glatting, Gerhard

2017-01-01

Dynamic [ 18 F]fluoro-ethyl-L-tyrosine positron emission tomography ([ 18 F]FET-PET) is used to identify tumor lesions for radiotherapy treatment planning, to differentiate glioma recurrence from radiation necrosis and to classify gliomas grading. To segment different regions in the brain k-means cluster analysis can be used. The main disadvantage of k-means is that the number of clusters must be pre-defined. In this study, we therefore compared different cluster validity indices for automated and reproducible determination of the optimal number of clusters based on the dynamic PET data. The k-means algorithm was applied to dynamic [ 18 F]FET-PET images of 8 patients. Akaike information criterion (AIC), WB, I, modified Dunn's and Silhouette indices were compared on their ability to determine the optimal number of clusters based on requirements for an adequate cluster validity index. To check the reproducibility of k-means, the coefficients of variation CVs of the objective function values OFVs (sum of squared Euclidean distances within each cluster) were calculated using 100 random centroid initialization replications RCI 100 for 2 to 50 clusters. k-means was performed independently on three neighboring slices containing tumor for each patient to investigate the stability of the optimal number of clusters within them. To check the independence of the validity indices on the number of voxels, cluster analysis was applied after duplication of a slice selected from each patient. CVs of index values were calculated at the optimal number of clusters using RCI 100 to investigate the reproducibility of the validity indices. To check if the indices have a single extremum, visual inspection was performed on the replication with minimum OFV from RCI 100 . The maximum CV of OFVs was 2.7 × 10 -2 from all patients. The optimal number of clusters given by modified Dunn's and Silhouette indices was 2 or 3 leading to a very poor segmentation. WB and I indices suggested in

Production of PET radiopharmaceutical 18F-FDG using synthesizer automatic module

International Nuclear Information System (INIS)

Purwoko; Chairuman; Adang Hardi Gunawan; Yayan Tahyan; Eny Lestari; Sri Aguswarini Lestiyowati; Karyadi; Sri Bagiawati

2010-01-01

Radiopharmaceutical 2-( 18 F)Fluoro-2-Deoxy-D-Glucose or 18 F(FDG) is an important PET (Positron Emission Tomography) radiopharmaceutical for tumour imaging. In the PET technique glucose metabolism in tumour tissues can be determined quantitatively and used for diagnosis staging and monitoring of treatment tumour or cancer disease in medical oncology. The production of 2-( 18 F)Fluoro-2-Deoxy-D-Glucose 18 F-FDG using compact automated system module TRACERlab MX has been carried out. The modular setup of the apparatus permits reliable for routine synthesis of radiopharmaceuticals 18 F-FDG based on kriptofix mediated nucleophilic fluorination to mannose triflate precursor. Radiochemical yield of 18 F-FDG was 53.895 % (decay time uncorrected) in 40 minutes. The product showed that the colorless and clear solution at pH:6, sterile and pirogen free, kriptofix impurities was low and radiochemical purity was 99.595%. (author)

Evaluation of {sup 18}F-FDG and {sup 18}F-FLT for monitoring therapeutic responses of colorectal cancer cells to radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Wang, Hui [Nuclear Medicine Department, The General Hospital of the Chinese People' s Liberation Army and Military Medical Postgraduate College, Beijing 100853 (China); Liu, Bo [Department of Hepatobiliary Surgery, The General Hospital of the Chinese People' s Liberation Army and Military Medical Postgraduate College, Beijing 100853 (China); Tian, Jiahe, E-mail: tianjh@vip.sina.com [Nuclear Medicine Department, The General Hospital of the Chinese People' s Liberation Army and Military Medical Postgraduate College, Beijing 100853 (China); Xu, Baixuan; Zhang, Jinming [Nuclear Medicine Department, The General Hospital of the Chinese People' s Liberation Army and Military Medical Postgraduate College, Beijing 100853 (China); Qu, Baolin [Department of Radiation Oncology, The General Hospital of the Chinese People' s Liberation Army and Military Medical Postgraduate College, Beijing 100853 (China); Chen, Yingmao [Nuclear Medicine Department, The General Hospital of the Chinese People' s Liberation Army and Military Medical Postgraduate College, Beijing 100853 (China)

2013-09-15

In order to compare the efficacy of {sup 18}F-fluorothymidine (FLT) and {sup 18}F-fluorodeoxyglucose (FDG) for monitoring early responses to irradiation, two human colorectal cancer (CRC) cell lines SW480 and SW620, which were derived from the primary lesions and the metastatic lymph node, underwent X-ray irradiation of 0, 10, or 20 Gy and were examined at 0, 24 and 72 h After irradiation, reduced proliferation of both SW480 and SW620 cells was observed in a dose-dependent manner (P < 0.001), G0-G1 arrest was also noted in both cell types after 72 h in the 20 Gy group (P < 0.001). Although increased apoptosis was observed in both cell lines after irradiation (P < 0.001), a greater percentage of SW480 cells underwent apoptosis in response to irradiation than SW620 cells. Increased Hsp27 and decreased integrin β{sub 3}, Ki67 and VEGFR2 expression was observed over time via immunocytochemistry and Western blot analysis (P < 0.001), however, no significant changes were noted in response to irradiation. Finally, reduced uptake of {sup 18}F-FLT by SW480 or SW620 cells was observed at 24-h post-irradiation, however, reduced {sup 18}F-FDG uptake was only observed after 72 h. Therefore, we conclude that {sup 18}F-FLT is a more suitable positron emission tomography (PET) tracer for monitoring early responses to irradiation in primary and metastatic lymph node CRC cells.

Influence of traps on the deuterium behaviour in the low activation martensitic steels F82H and Batman

International Nuclear Information System (INIS)

Serra, E.

1997-01-01

A time dependent permeation method is used to measure the permeability, diffusivity and solubility of deuterium in the low activation martensitic steels F82H and Batman. The measurements cover the temperature range from 373 to 743 K which includes the onset of deuterium trapping effects on diffusivity and solubility. The results are interpreted using a trapping model. The number of trap sites and their average energies for deuterium in F82H and Batman steels are determined. (orig.)

Influence of traps on the deuterium behaviour in the low activation martensitic steels F82H and Batman

Science.gov (United States)

Serra, E.; Perujo, A.; Benamati, G.

1997-06-01

A time dependent permeation method is used to measure the permeability, diffusivity and solubility of deuterium in the low activation martensitic steels F82H and Batman. The measurements cover the temperature range from 373 to 743 K which includes the onset of deuterium trapping effects on diffusivity and solubility. The results are interpreted using a trapping model. The number of trap sites and their average energies for deuterium in F82H and Batman steels are determined.

Synthesis and evaluation of [[sup 18]F]fluoroprogestins and [[sup 18]F]fluorometoprolol

Energy Technology Data Exchange (ETDEWEB)

De Groot, T J

1993-05-01

The author investigated if specific radioactively labelled compounds could be applied to gain insight into particular psychic diseases, f.e. Parkinson's disease and schizophrenia, by means of Positron Emission Tomography (PET). No appropriate compounds were found. In this thesis the syntheses of fluorine-18 labelled progestins and [beta][sub 1]-adrenergic ligands are described. Three approaches towards [[sup 18]F]fluorination are investigated. The first method concerns direct S[sub N]2-substitution, the second approach is the opening of an epoxide, and the third approach is [[sup 18]F]fluoroalkylation. The positron emitting radionuclide fluorine-18 was used because of its relatively long decay time and the possibility to produce it in high yields and with high specific activity. The target systems which were applied for the production of fluorine-18 are described in chapter two. Important chemical and physical aspects of [[sup 18]F]fluoride are reviewed in the same chapter. In chapter three the synthesis of 21-[[sup 18]F]fluorinated progestins is discussed. The synthesis of four 21-[[sup 18]F]fluoroprogesterone derivatives is described and the results of an in vivo evaluation of two of these ligands are discussed. Possible routes leading to 6[alpha]-[[sup 18]F]fluoroprogestins are presented in chapter four. The radiochemical approaches towards the synthesis of these ligands are discussed. In chapter five the proposed routes to the fluorine-18 labelled [beta][sub 1]-adrenergic ligands are described and evaluated in the synthesis of two model compounds. 1-[[sup 18]F]fluorometoprolol, the [[sup 18]F]fluorinated analogue of a potent beta-blocker, is prepared using one of the investigated methods. The biological effect of fluorine substitution of a [beta][sub 1]-adrenergic ligand is discussed on the basis of an in vitro and in vivo evaluation. 21 figs., 28 schemes, 19 tabs., 182 refs.

Carrier-added and no-carrier-added syntheses of [18F]spiroperidol and [18F]haloperidol

International Nuclear Information System (INIS)

Kilbourn, M.R.; Welch, M.J.; Dence, C.S.; Tewson, T.J.; Saji, H.; Maeda, M.

1984-01-01

Syntheses of [ 18 F]haloperidol and [ 18 F]spiroperidol in both no-carrier-added and carrier-added forms have been accomplished. The no-carrier-added [ 18 F]butyrophenone neuroleptics were prepared in low ( 18 F-neuroleptics were prepared in better (5-17%) yields by 18 F-for- 19 F nucleophilic aromatic substitution. The preparation of all synthetic precursors, and procedures for radiolabeling are fully described. (author)

40K activities and potassium concentrations in tobacco samples of Mexican cigarettes

International Nuclear Information System (INIS)

Martinez, T.; Navarrete, M.; Cabrera, L.; Ramos, A.; Vazquez, K.; Juarez, F.

2007-01-01

Nine brands of tobacco cigarettes manufactured and distributed in the Mexican market were analyzed by γ-spectrometry to certify their nonartificial radioactive contamination. Since natural occurring radioactive materials (NORM) 40 K, 232 Th, 235 U, and 239 U (and decay products from the latter three nuclides) are the main sources for human radiation exposure, the aim of this work was to determine the activity of 40 K and potassium concentration. Averages of 40 K and potassium concentration were of 1.29 ± 0.18 Bq x g -1 , and 4.0 ± 0.57%. The annual dose equivalents to the whole body from ingestion and inhalation of 26 Bq 40 K were 0.23 μSv and 15.8 μSv, respectively. The corresponding 50 years committed dose equivalents was 0.23 μSv. The total committed dose to the lungs due to inhalation of 40 K in tobacco was 16 μSv. Potassium concentrations obtained in this work were in the same range of those obtained by INAA, so showing that the used technique is acute, reproducible, and accessible to laboratories equipped with low background scintillation detectors. (author)

Evaluation of {sup 18}F radioactive concentration in exhaust at cyclotron facility at Chosun University

Energy Technology Data Exchange (ETDEWEB)

Jeong, Cheol Ki; Jang, Han; Lee, Goung Jin [Dept. of Nuclear Engineering, Chsoun University, Gwangju (Korea, Republic of)

2016-11-15

the recent prevalence of PET examinations in Korea has led to an increase in the number of cyclotrons. the medical isotope 18F produced in most cyclotron facilities currently operating in Korea is emitted into the environment during the production of [{sup 18}F]FdG, a cancerdiagnosis reagent. the amount of [{sup 18}F]FdG synthesized determines the radioactive concentration of {sup 18}F in the exhaust. at some facilities, this amount temporarily exceeds the emission limit. In this study, we evaluated the {sup 18}F radioactivity concentration in the exhaust from the cyclotron facility at chosun university. the {sup 18}F radioactivity concentration was measured using an air sampler and a hPGe semiconductor detector. the measurements showed that the radioactive concentration of {sup 18}F in the exhaust at the cyclotron facility at Chosun university was the highest during [{sup 18}F]FdG synthesis but remained under the legal limit of 2,000 Bq m{sup -3}.

Fast and repetitive in-capillary production of [18F]FDG

International Nuclear Information System (INIS)

Wester, Hans-Juergen; Schoultz, Bent Wilhelm; Hultsch, Christina; Henriksen, Gjermund

2009-01-01

The increasing demand for radiopharmaceuticals to be provided reproducibly and flexibly with high frequency for clinical application and animal imaging would be better met by improved or even new strategies for automated tracer production. Radiosynthesis in microfluidic systems, i.e. narrow tubing with a diameter of approximately 50-500 μm, holds promise for providing the means for repetitive multidose and multitracer production. In this study, the performance of a conceptually simple microfluidic device integrated into a fully automated synthesis procedure for in-capillary radiosynthesis (ICR) of clinical grade [ 18 F]FDG was evaluated. The instrumental set-up consisted of pumps for reagent and solvent delivery into small mixing chambers, μ-fluidic capillaries, in-process radioactivity monitoring, solid-phase extraction and on-column deprotection of the 18 F-labelled intermediate followed by on-line formulation of [ 18 F]FDG. In-capillary 18 F-fluorination of 2.1 μmol 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulphonyl-beta-d-mannopyranose (TATM; precursor for [ 18 F]FDG) in acetonitrile (MeCN) at a flow rate of 0.3 ml/min within 40 s and subsequent on-line hydrolysis of the intermediate by treatment with 0.3 M NaOH for 1 min at 40 C resulted in a radiochemical yield of 88 ± 4% within 18 F-fluorination was demonstrated by eight independent, sequentially performed ICRs which provided identical tracer quality (radiochemical purity >97%, MeCN 18 F]FDG with remarkably high efficiency and high yield under fully automated conditions. Although the results concerning the levels of activity need to be confirmed after installation of the equipment in a suitable GMP hot-cell environment, we expect the instrumental design to allow up-scaling without major difficulties or fundamental restrictions. Furthermore, we are convinced that similar or nearly identical procedures, and thus instrumentation, will allow ICR of other 18 F-labelled radiopharmaceuticals. (orig.)

Optimal scanning time window for 18F-FP-(+)-DTBZ (18F-AV-133) summed uptake measurements

International Nuclear Information System (INIS)

Lin, Kun-Ju; Lin, Wey-Yil; Hsieh, Chia-Ju; Weng, Yi-Hsin; Wey, Shiaw-Pyng; Lu, Chin-Song; Skovronsky, Daniel; Yen, Tzu-Chen; Chang, Chee-Jen; Kung, Mei-Ping

2011-01-01

18 F-9-fluoropropyl-(+)-dihydrotetrabenazine ( 18 F-AV-133) is a novel positron emission tomography tracer for imaging the vesicular monoamine transporter II in dopaminergic neuron degeneration, which might be indicative for Parkinson's disease (PD) and other parkinsonism. Studies were performed to optimize the imaging time window for calculating standardized uptake value ratio (SUVR) with correlation to distribution volume ratio (DVR) and in differentiating PD from normal controls (NCs). Methods: Thirteen 18 F-AV-133 positron emission tomography studies were conducted on four NCs (age, 62.3±4.9 years) and nine PD patients (age, 60.8±6.0 years) with Hoehn and Yahr stages 2 to 3. Dynamic images were acquired within 180 min (0–30, 50–140 and 160–180 min) and were rearranged into 14 of 10-min scans. The contralateral striatum was defined as the opposite striatum to the predominantly affected limbs. Volumes of interest (VOIs) of bilateral putamen, caudate nuclei and occipital cortex (OC; as the reference region) were delineated from individual magnetic resonance imaging. SUVRs of striatum to OC were computed from 14 dynamic image sets. The DVRs were computed from Logan graphic analysis by using OC as the input. The performance of SUVR was evaluated based on the correlation of SUVR at each time window to DVR, as well as the Cohen effect size (group mean SUVR difference between PD and NC/standard deviation). Results: 18 F-AV-133 uptake decreased in PD subjects at bilateral striatum especially at contralateral side with posterior putamen predominant as compared with NC. Consistent higher correlations of SUVRs to DVR for all VOIs were observed at later time window and reached to its maximal value of 0.9917 at 90–100 min. The group mean SUVR differences between NC and PD subjects increased and reached relatively stable values after 90 min. The effect sizes for all VOIs were stable across different time window and with the largest value around 90∼120 min

PET imaging of the brain serotonin transporters (SERT) with N,N-dimethyl-2-(2-amino-4-[{sup 18}F]fluorophenylthio)benzylamine (4-[{sup 18}F]-ADAM) in humans: a preliminary study

Energy Technology Data Exchange (ETDEWEB)

Huang, Wen-Sheng [PET Center, Tri-Service General Hospital, Department of Nuclear Medicine, Neihu, Taipei (China); Changhua Christian Hospital, Department of Nuclear Medicine, Changhua (China); Huang, San-Yuan; Ho, Pei-Shen; Yeh, Chin-Bin [Tri-Service General Hospital, Department of Psychiatry, Taipei (China); Ma, Kuo-Hsing [National Defense Medical Center, Department of Biology and Anatomy, Taipei (China); Huang, Ya-Yao; Shiue, Chyng-Yann [PET Center, Tri-Service General Hospital, Department of Nuclear Medicine, Neihu, Taipei (China); PET Center, National Taiwan University Hospital, Department of Nuclear Medicine, Taipei (China); Liu, Ren-Syuan [Taipei Veterans General Hospital, Department of Nuclear Medicine, Taipei (China); Cheng, Cheng-Yi [PET Center, Tri-Service General Hospital, Department of Nuclear Medicine, Neihu, Taipei (China)

2013-01-15

The aim of this study was to assess the feasibility of using 4-[{sup 18}F]-ADAM as a brain SERT imaging agent in humans. Enrolled in the study were 19 healthy Taiwanese subjects (11 men, 8 women; age 33 {+-} 9 years). The PET data were semiquantitatively analyzed and expressed as specific uptake ratios (SUR) and distribution volume ratios (DVR) using the software package PMOD. The SUR and DVR of 4-[{sup 18}F]-ADAM in the raphe nucleus (RN), midbrain (MB), thalamus (TH), striatum (STR) and prefrontal cortex (PFC) were determined using the cerebellum (CB) as the reference region. 4-[{sup 18}F]-ADAM bound to known SERT-rich regions in human brain. The order of the regional brain uptake was MB (RN) > TH > STR > PFC > CB. The DVR (n = 4, t* = 60 min) in the RN, TH, STR and PFC were 3.00 {+-} 0.50, 2.25 {+-} 0.45, 2.05 {+-} 0.31 and 1.40 {+-} 0.13, respectively. The optimal time for imaging brain SERT with 4-[{sup 18}F]-ADAM was 120-140 min after injection. At the optimal imaging time, the SURs (n = 15) in the MB, TH, STR, and PFC were 2.25 {+-} 0.20, 2.28 {+-} 0.20, 2.12 {+-} 0.18 and 1.47 {+-} 0.14, respectively. There were no significant differences in SERT availability between men and women (p < 0.05). The results of this study showed that 4-[{sup 18}F]-ADAM was safe for human studies and its distribution in human brain appeared to correlate well with the known distribution of SERT in the human brain. In addition, it had high specific binding and a reasonable optimal time for imaging brain SERT in humans. Thus, 4-[{sup 18}F]-ADAM may be feasible for assessing the status of brain SERT in humans. (orig.)

Pharmacokinetic Analysis of Dynamic 18F-Fluoromisonidazole PET Data in Non-Small Cell Lung Cancer.

Science.gov (United States)

Schwartz, Jazmin; Grkovski, Milan; Rimner, Andreas; Schöder, Heiko; Zanzonico, Pat B; Carlin, Sean D; Staton, Kevin D; Humm, John L; Nehmeh, Sadek A

2017-06-01

Hypoxic tumors exhibit increased resistance to radiation, chemical, and immune therapies. 18 F-fluoromisonidazole ( 18 F-FMISO) PET is a noninvasive, quantitative imaging technique used to evaluate the magnitude and spatial distribution of tumor hypoxia. In this study, pharmacokinetic analysis (PKA) of 18 F-FMISO dynamic PET extended to 3 h after injection is reported for the first time, to our knowledge, in stage III-IV non-small cell lung cancer (NSCLC) patients. Methods: Sixteen patients diagnosed with NSCLC underwent 2 PET/CT scans (1-3 d apart) before radiation therapy: a 3-min static 18 F-FDG and a dynamic 18 F-FMISO scan lasting 168 ± 15 min. The latter data were acquired in 3 serial PET/CT dynamic imaging sessions, registered with each other and analyzed using pharmacokinetic modeling software. PKA was performed using a 2-tissue, 3-compartment irreversible model, and kinetic parameters were estimated for the volumes of interest determined using coregistered 18 F-FDG images for both the volume of interest-averaged and the voxelwise time-activity curves for each patient's lesions, normal lung, and muscle. Results: We derived average values of 18 F-FMISO kinetic parameters for NSCLC lesions as well as for normal lung and muscle. We also investigated the correlation between the trapping rate ( k 3 ) and delivery rate ( K 1 ), influx rate ( K i ) constants, and tissue-to-blood activity concentration ratios (TBRs) for all tissues. Lesions had trapping rates 1.6 times larger, on average, than those of normal lung and 4.4 times larger than those in muscle. Additionally, for almost all cases, k 3 and K i had a significant strong correlation for all tissue types. The TBR- k 3 correlation was less straightforward, showing a moderate to strong correlation for only 41% of lesions. Finally, K 1 - k 3 voxelwise correlations for tumors were varied, but negative for 76% of lesions, globally exhibiting a weak inverse relationship (average R = -0.23 ± 0.39). However, both

Synthesis and preliminary evaluation of 9-(4-[{sup 18}F]fluoro-3-hydroxymethylbutyl) guanine ([{sup 18}F]FHBG) in HSV1-tk gene transduced hepatoma cell

Energy Technology Data Exchange (ETDEWEB)

Moon, Byung Seok; Lee, Tae Sup [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Myoung Keun [Yonsei University, Wonju (Korea, Republic of)] (and others)

2006-08-15

The HSV1-tk reporter gene system is the most widely used system because of its advantage that direct monitoring is possible without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. In this study, we investigate the usefulness of the reporter probe (substrate), 9-(4-[{sup 18}F]fluoro-3-hydroxymethylbutyl) guanine ([{sup 18}F]FHBG) for non-invasive reporter gene imaging using PET in HSV1-tk expressing hepatoma model. Radiolabeled FHBG was prepared in 8 steps from a commercially available triester. The labeling reaction was carried out by NCA nucleophilic substitution with K[{sup 18}F]/K2.2.2. in acetonitrile using N2-monomethoxytrityl-9-[4-(tosly)-3-monomethoxytritylmethylbutl] guanine as a precursor, followed by deprotection with 1 N HCI. Preliminary biological properties of the probe were evaluated with MCA cells and MCA-tk cells transduced with HSV1-tk reporter gene. In vitro uptake and release-out studies of [{sup 18}F]FHBG were performed, and was analyzed correlation between [{sup 18}F]FHBG uptake ratio according to increasing numeric count of MCA-tk cells and degree of gene expression. MicroPET scan image was obtained with MCA and MCA-tk tumor beating Balb/c-nude mouse model. [{sup 18}F]FHBG was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiochemical yield was about 20-25% (corrected for decay), radiochemical purity was > 95% and specific activity was around > 55.5 GBq/ {mu} mol. Specific accumulation of [{sup 18}F]FHBG was observed in HSV1-tk gene transduced MCA-tk cells but not MCA cells, and consecutive 1 hour release-out results showed more than 86% of uptaked [{sup 18}F]FHBG was retained inside of cells. The uptake of [{sup 18}F]FHBG was showed a highly significant linear correlation (R{sup 2} = 0.995) with increasing percentage of MCA-tk numeric cell count. In microPET scan images, remarkable difference of accumulation was observed for the two type of tumors. [{sup 18}F]FHBG appears

Binding of 18F by cell membranes and cell walls of Streptococcus mutans

International Nuclear Information System (INIS)

Yotis, W.W.; Zeb, M.; McNulty, J.; Kirchner, F.; Reilly, C.; Glendenin, L.

1983-01-01

The binding of 18 F to isolated cell membranes and cell walls of Streptococcus mutans GS-5 or other bacteria was assayed. The attachment of 18 F to these cell envelopes proceeded slowly and reached equilibrium within 60 min. 18 F binding was stimulated by Ca 2+ (1 mM). The binding of 18 F to cellular components was dependent upon the pH, as well as the amount of 18 F and dose of the binder employed. The binding of 18 F by cell walls prepared from fluoride-sensitive and fluoride-resistant cells of S. salivarius and S. mutans did not differ significantly. The pretreatment of cell walls or cell membranes for 60 min at 30 degrees C with 1 mg of RNase, DNase, or trypsin per ml did not influence the binding of 18 F by the walls and membranes of S. mutans GS-5. However, prior exposure of cell membranes to sodium dodecyl sulfate caused a significant reduction in the number of 18 F atoms bound by the membranes. In saturated assay systems, cell membranes of S. mutans GS-5 bound 10(15) to 10(16) atoms of 18 F per mg (dry weight), whereas cell walls from S. mutans GS-5, FA-1, and HS-6 or Actinomyces viscosus T14V and T14AV bound 10(12) to 10(13) atoms of 18 F per mg (dry weight). 18 F in this quantity (10(12) to 10(13) atoms) cannot be detected with the fluoride electrode. The data provide, for the first time, a demonstration of 18 F binding by cell membranes and walls of oral flora

Evaluation of [18F]-ATRi as PET tracer for in vivo imaging of ATR in mouse models of brain cancer

International Nuclear Information System (INIS)

Carlucci, Giuseppe; Carney, Brandon; Sadique, Ahmad; Vansteene, Axel; Tang, Jun; Reiner, Thomas

2017-01-01

Rationale: Ataxia telangiectasia and Rad3-related (ATR) threonine serine kinase is one of the key elements in orchestrating the DNA damage response (DDR). As such, inhibition of ATR can amplify the effects of chemo- and radiation-therapy, and several ATR inhibitors (ATRi) have already undergone clinical testing in cancer. For more accurate patient selection, monitoring and staging, real-time in vivo imaging of ATR could be invaluable; the development of appropriate imaging agents has remained a major challenge. Methods: 3-amino-N-(4-[ 18 F]phenyl)-6-(4-(methylsulfonyl)phenyl) pyrazine-2-carboxamide ([ 18 F]-ATRi), a close analogue of Ve-821, (a clinical ATRi candidate), was readily accomplished similarly to already established synthetic procedures. Structurally, 18 F was introduced at the 4-position of the aromatic ring of Ve-821 for generating a labeled ATR inhibitor. In vitro experiments were conducted in U251 MG glioblastoma cell lines and ex vivo biodistribution were performed in subcutaneous U251 MG xenograft bearing athymic nude mice following microPET imaging. Results: [ 18 F]-ATRi has a similar pharmacokinetic profile to that of Ve-821. Using an U251 MG glioblastoma mouse model, we evaluated the in vivo binding efficiency of [ 18 F]-ATRi. Blood and tumor showed a statistically significant difference between mice injected with only the probe or following blocking experiment with Ve-821 (1.48 ± 0.40%ID/g vs. 0.46 ± 0.12%ID/g in tumor and 1.85 ± 0.47%ID/g vs. 0.84 ± 0.3%ID/g in blood respectively). Conclusions: [ 18 F]-ATRi represents the first 18 F positron emission tomography (PET) ATR imaging agent, and is designed on a low nanomolar and clinically relevant ATR inhibitor.

Design of High Voltage Electrical Breakdown Strength measuring system at 1.8K with a G-M cryocooler

Science.gov (United States)

Li, Jian; Huang, Rongjin; Li, Xu; Xu, Dong; Liu, Huiming; Li, Laifeng

2017-09-01

Impregnating resins as electrical insulation materials for use in ITER magnets and feeder system are required to be radiation stable, good mechanical performance and high voltage electrical breakdown strength. In present ITER project, the breakdown strength need over 30 kV/mm, for future DEMO reactor, it will be greater than this value. In order to develop good property insulation materials to satisfy the requirements of future fusion reactor, high voltage breakdown strength measurement system at low temperature is necessary. In this paper, we will introduce our work on the design of this system. This measuring system has two parts: one is an electrical supply system which provides the high voltage from a high voltage power between two electrodes; the other is a cooling system which consists of a G-M cryocooler, a superfluid chamber and a heat switch. The two stage G-M cryocooler pre-cool down the system to 4K, the superfluid helium pot is used for a container to depress the helium to superfluid helium which cool down the sample to 1.8K and a mechanical heat switch connect or disconnect the cryocooler and the pot. In order to provide the sufficient time for the test, the cooling system is designed to keep the sample at 1.8K for 300 seconds.

Preclinical dynamic 18F-FDG PET - tumor characterization and radiotherapy response assessment by kinetic compartment analysis

International Nuclear Information System (INIS)

Roee, Kathrine; Aleksandersen, Thomas B.; Nilsen, Line B.; Hong Qu; Ree, Anne H.; Malinen, Eirik; Kristian, Alexandr; Seierstad, Therese; Olsen, Dag R.

2010-01-01

Background. Non-invasive visualization of tumor biological and molecular processes of importance to diagnosis and treatment response is likely to be critical in individualized cancer therapy. Since conventional static 18 F-FDG PET with calculation of the semi-quantitative parameter standardized uptake value (SUV) may be subject to many sources of variability, we here present an approach of quantifying the 18 F-FDG uptake by analytic two-tissue compartment modeling, extracting kinetic tumor parameters from dynamic 18 F-FDG PET. Further, we evaluate the potential of such parameters in radiotherapy response assessment. Material and methods. Male, athymic mice with prostate carcinoma xenografts were subjected to dynamic PET either untreated (n=8) or 24 h post-irradiation (7.5 Gy single dose, n=8). After 10 h of fasting, intravenous bolus injections of 10-15 MBq 18 F-FDG were administered and a 1 h dynamic PET scan was performed. 4D emission data were reconstructed using OSEM-MAP, before remote post-processing. Individual arterial input functions were extracted from the image series. Subsequently, tumor 18 F-FDG uptake was fitted voxel-by-voxel to a compartment model, producing kinetic parameter maps. Results. The kinetic model separated the 18 F-FDG uptake into free and bound tracer and quantified three parameters; forward tracer diffusion (k1), backward tracer diffusion (k2), and rate of 18 F-FDG phosphorylation, i.e. the glucose metabolism (k3). The fitted kinetic model gave a goodness of fit (r2) to the observed data ranging from 0.91 to 0.99, and produced parametrical images of all tumors included in the study. Untreated tumors showed homogeneous intra-group median values of all three parameters (k1, k2 and k3), whereas the parameters significantly increased in the tumors irradiated 24 h prior to 18 F-FDG PET. Conclusions. This study demonstrates the feasibility of a two-tissue compartment kinetic analysis of dynamic 18 F-FDG PET images. If validated, extracted

Synthesis of 6-[18F] and 4-[18F]fluoro-L-m-tyrosines via regioselective radiofluorodestannylation

International Nuclear Information System (INIS)

Namavari, Mohammad; Satyamurthy, N.; Phelps, M.E.; Barrio, J.R.; California Univ., Los Angeles, CA

1993-01-01

The regioselective radiofluorodestannylation of 6-trimethylstannyl-L-m-tyrosine derivative with [ 18 F]F 2 and [ 18 F]acetyl hypofluorite afforded, after acid hydrolysis, 6-[ 18 F]fluoro-L-m-tyrosine in radiochemical yields of 23 and 17%, respectively. Similarly, 4-[ 18 F]fluoro-L-m-tyrosine was synthesized in 11% radiochemical yield from the corresponding 4-trimethylstannyl-L-m-tyrosine derivative using [ 18 F]F 2 . The structural analyses of precursors, intermediates, and the final products (after 18 F decay), were carried out by 1 H, 13 C, 19 F, 119 Sn-NMR and high resolution mass spectroscopy. (author)

Automated Synthesis of 18F-Fluoropropoxytryptophan for Amino Acid Transporter System Imaging

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I-Hong Shih

2014-01-01

Full Text Available Objective. This study was to develop a cGMP grade of [18F]fluoropropoxytryptophan (18F-FTP to assess tryptophan transporters using an automated synthesizer. Methods. Tosylpropoxytryptophan (Ts-TP was reacted with K18F/kryptofix complex. After column purification, solvent evaporation, and hydrolysis, the identity and purity of the product were validated by radio-TLC (1M-ammonium acetate : methanol = 4 : 1 and HPLC (C-18 column, methanol : water = 7 : 3 analyses. In vitro cellular uptake of 18F-FTP and 18F-FDG was performed in human prostate cancer cells. PET imaging studies were performed with 18F-FTP and 18F-FDG in prostate and small cell lung tumor-bearing mice (3.7 MBq/mouse, iv. Results. Radio-TLC and HPLC analyses of 18F-FTP showed that the Rf and Rt values were 0.9 and 9 min, respectively. Radiochemical purity was >99%. The radiochemical yield was 37.7% (EOS 90 min, decay corrected. Cellular uptake of 18F-FTP and 18F-FDG showed enhanced uptake as a function of incubation time. PET imaging studies showed that 18F-FTP had less tumor uptake than 18F-FDG in prostate cancer model. However, 18F-FTP had more uptake than 18F-FDG in small cell lung cancer model. Conclusion. 18F-FTP could be synthesized with high radiochemical yield. Assessment of upregulated transporters activity by 18F-FTP may provide potential applications in differential diagnosis and prediction of early treatment response.

Fully automated synthesis system of 3'-deoxy-3'-[18F]fluorothymidine

International Nuclear Information System (INIS)

Oh, Seung Jun; Mosdzianowski, Christoph; Chi, Dae Yoon; Kim, Jung Young; Kang, Se Hun; Ryu, Jin Sook; Yeo, Jeong Seok; Moon, Dae Hyuk

2004-01-01

We developed a new fully automated method for the synthesis of 3'-deoxy-3'-[ 18 F]fluorothymidine ([ 18 F]FLT), by modifying a commercial FDG synthesizer and its disposable fluid pathway. Optimal labeling condition was that 40 mg of precursor in acetonitrile (2 mL) was heated at 150 degree sign C for 100 sec, followed by heating at 85 degree sign C for 450 sec and hydrolysis with 1 N HCl at 105 degree sign C for 300 sec. Using 3.7 GBq of [ 18 F]F - as starting activity, [ 18 F]FLT was obtained with a yield of 50.5±5.2% (n=28, decay corrected) within 60.0±5.4 min including HPLC purification. With 37.0 GBq, we obtained 48.7±5.6% (n=10). The [ 18 F]FLT showed the good stability for 6 h. This new automated synthesis procedure combines high and reproducible yields with the benefits of a disposable cassette system

Imaging Microglial Activation in Untreated First-Episode Psychosis: A PET Study With [18F]FEPPA.

Science.gov (United States)

Hafizi, Sina; Tseng, Huai-Hsuan; Rao, Naren; Selvanathan, Thiviya; Kenk, Miran; Bazinet, Richard P; Suridjan, Ivonne; Wilson, Alan A; Meyer, Jeffrey H; Remington, Gary; Houle, Sylvain; Rusjan, Pablo M; Mizrahi, Romina

2017-02-01

Neuroinflammation and abnormal immune responses are increasingly implicated in the pathophysiology of schizophrenia. Previous positron emission tomography (PET) studies targeting the translocator protein 18 kDa (TSPO) have been limited by high nonspecific binding of the first-generation radioligand, low-resolution scanners, small sample sizes, and psychotic patients being on antipsychotics or not being in the first episode of their illness. The present study uses the novel second-generation TSPO PET radioligand [ 18 F]FEPPA to evaluate whether microglial activation is elevated in the dorsolateral prefrontal cortex and hippocampus of untreated patients with first-episode psychosis. Nineteen untreated patients with first-episode psychosis (14 of them antipsychotic naive) and 20 healthy volunteers underwent a high-resolution [ 18 F]FEPPA PET scan and MRI. Dynamic PET data were analyzed using the validated two-tissue compartment model with arterial plasma input function with total volume of distribution (V T ) as outcome measure. All analyses were corrected for TSPO rs6971 polymorphism (which is implicated in differential binding affinity). No significant differences were observed between patients and healthy volunteers in microglial activation, as indexed by [ 18 F]FEPPA V T , in either the dorsolateral prefrontal cortex or the hippocampus. There were no significant correlations between [ 18 F]FEPPA V T and duration of illness, clinical presentation, or neuropsychological measures after adjusting for multiple testing. The lack of significant differences in [ 18 F]FEPPA V T between groups suggests that microglial activation is not present in first-episode psychosis.

Temperature dependence on shock response of stainless steel

International Nuclear Information System (INIS)

Gu Zhuowei; Jin Xiaogang

1998-01-01

Free surface velocity measurements were reported for HR-2(Cr-Ni-Mn-N) stainless steel, initially heated to 300K∼1000K and shock-compressed to about 8GPa. The corresponding spall strength σ f and Hugoniot elastic limit σ HEL were determined from the wave profiles. It is demonstrated that σ f and σ HEL decrease linearly with increasing temperature T in the range from 300K to 806K, i.e., σ f =5.63-4.32x10 -3 T and σ HEL =2.08-1.54x10 -3 T, and in the range of 806K∼980K, σ HEL increases from 0.84GPa at 806K to 0.93GPa at 980K, σ f has a negligible increase to 2.15GPa from 2.14GPa. Primary TEM test on recovery samples identified the existence of intermatallic compound Ni 3 Ti in the sample of 980K

F-18 Radiopharmaceuticals

International Nuclear Information System (INIS)

2001-12-01

This document includes 8 presentations delivered at the symposium. The topics discussed include: optimization of accelerator production of 18 F- and 18 F 2 -fluorodeoxyglucose; radiopharmaceuticals synthesis, synthesis modules, pharmacopoeia and GLP; quality control; radiation safety of production and application; PET imaging in human medicine. Each presentation has been indexed separately

Evaluation of Prostate Cancer Bone Metastases with 18F-NaF and 18F-Fluorocholine PET/CT.

Science.gov (United States)

Beheshti, Mohsen; Rezaee, Alireza; Geinitz, Hans; Loidl, Wolfgang; Pirich, Christian; Langsteger, Werner

2016-10-01

18 F-fluorocholine is a specific promising agent for imaging tumor cell proliferation, particularly in prostate cancer, using PET/CT. It is a beneficial tool in the early detection of marrow-based metastases because it excludes distant metastases and evaluates the response to hormone therapy. In addition, 18 F-fluorocholine has the potential to differentiate between degenerative and malignant osseous abnormalities because degenerative changes are not choline-avid; however, the agent may accumulate in recent traumatic bony lesions. On the other hand, 18 F-NaF PET/CT can indicate increased bone turnover and is generally used in the assessment of primary and secondary osseous malignancies, the evaluation of response to treatment, and the clarification of abnormalities on other imaging modalities or clinical data. 18 F-NaF PET/CT is a highly sensitive method in the evaluation of bone metastases from prostate cancer, but it has problematic specificity, mainly because of tracer accumulation in degenerative and inflammatory bone diseases. In summary, 18 F-NaF PET/CT is a highly sensitive method, but 18 F-fluorocholine PET/CT can detect early bone marrow metastases and provide greater specificity in the detection of bone metastases in patients with prostate cancer. However, the difference seems not to be significant. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

High-resolution(18)F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging for pituitary adenoma detection in Cushing disease.

Science.gov (United States)

Chittiboina, Prashant; Montgomery, Blake K; Millo, Corina; Herscovitch, Peter; Lonser, Russell R

2015-04-01

OBJECT High-resolution PET (hrPET) performed using a high-resolution research tomograph is reported as having a resolution of 2 mm and could be used to detect corticotroph adenomas through uptake of(18)F-fluorodeoxyglucose ((18)F-FDG). To determine the sensitivity of this imaging modality, the authors compared(18)F-FDG hrPET and MRI detection of pituitary adenomas in Cushing disease (CD). METHODS Consecutive patients with CD who underwent preoperative(18)F-FDG hrPET and MRI (spin echo [SE] and spoiled gradient recalled [SPGR] sequences) were prospectively analyzed. Standardized uptake values (SUVs) were calculated from hrPET and were compared with MRI findings. Imaging findings were correlated to operative and histological findings. RESULTS Ten patients (7 females and 3 males) were included (mean age 30.8 ± 19.3 years; range 11-59 years). MRI revealed a pituitary adenoma in 4 patients (40% of patients) on SE and 7 patients (70%) on SPGR sequences.(18)F-FDG hrPET demonstrated increased(18)F-FDG uptake consistent with an adenoma in 4 patients (40%; adenoma size range 3-14 mm). Maximum SUV was significantly higher for(18)F-FDG hrPET-positive tumors (difference = 5.1, 95% CI 2.1-8.1; p = 0.004) than for(18)F-FDG hrPET-negative tumors.(18)F-FDG hrPET positivity was not associated with tumor volume (p = 0.2) or dural invasion (p = 0.5). Midnight and morning ACTH levels were associated with(18)F-FDG hrPET positivity (p = 0.01 and 0.04, respectively) and correlated with the maximum SUV (R = 0.9; p = 0.001) and average SUV (R = 0.8; p = 0.01). All(18)F-FDG hrPET-positive adenomas had a less than a 180% ACTH increase and(18)F-FDG hrPET-negative adenomas had a greater than 180% ACTH increase after CRH stimulation (p = 0.03). Three adenomas were detected on SPGR MRI sequences that were not detected by(18)F-FDG hrPET imaging. Two adenomas not detected on SE (but no adenomas not detected on SPGR) were detected on(18)F-FDG hrPET. CONCLUSIONS While(18)F-FDG hrPET imaging can

Radiation and chemical stability of 2-deoxy-2-[18F]fluoro-D-glucose radiopharmaceutical. Author-review of thesis

International Nuclear Information System (INIS)

Buriova, M.

2004-07-01

)FDG carrier in 2-[ 18 F]FDG preparation was found to be 6 mg · dm -3 and in combination with a radiometric detector the specific activity 6.6 GBq · μmol -1 of 2-[ 18 F]FDG was found. The main oxidation products of ( 19 F)FDG and glucose by Fenton's reagent were arabonic acid at 14-23% yield, gluconic acid 12%, both glucuronic acid and arabinose at 5%. In case of ( 19 F)FDG among the principal products 2-fluorgluconic acid and 2-fluorgluconic acids by 2.7 % and 4% yields respectively were identified. The dose rates in real solutions of 2-[ 18 F]FDG, as well as the radiation-chemical yields of radioactive (fluorinated), but also further products of autoradiolysis of 2-[ 18 F]FDG radiopharmaceutical were assessed. Dose rate comprises about 140 Gy · h -1 , the annihilation radiation contribution being about 50% of the dose. As the main autoradiolysis products of 3.3 · 10 -5 M solution of 2-[ 18 F]FDG were established: glucose (as additive) - 0.14 mM, arabinose - 2.8 μM (G=0.07/100 eV), gluconic (G=0.05 /100 eV) and glucuronic acids (1.8 - 0.5) μM (G=0.01/100 eV). All 2-[ 19 F]fluorogluconic, 2-[ 19 F]fluorogluconic, arabinose and araburonic acids occurred under 0.5 μM concentration. The LC/MS system combined with a radiometric detector discovered two radioactive products of autoradiolysis of 2-[ 18 F]FDG: 2-[ 18 F]fluorogluconic and 2-[ 18 F]fluoroglucuronic acids, which were established by quantitative calibration. The radiation-chemical yield of glucuronic acid is G=0.004 /100 eV and 2-gluconic acid is about 0.003/100 eV. 2-( 18 F)fluoroglucuronic acid occurrence was about (0.51 ± 0.10 ) % of 2-( 18 F)FDG activity, and 2-( 18 F)fluorogluconic acid (0.30 ± 0.04) %. Activity belonging to free ( 18 F)F- was about (0.20 ± 0.05) %. Radiochemical purity of 2-[ 18 F]FDG radiopharmaceutical after expiration time was established as (99.0 ± 0.2) % what is much higher than that prescribed by pharmacopoeia (> 95 % 2-[ 18 F]FDG). The 1% of radiochemical impurities belonging to

The Semi-automatic Synthesis of 18F-fluoroethyl-choline by Domestic FDG Synthesizer

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ZHOU Ming

2016-02-01

Full Text Available As an important complementary imaging agent for 18F-FDG, 18F-fluoroethyl-choline (18F-FECH has been demonstrated to be promising in brain and prostate cancer imaging. By using domestic PET-FDG-TI-I CPCU synthesizer, 18F-FECH was synthesized by different reagents and consumable supplies. The C18 column was added before the product collection bottle to remove K2.2.2. The 18F-FECH was synthesized by PET-FDG-IT-I synthesizer efficiently about 30 minutes by radiochemical yield of 42.0% (no decay corrected, n=5, and the radiochemical purity was still more than 99.0% after 6 hours. The results showed the domestic PET-FDG-IT-I synthesizer could semi-automatically synthesize injectable 18F-FECH in high efficiency and radiochemical purity

Radiosynthesis and biological evaluation of N-(2-[18F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine as a PET tracer for oncologic imaging.

Science.gov (United States)

Tang, Caihua; Nie, Dahong; Tang, Ganghua; Gao, Siyuan; Liu, Shaoyu; Wen, Fuhua; Tang, Xiaolan

2017-07-01

Several 11 C and 18 F labeled 3,4-dihydroxy-l-phenylalanine (l-DOPA) analogues have been used for neurologic and oncologic diseases, especially for brain tumors and neuroendocrine tumors PET imaging. However, 18 F-labeled N-substituted l-DOPA analogues have not been reported so far. In the current study, radiosynthesis and biological evaluation of a new 18 F-labeled l-DOPA analogue, N-(2-[ 18 F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine ([ 18 F]FPDOPA) for tumor PET imaging are performed. The synthesis of [ 18 F]FPDOPA was via a two-step reaction sequence from 4-nitrophenyl-2-[ 18 F]fluoropropionate ([ 18 F]NFP). The biodistribution of [ 18 F]FPDOPA was determined in normal Kunming mice. In vitro competitive inhibition and protein incorporation experiments were performed with SPC-A-1 lung adenocarcinoma cell lines. PET/CT studies of [ 18 F]FPDOPA were conducted in C6 rat glioma and SPC-A-1 human lung adenocarcinoma and H460 human large cell lung cancer-bearing nude mice. [ 18 F]FPDOPA was prepared with a decay-corrected radiochemical yield of 28±5% and a specific activity of 50±15GBq/μmol (n=10) within 125min. In vitro cell experiments showed that [ 18 F]FPDOPA uptake in SPC-A-1 cells was primarily transported through Na + -independent system L, with Na + -dependent system B 0,+ and system ASC partly involved in it. Biodistribution data in mice showed that renal-bladder route was the main excretory system of [ 18 F]FPDOPA. PET imaging demonstrated intense accumulation of [ 18 F]FPDOPA in several tumor xenografts, with (8.50±0.40)%ID/g in C6 glioma, (6.30±0.12)%ID/g in SPC-A-1 lung adenocarcinoma, and (6.50±0.10)%ID/g in H460 large cell lung cancer, respectively. A novel N-substituted 18 F-labeled L-DOPA analogue [ 18 F]FPDOPA is synthesized and evaluated in vitro and in vivo. The results support that [ 18 F]FPDOPA seems to be a potential PET tracer for tumor imaging, especially be a better potential PET tracer than [ 18 F]fluoro-2-deoxy-d-glucose ([ 18 F

Preclinical characterization of {sup 18}F-D-FPHCys, a new amino acid-based PET tracer

Energy Technology Data Exchange (ETDEWEB)

Denoyer, Delphine; Kirby, Laura [Peter MacCallum Cancer Centre, Molecular Imaging and Targeted Therapeutics Laboratory, East Melbourne, Victoria (Australia); Peter MacCallum Cancer Centre, Translational Research Laboratory, Melbourne, Victoria (Australia); Waldeck, Kelly [Peter MacCallum Cancer Centre, Translational Research Laboratory, Melbourne, Victoria (Australia); Roselt, Peter; Neels, Oliver C. [Peter MacCallum Cancer Centre, Molecular Imaging and Targeted Therapeutics Laboratory, East Melbourne, Victoria (Australia); Bourdier, Thomas [Royal Prince Alfred Hospital, Department PET and Nuclear Medicine, Sydney, New South Wales (Australia); Shepherd, Rachael; Katsifis, Andrew [Australian Nuclear Science and Technology Organisation, ANSTO LifeSciences, Sydney, New South Wales (Australia); Hicks, Rodney J. [Peter MacCallum Cancer Centre, Molecular Imaging and Targeted Therapeutics Laboratory, East Melbourne, Victoria (Australia); Peter MacCallum Cancer Centre, Translational Research Laboratory, Melbourne, Victoria (Australia); University of Melbourne, Department of Medicine, Melbourne, Victoria (Australia)

2012-04-15

The imaging potential of a new {sup 18}F-labelled methionine derivative, S-(3-[{sup 18}F]fluoropropyl)-d-homocysteine ({sup 18}F-D-FPHCys), and its selectivity for amino acid transporter subtypes were investigated in vitro and by imaging of human tumour xenografts. Expression of members of the system L (LAT isoforms 1-4 and 4F2hc) and ASCT (ASCT isoforms 1 and 2) amino acid transporter subclasses were assessed by quantitative real-time PCR in four human tumour models, including A431 squamous cell carcinoma, PC3 prostate cancer, and Colo 205 and HT-29 colorectal cancer lines. The first investigations for the characterization of {sup 18}F-D-FPHCys were in vitro uptake studies by comparing it with [1-{sup 14}C]-l-methionine ({sup 14}C-MET) and in vivo by PET imaging. In addition, the specific involvement of LAT1 transporters in {sup 18}F-D-FPHCys accumulation was tested by silencing LAT1 mRNA transcription with siRNAs. To determine the proliferative activity in tumour xenografts ex vivo, Ki-67 staining was used as a biomarker. A431 cells showed the highest {sup 18}F-D-FPHCys uptake in vitro and in vivo followed by Colo 205, PC3 and HT-29. A similar pattern of retention was observed with {sup 14}C-MET. {sup 18}F-D-FPHCys retention was strongly correlated with LAT1 expression both in vitro (R {sup 2} = 0.85) and in vivo (R{sup 2} = 0.99). Downregulation of LAT1 by siRNA inhibited {sup 18}F-D-FPHCys uptake, demonstrating a clear dependence on this transporter for tumour uptake. Furthermore, {sup 18}F-D-FPHCys accumulation mirrored cellular proliferation. The favourable properties of {sup 18}F-D-FPHCys make this tracer a promising imaging probe for detection of tumours as well as for the noninvasive evaluation and monitoring of tumour growth. (orig.)

Monitoring of anti-cancer treatment with (18)F-FDG and (18)F-FLT PET

DEFF Research Database (Denmark)

Jensen, Mette Munk; Kjaer, Andreas

2015-01-01

treatment effect early in a treatment course and by that to stratify patients into responders and non-responders. With 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine((18)F-FLT) two of the cancer hallmarks, altered energy metabolism and increased cell proliferation, can......Functional imaging of solid tumors with positron emission tomography (PET) imaging is an evolving field with continuous development of new PET tracers and discovery of new applications for already implemented PET tracers. During treatment of cancer patients, a general challenge is to measure...... be visualized and quantified non-invasively by PET. With (18)F-FDG and (18)F-FLT PET changes in energy metabolism and cell proliferation can thereby be determined after initiation of cancer treatment in both clinical and pre-clinical studies in order to predict, at an early time-point, treatment response...

Low carbohydrate diet before 18F-FDG tumor imaging contributes to reduce myocardial 18F-FDG uptake

International Nuclear Information System (INIS)

Miao Weibing; Chen Shaoming; Zheng Shan; Wu Jing; Peng Jiequan; Jiang Zhihong

2014-01-01

Objective: To evaluate whether low carbohydrate diet before 18 F-FDG tumor imaging could reduce myocardial 18 F-FDG uptake. Methods: From April 2011 to January 2012, 70 patients were enrolled in this study.They were randomly divided into control group (34 cases) and test group (36 cases). Patients in control group were on regular diet, while those in test group had low carbohydrate diet in the evening before imaging. Blood samples were taken before injection of 18 F-FDG for the measurement of serum glucose, free fatty acid,insulin and ketone body. Whole body 18 F-FDG tomography was performed with dual-head coincidence SPECT. The myocardial uptake of FDG was assessed visually and scored as 0 for no uptake, 1 for uptake lower than liver, 2 for uptake similar to liver, 3 for uptake higher than liver, and 4 for remarkable uptake.The ratio of myocardium to liver (H/L) was calculated. Two-sample t test, Wilcoxon rank sum test and linear correlation analysis were performed. Results: The myocardial uptake in test group was significantly lower than that in control group with H/L ratios of 0.94±0.57 and 1.50±1.04, respectively (t=-2.75, P<0.05). The concentrations of serum free fatty acid and ketone body in test group were significantly higher than those in control group: (0.671±0.229) mmol/L vs (0.547±0.207) mmol/L and (0.88±0.60) mmol/L vs (0.57±0.32) mmol/L, t=2.38 and 2.67, both P<0.05. The concentrations of glucose and insulin were (5.28±1.06) mmol/L and (35.16±33.70) pmol/L in test group, which showed no significant difference with those in control group ((5.19±0.78) mmol/L and (41.64±35.13) pmol/L, t=0.39 and-0.79, both P>0.05). A negative correlation was found between the myocardial uptake of 18 F-FDG and serum free fatty acid/ketone body concentration (r=-0.40, -0.33, both P<0.01), respectively. There was no correlation between the myocardial uptake of 18 F-FDG and glucose/insulin (r=-0.02, 0.13, both P>0.05), respectively. Conclusion: Low carbohydrate

Radiosynthesis and biological evaluation of 18F-labeled 4-anilinoquinazoline derivative (18F-FEA-Erlotinib) as a potential EGFR PET agent.

Science.gov (United States)

Huang, Shun; Han, Yanjiang; Chen, Min; Hu, Kongzhen; Qi, Yongshuai; Sun, Penghui; Wang, Men; Wu, Hubing; Li, Guiping; Wang, Quanshi; Du, Zhiyun; Zhang, Kun; Zhao, Suqing; Zheng, Xi

2018-04-01

Epidermal growth factor receptor (EGFR) has gained significant attention as a therapeutic target. Several EGFR targeting drugs (Gefitinib and Erlotinib) have been approved by US Food and Drug Administration (FDA) and have received high approval in clinical treatment. Nevertheless, the curative effect of these medicines varied in many solid tumors because of the different levels of expression and mutations of EGFR. Therefore, several PET radiotracers have been developed for the selective treatment of responsive patients who undergo PET/CT imaging for tyrosine kinase inhibitor (TKI) therapy. In this study, a novel fluorine-18 labeled 4-anilinoquinazoline based PET tracer, 1N-(3-(1-(2- 18 F-fluoroethyl)-1H-1,2,3-triazol-4-yl)phenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine ( 18 F-FEA-Erlotinib), was synthesized and biological evaluation was performed in vitro and in vivo. 18 F-FEA-Erlotinib was achieved within 50min with over 88% radiochemical yield (decay corrected RCY), an average specific activity over 50GBq/μmol, and over 99% radiochemical purity. In vitro stability study showed no decomposition of 18 F-FEA-Erlotinib after incubated in PBS and FBS for 2h. Cellular uptake and efflux experiment results indicated the specific binding of 18 F-FEA-Erlotinib to HCC827 cell line with EGFR exon 19 deletions. In vivo, Biodistribution studies revealed that 18 F-FEA-Erlotinib exhibited rapid blood clearance both through hepatobiliary and renal excretion. The tumor uptake of 18 F-FEA-Erlotinib in HepG2, HCC827, and A431 tumor xenografts, with different EGFR expression and mutations, was visualized in PET images. Our results demonstrate the feasibility of using 18 F-FEA-Erlotinib as a PET tracer for screening EGFR TKIs sensitive patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

The use of 18F-Fluoro-deoxy-glucose positron emission tomography (18F-FDG PET as a non-invasive pharmacodynamic biomarker to determine the minimally pharmacologically active dose of AZD8835, a novel PI3Kα inhibitor.

Directory of Open Access Journals (Sweden)

Juliana Maynard

Full Text Available The phosphatidyl inositol 3 kinase (PI3K, AKT and mammalian target of rapamycin (mTOR signal transduction pathway is frequently de-regulated and activated in human cancer and is an important therapeutic target. AZD8835 is a PI3K inhibitor, with selectivity against PI3K α and δ isoforms, which is currently in Phase 1 clinical trials. 18F-Fluoro-deoxy-glucose positron emission tomography (18F-FDG PET is a non-invasive pharmacodynamic imaging biomarker that has become an integral part of drug development. It has been used widely with PI3K inhibitors both clinically and pre-clinically because of the role of the PI3K pathway in glucose metabolism. In this study we investigated the potential of 18F-FDG PET as a non-invasive pharmacodynamic biomarker for AZD8835. We sought to understand if 18F-FDG PET could determine the minimally effective dose of AZD8835 and correlate with other pharmacodynamic biomarkers for validation of its use in clinical development. 18F-FDG PET scans were performed in nude mice in the BT474C breast xenograft model. Mice were fasted prior to imaging and static 18F-FDG PET was performed. Treatment groups received AZD8835 by oral gavage at a dose volume of 10ml/kg. Treatment groups received either 3, 6, 12.5, 25 or 50mg/kg AZD8835. Tumour growth was monitored throughout the study, and at the end of the imaging procedure, tumours were taken and a full pharmacodynamic analysis was performed.Results showed that AZD8835 reduced 18F-FDG uptake at a dose of 12.5, 25 and 50mg/kg with no significant reduction at doses of 3 and 6mg/kg. These results were consistent with other pharmacodynamics biomarkers measured and show 18F-FDG PET as a sensitive biomarker with the ability to determine the minimal effective dose of AZD8835.Our pre-clinical studies support the use of 18F-FDG PET imaging as a sensitive and non- invasive pharmacodynamic biomarker (understanding the role of PI3K signalling in glucose uptake for AZD8835 with a decrease in 18

4-[18F]Fluorophenylpiperazines by Improved Hartwig-Buchwald N-Arylation of 4-[18F]fluoroiodobenzene, Formed via Hypervalent λ3-Iodane Precursors: Application to Build-Up of the Dopamine D4 Ligand [18F]FAUC 316

Directory of Open Access Journals (Sweden)

Fabian Kügler

2014-12-01

Full Text Available Substituted phenylpiperazines are often neuropharmacologically active compounds and in many cases are essential pharmacophores of neuroligands for different receptors such as D2-like dopaminergic, serotoninergic and other receptors. Nucleophilic, no-carrier-added (n.c.a. 18F-labelling of these ligands in an aromatic position is desirable for studying receptors with in vivo molecular imaging. 1-(4-[18F]Fluorophenylpiperazine was synthesized in two reaction steps starting by 18F-labelling of a iodobenzene-iodonium precursor, followed by Pd-catalyzed N-arylation of the intermediate 4-[18F]fluoro-iodobenzene. Different palladium catalysts and solvents were tested with particular attention to the polar solvents dimethylformamide (DMF and dimethylsulfoxide (DMSO. Weak inorganic bases like potassium phosphate or cesium carbonate seem to be essential for the arylation step and lead to conversation rates above 70% in DMF which is comparable to those in typically used toluene. In DMSO even quantitative conversation was observed. Overall radiochemical yields of up to 40% and 60% in DMF and DMSO, respectively, were reached depending on the labelling yield of the first step. The fluorophenylpiperazine obtained was coupled in a third reaction step with 2-formyl-1H-indole-5-carbonitrile to yield the highly selective dopamine D4 ligand [18F]FAUC 316.

The Structure of the Silumin Coat on Alloy Cast Steels

Directory of Open Access Journals (Sweden)

T. Szymczak

2012-04-01

Full Text Available The work presents the analysis results of the structure of the coat obtained by dipping in silumin AlSi5 of two grades of alloy cast steel: GX6CrNiTi18-10 (LH18N9T and GX39Cr13 (LH14. The temperature of the silumin bath was 750±5°C, and the hold-up time of the cast steel element τ = 180 s. The absolute thickness of the coat obtained in the given conditions was g = 104 μm on cast steel GX6CrNiTi18-10 and g = 132 μm on GX39Cr13. The obtained coat consisted of three layers of different phase structure. The first layer from the base “g1`” was constructed of the phase AlFe including Si and alloy additives of the tested cast steel grades: Cr and Ni (GX6CrNiTi18-10 and Cr (GX39Cr13. The second layer “g1``” of intermetallic phases AlFe which also contains Si and Cr crystallizes on it. The last, external layer “g2” of the coat consists of the silumin containing the intermetallic phases AlFeSi which additionally can contain alloy additives of the cast steel. It was shown that there were no carbides on the coat of the tested cast steels which are the component of their microstructure, as it took place in the case of the coat on the high speed steels.

Biological distribution of [18F-FDG] using reactor produced [18F

International Nuclear Information System (INIS)

Sierralta, P.; Massardo, T; Gil, M.C; Gonzalez, P; Chandia, M.; Godoy, N.; Troncoso, F

2002-01-01

The animal model that relates biodistribution of a substance is fundamental prior to using it in human beings. For the evaluation of myocardial viability after a recent MI, the use of reactor produced [ 18 F]-FDG (a radiotracer usually obtained in Cyclotron) is proposed, production of which has never been attempted in our country. Specific Activities founded in the different tissues after injection of this radiotracer in an animal model were compared with those obtained by other authors with cyclotron [ 18 F]-FDG. No statistically significant differences in the critical organs were found. Hence, reactor produced [ 18 F]-FDG is a useful radiopharmaceutical in cardiac cellular metabolism assessment (author)

A simplified one-pot synthesis of 9-[(3-[{sup 18}F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine([{sup 18}F]FHPG) and 9-(4-[{sup 18}F]Fluoro-3-hydroxymethylbutyl)guanine ([{sup 18}F]FHBG) for gene therapy

Energy Technology Data Exchange (ETDEWEB)

Shiue, Grace G.; Shiue, Chyng-Yann E-mail: Shiue@rad.upenn.edu; Lee, Roland L.; MacDonald, Douglas; Hustinx, Roland; Eck, Stephen L.; Alavi, Abass A

2001-10-01

9-[(3-[{sup 18}F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([{sup 18}F]FHPG, 2) has been synthesized by nucleophilic substitution of N{sup 2}-(p-anisyldiphenylmethyl)-9-{l_brace}[1-(p-anisyldiphenylmethoxy)-3 -toluenesulfonyloxy-2-propoxy]methyl{r_brace}guanine (1) with potassium [{sup 18}F]fluoride/Kryptofix 2.2.2 followed by deprotection with 1 N HCl and purification with different methods in variable yields. When both the nucleophilic substitution and deprotection were carried out at 90 deg. C and the product was purified by HPLC (method A), the yield of compound 2 was 5-10% and the synthesis time was 90 min from EOB. However, if both the nucleophilic substitution and deprotection were carried out at 120 deg. C and the product was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2 was synthesized at 90 deg. C and purified by Silica Sep-Pak (method B), the yield increased to 10-15% and the synthesis time was 60 min from EOB. Similarly, 9-(4-[{sup 18}F]fluoro-3-hydroxymethylbutyl)guanine ([{sup 18}F]FHBG, 4) was synthesized with method A and method B in 9% and 10-15% yield, respectively, in a synthesis time of 90 and 60 min, respectively, from EOB. Compound 2 was relatively unstable in acidic medium at 120 deg. C while compound 4 was stable under the same condition. Both compound 2 and compound 4 had low lipid/water partition coefficient (0.126{+-}0.022, n=5 and 0.165{+-}0.023, n=5, respectively). Although it contains non-radioactive ganciclovir ({approx}5-30 {mu}g) as a chemical by-product, compound 2 synthesized by method B has a similar uptake in 9L glioma cells as that synthesized by method A, and is a potential tracer for imaging herpes simplex virus thymidine kinase gene expression in tumors using PET. Similarly, compound 4 synthesized by method B contains {approx}10-25 {mu}g of penciclovir as a chemical by-product. Thus, the simplified one pot synthesis (method B) is a useful method for synthesizing both compound 2 and compound 4 in

Effect of titanium on the creep deformation behaviour of 14Cr-15Ni-Ti stainless steel

Science.gov (United States)

Latha, S.; Mathew, M. D.; Parameswaran, P.; Nandagopal, M.; Mannan, S. L.

2011-02-01

14Cr-15Ni-Ti modified stainless steel alloyed with additions of phosphorus and silicon is a potential candidate material for the future cores of Prototype Fast Breeder Reactor. In order to optimise the titanium content in this steel, creep tests have been conducted on the heats with different titanium contents of 0.18, 0.23, 0.25 and 0.36 wt.% at 973 K at various stress levels. The stress exponents indicated that the rate controlling deformation mechanism was dislocation creep. A peak in the variation of rupture life with titanium content was observed around 0.23 wt.% titanium and the peak was more pronounced at lower stresses. The variation in creep strength with titanium content was correlated with transmission electron microscopic investigations. The peak in creep strength exhibited by the material with 0.23 wt.% titanium is attributed to the higher volume fraction of fine secondary titanium carbide (TiC) precipitates.

Effect of titanium on the creep deformation behaviour of 14Cr-15Ni-Ti stainless steel

Energy Technology Data Exchange (ETDEWEB)

Latha, S. [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam, Tamil Nadu 603 102 (India); Mathew, M.D., E-mail: mathew@igcar.gov.in [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam, Tamil Nadu 603 102 (India); Parameswaran, P.; Nandagopal, M. [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam, Tamil Nadu 603 102 (India); Mannan, S.L. [National Engineering College, Kovilpatti, Tamil Nadu 628 503 (India)

2011-02-28

14Cr-15Ni-Ti modified stainless steel alloyed with additions of phosphorus and silicon is a potential candidate material for the future cores of Prototype Fast Breeder Reactor. In order to optimise the titanium content in this steel, creep tests have been conducted on the heats with different titanium contents of 0.18, 0.23, 0.25 and 0.36 wt.% at 973 K at various stress levels. The stress exponents indicated that the rate controlling deformation mechanism was dislocation creep. A peak in the variation of rupture life with titanium content was observed around 0.23 wt.% titanium and the peak was more pronounced at lower stresses. The variation in creep strength with titanium content was correlated with transmission electron microscopic investigations. The peak in creep strength exhibited by the material with 0.23 wt.% titanium is attributed to the higher volume fraction of fine secondary titanium carbide (TiC) precipitates.

Effect of titanium on the creep deformation behaviour of 14Cr-15Ni-Ti stainless steel

International Nuclear Information System (INIS)

Latha, S.; Mathew, M.D.; Parameswaran, P.; Nandagopal, M.; Mannan, S.L.

2011-01-01

14Cr-15Ni-Ti modified stainless steel alloyed with additions of phosphorus and silicon is a potential candidate material for the future cores of Prototype Fast Breeder Reactor. In order to optimise the titanium content in this steel, creep tests have been conducted on the heats with different titanium contents of 0.18, 0.23, 0.25 and 0.36 wt.% at 973 K at various stress levels. The stress exponents indicated that the rate controlling deformation mechanism was dislocation creep. A peak in the variation of rupture life with titanium content was observed around 0.23 wt.% titanium and the peak was more pronounced at lower stresses. The variation in creep strength with titanium content was correlated with transmission electron microscopic investigations. The peak in creep strength exhibited by the material with 0.23 wt.% titanium is attributed to the higher volume fraction of fine secondary titanium carbide (TiC) precipitates.

Friction stir welding of F/M ODS steel plug and F/M steel tube

Energy Technology Data Exchange (ETDEWEB)

Kang, Suk Hoon, E-mail: shkang77@kaeri.re.kr [Nuclear Materials Division, Korea Atomic Energy Research Institute (Korea, Republic of); Vasudevan, M. [Materials Technology Division, Indira Gandhi Centre for Atomic Research, Kalpakkam (India); Noh, Sanghoon; Jin, Hyun Ju; Jang, Jinsung; Kim, Tae Kyu [Nuclear Materials Division, Korea Atomic Energy Research Institute (Korea, Republic of)

2016-11-01

Highlights: • Friction stir welding (FSW) was used for joining of oxide dispersion strengthened (ODS) steel plug and F/M steel tube. • The curvature and smaller thickness of tube was the major limitation for applying FSW method, it was solved using specially designed jig. • Considerable hardening occurs in the joint because the cooling rate was sufficient to reproduce a martensitic microstructure. • The measured hoop strength of the FSWed joint was 70–90 MPa, the value was at around 70% of the tube. - Abstract: Friction stir welding (FSW) was used for joining of oxide dispersion strengthened (ODS) steel plug and F/M steel tube. The dimensions of the tube included outer diameter of 7 mm, wall thickness of 0.5 mm. The objective was to find suitable process variables for gaining enough frictional heat from those thin and curved pieces. A specially designed jig was used for stabilization and slow rotation of tube during FSW. Additionally, the plug was designed to overlap the tube. Inconel 718 was used as FSW tool, the diameter was 3.5 mm. The adequate rotation speed of the tool and jig were 1200 rpm and 1.5 rpm, respectively. The joining was successfully accomplished using above combination, showing a good possibility. The hoop stress tests of joint were conducted by blowing Ar gas into the tube, the flow rate of gas was 10 MPa/min. The measured hoop stress was 70–90 MPa, the value was at around 70% of the tube.

Friction stir welding of F/M ODS steel plug and F/M steel tube

International Nuclear Information System (INIS)

Kang, Suk Hoon; Vasudevan, M.; Noh, Sanghoon; Jin, Hyun Ju; Jang, Jinsung; Kim, Tae Kyu

2016-01-01

Highlights: • Friction stir welding (FSW) was used for joining of oxide dispersion strengthened (ODS) steel plug and F/M steel tube. • The curvature and smaller thickness of tube was the major limitation for applying FSW method, it was solved using specially designed jig. • Considerable hardening occurs in the joint because the cooling rate was sufficient to reproduce a martensitic microstructure. • The measured hoop strength of the FSWed joint was 70–90 MPa, the value was at around 70% of the tube. - Abstract: Friction stir welding (FSW) was used for joining of oxide dispersion strengthened (ODS) steel plug and F/M steel tube. The dimensions of the tube included outer diameter of 7 mm, wall thickness of 0.5 mm. The objective was to find suitable process variables for gaining enough frictional heat from those thin and curved pieces. A specially designed jig was used for stabilization and slow rotation of tube during FSW. Additionally, the plug was designed to overlap the tube. Inconel 718 was used as FSW tool, the diameter was 3.5 mm. The adequate rotation speed of the tool and jig were 1200 rpm and 1.5 rpm, respectively. The joining was successfully accomplished using above combination, showing a good possibility. The hoop stress tests of joint were conducted by blowing Ar gas into the tube, the flow rate of gas was 10 MPa/min. The measured hoop stress was 70–90 MPa, the value was at around 70% of the tube.

Cosmogenic excess of 40K and the flux of fast neutrons in meteorites

International Nuclear Information System (INIS)

Stegmann, W.; Begemann, F.

1975-01-01

Results are reported of a mass spectrometric investigation of the content and isotopic composition of potassium from the mesosiderite Emery (silicate phase) and the chondrite Elenovka (bulk). Normalized to the Nier value of 39 K/ 41 K = 13.47, the 40 K in Emery (K-content 220 +- 25 ppm) was found to be enriched by (4.03 +- 0.30)%, the potassium from Elenovka (760 +- 50 ppm) to be indistinguishable from terrestrial potassium. Evidence is presented that the excess 40 K in the silicates from Emery (Ca-content 6.06 weight %) has been produced essentially by secondary cosmic ray neutrons via the 40 Ca(n,p)-reaction. The total excess of (2.57 +- 0.39) x 10 14 40 K-atoms/gCa together with the excitation function of the 40 Ca(n,p)-reaction and the neutron flux spectrum of Arnold, Honda and Lal yields a dose of fast neutrons (2 MeV 16 neutrons/cm 2 and an average flux during the cosmic ray exposure age T = (134 +- 12) Myrs of PHI = (17.4 +- 3.1) neutrons/cm 2 sec. (orig./BJ) [de

Definition of multi-state weighted k-out-of-n: F systems

DEFF Research Database (Denmark)

Ding, Yi; Wu, Qiuwei; Zio, Enrico

2012-01-01

of the Multi-state Weighted k-out-of-n: G System- the Multi-state Weighted k-out-of-n: F System has not been clearly defined and discussed. In this short communication, the basic definition of the Multi-state Weighted k-out-of-n: F System model is proposed. The relationship between the Multi-state Weighted k...

Effects of sodium environment on the mechanical properties of Fe-2 1/4Cr-1Mo steel

International Nuclear Information System (INIS)

Chopra, O.K.

Mechanical property data on isothermally annealed, thermally aged, and sodium-exposed Fe-2 1/4Cr-1Mo steel are analyzed to evaluate the influence of the sodium environment as well as the effects of the microstructural and compositional changes that occur in the steel during long-term exposure to sodium. Correlations are developed to predict the environmental effects on tensile, creep, fatigue, and creep-fatigue properties of Fe-2 1/4Cr-1Mo steel in sodium. The results indicate that at temperatures <823 K (550 deg. C), degradation of mechanical properties is essentially due to thermal aging. Loss of carbon from the steel reduces both the tensile and creep-rupture strength, but has little or no effect on the fatigue properties. The cyclic properties of Fe-2 1/4Cr-1Mo steel in sodium are superior to those in air. The creep-fatigue behaviour in sodium is significantly different from that in an air environment. The creep-fatigue data are analyzed using the interactive damage rate equations to predict the time-dependent fatigue bahaviour of isothermally annealed Fe-2 1/4Cr-1Mo steel in sodium. (author)

Localization of ( sup 18 F)fluorodeoxyglucose in mouse brain neurons with micro-autoradiography

Energy Technology Data Exchange (ETDEWEB)

Yamada, Susumu; Kubota, Roko; Kubota, Kazuo [Department of Radiology and Nuclear Medicine, The Research Institute for Tuberculosis and Cancer (Japan); Ishiwata, Kiichi; Ido, Tatsuo [Tohoku Univ., Sendai (Japan). Cyclotron and Radioisotope Center

1990-12-11

This is the first study of micro-autoradiography (micro-ARG) for ({sup 18}F)2-fluoro-2-deoxy-D-glucose (({sup 18}F)FDG). The localization of ({sup 18}F)FDG was demonstrated in dendrites of neuron and also in the myelinated axon in mouse normal brain in vivo. The nucleolus was relatively free of label. The counted silver grain numbers in autoradiogram were linearly correlated to the {sup 18}F radioactivities in the specimen. The micro-ARG using positron emitting {sup 18}F is a very time-saving technique with 4 hours exposure compared with the conventional method using {sup 3}H- or {sup 14}C-labelled tracers. (author).

Comparison of in vivo binding properties of the 18-kDa translocator protein (TSPO) ligands [18F]PBR102 and [18F]PBR111 in a model of excitotoxin-induced neuroinflammation

International Nuclear Information System (INIS)

Callaghan, P.D.; Gregoire, M.C.; Wimberley, C.A.; Rahardjo, G.L.; Berghofer, P.J.; Zahra, D.; Pham, T.Q.; Jackson, T.; Wyatt, N.; Greguric, I.; Howell, N.R.; Loc'h, C.; Bourdier, T.; Mattner, F.; Katsifis, A.; Siegele, R.; Pastuovic, Z.

2015-01-01

The in vivo binding parameters of the novel imidazopyridine TSPO ligand [ 18 F]PBR102 were assessed and compared with those of [ 18 F]PBR111 in a rodent model of neuroinflammation. The validity of the key assumptions of the simplified reference tissue model (SRTM) for estimation of binding potential (BP) was determined, with validation against a two-tissue compartment model (2TC). Acute neuroinflammation was assessed 7 days after unilateral stereotaxic administration of (R,S)-α-amino-3-hydroxy-5-methyl-4-isoxazolopropionique (AMPA) in anaesthetized adult Wistar rats. Anaesthetized rats were implanted with a femoral arterial cannula then injected with a low mass of [ 18 F]PBR102 or [ 18 F]PBR111 and dynamic images were acquired over 60 min using an INVEON PET/CT camera. Another population of rats underwent the same PET protocol after pretreatment with a presaturating mass of the same unlabelled tracer (1 mg/kg) to assess the validity of the reference region for SRTM analysis. Arterial blood was sampled during imaging, allowing pharmacokinetic determination of radiotracer concentrations. Plasma activity concentration-time curves were corrected for unchanged tracer based on metabolic characterization experiments in a separate cohort of Wistar rats. The stability of neuroinflammation in both imaging cohorts was assessed by [ 125 I] CLINDE TSPO quantitative autoradiography, OX42/GFAP immunohistochemistry, Fluoro-Jade C histology, and elemental mapping using microparticle-induced x-ray emission spectroscopy. The BP of each ligand were assessed in the two cohorts of lesioned animals using both SRTM and a 2TC with arterial parent compound concentration, coupled with the results from the presaturation cohort for comparison and validation of the SRTM. The BPs of [ 18 F]PBR102 [ 18 F]PBR111 were equivalent, with improved signal-to-noise ratio and sensitivity compared with [ 11 C]PK11195. The presaturation study showed differences in the volume of distribution between the

An improved radiosynthesis of the muscarinic M2 radiopharmaceutical, [18F]FP-TZTP

International Nuclear Information System (INIS)

Oosten, Erik M. van; Wilson, Alan A.; Stephenson, Karin A.; Mamo, David C.; Pollock, Bruce G.; Mulsant, Benoit H.; Yudin, Andrei K.; Houle, Sylvain; Vasdev, Neil

2009-01-01

The radioligand 3-(4-(3-[ 18 F]fluoropropylthio)-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,5, 6-tetrahydropyridine ([ 18 F]FP-TZTP) is an agonist with specificity towards subtype 2 of muscarinic acetylcholine (M2) receptors. It is currently the only radiotracer available for imaging M2 receptors in human subjects with positron emission tomography. The present study reports on an improved method for the synthesis of [ 18 F]FP-TZTP, automated using a GE TRACERlab TM FX FN radiosynthesis module. A key facet was the use of a new precursor, 3-(4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazol-3-ylthio) propyl 4-methylbenzenesulfonate. The precursor was fluorinated via nucleophilic displacement of the tosyloxy group by potassium cryptand [ 18 F]fluoride (K[ 18 F]/K 222 ) in CH 3 CN at 80 deg. C for 5 min, and purified by HPLC. Formulated [ 18 F]FP-TZTP was prepared in an uncorrected radiochemical yield of 29±4%, with a specific activity of 138±41 GBq/μmol (3732±1109 mCi/μmol) at the end of synthesis (35 min; n=3). This methodology offers higher yields, faster synthesis times, an optimized precursor, and simpler automation than previously reported

Comparison of 18F-fluoro-L-DOPA, 18F-fluoro-deoxyglucose, and 18F-fluorodopamine PET and 123I-MIBG scintigraphy in the localization of pheochromocytoma and paraganglioma.

NARCIS (Netherlands)

Timmers, H.J.L.M.; Chen, C.C.; Carrasquillo, J.A.; Whatley, M.; Ling, A.; Havekes, B.; Eisenhofer, G.; Martiniova, L.; Adams, K.T.; Pacak, K.

2009-01-01

CONTEXT: Besides (123)I-metaiodobenzylguanidine (MIBG), positron emission tomography (PET) agents are available for the localization of paraganglioma (PGL), including (18)F-3,4-dihydroxyphenylalanine (DOPA), (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG), and (18)F-fluorodopamine ((18)F-FDA). OBJECTIVE:

Steel corrosion in tributyl phosphate in the presence of water and ethyl mercaptan

International Nuclear Information System (INIS)

Pischik, L.M.; Tsinman, A.I.

1979-01-01

Studied is the corrosion of steels St3, 15Kh5M, 08Kh13, 10Kh14G14N4T, 08Kh18G8N2T, 10Kh17N13M2T in TBP, in mixtures of TBP with ethyl mercaptan (EM) and two-phase systems TBP-water and TBP-water-EM at 50-150 deg. In pure TBP St3 corrosion rate is low even at 150 deg. In the presence of water St 3 strongly corrodes at above 50 deg temperature in organic and water layers and also in gas phase. The steel-08Kh18G8N2T at 90 deg in acid TBP is passive and its corrosion rate is lower than 0.01 mm/year. In identical conditions the resistance of stainless steels increases together with chromium content but in TBP with acid number 100 and above at 150 deg all tested steels including steel-10Kh17N13M2T are slightly resistant. Thus, even in absence of corrosion active additions of EM the mixture of TBP-water at higher temperature is agressive in relation not only to carbon steel but also to stainless steels

18F-labelling of oligonucleotides using succinimido 4-[18F]fluorobenzoat

International Nuclear Information System (INIS)

Hedberg, Elisabeth; Laangstroem, Bengt

1998-01-01

A general method for the labelling of oligodeoxynucleotide and oligonucleoside phosphorothioates in the 5'-position with the positron-emitting radionuclide 18 F (t 1/2 = 110 min) is described. The label was incorporated by the reaction of succinimido 4 -[ 18 F]fluorobenzoate 4 with oligonucleotides (18- and 20-mers) modified in the 5'-position with a hexylamine linker. Oligodeoxynucleotides 5'-GCT,AAG,CGA,TGC,CTC,CGT-3' (MTCa) and 5'-GAA,CCT,CTG,AGA,GTT,CAT,CT-3' (CROa) were labelled in 20±3 % (MTCa) and 13±3 % (CROa) radiochemical yields (non-isolated, decay-corrected and based on 4). Oligonucleoside phosphorotioates MTCa (S-MTCa) and CROa (S-CROa) were labelled in 9 and 7% isolated radiochemical yield, respectively (decay-corrected and based on 4). Labelled oligonucleotides and phosphorothioate analogues were separated from their unlabelled counterparts using reversed-phase perfusion chromatography. The molecular mass of a labelled oligonucleotide CROa was determined by ESI-MS after a mixed 18 F/ 19 F fluorobenzoate labelling experiment and corresponded with the expected structure. (au)

Tumor aggressiveness and patient outcome in cancer of the pancreas assessed by dynamic 18F-FDG PET/CT.

Science.gov (United States)

Epelbaum, Ron; Frenkel, Alex; Haddad, Riad; Sikorski, Natalia; Strauss, Ludwig G; Israel, Ora; Dimitrakopoulou-Strauss, Antonia

2013-01-01

This study aimed to assess the role of a quantitative dynamic PET model in pancreatic cancer as a potential index of tumor aggressiveness and predictor of survival. Seventy-one patients with (18)F-FDG-avid adenocarcinoma of the pancreas before treatment were recruited, including 27 with localized tumors (11 underwent pancreatectomy, and 16 had localized nonresectable tumors) and 44 with metastatic disease. Dynamic (18)F-FDG PET images were acquired over a 60-min period, followed by a whole-body PET/CT study. Quantitative data measurements were based on a 2-compartment model, and the following variables were calculated: VB (fractional blood volume in target area), K(1) and k(2) (kinetic membrane transport parameters), k(3) and k(4) (intracellular (18)F-FDG phosphorylation and dephosphorylation parameters, respectively), and (18)F-FDG INF (global (18)F-FDG influx). The single significant variable for overall survival (OS) in patients with localized disease was (18)F-FDG INF. Patients with a high (18)F-FDG INF (>0.033 min(-1)) had a median OS of 6 and 5 mo for nonresectable and resected tumors, respectively, versus 15 and 19 mo for a low (18)F-FDG INF in nonresectable and resected tumors, respectively (P measured by dynamic PET in newly diagnosed pancreatic cancer correlated with the aggressiveness of disease. The (18)F-FDG INF was the single most significant variable for OS in patients with localized disease, whether resectable or not.

Molecular imaging of σ receptors: synthesis and evaluation of the potent σ1 selective radioligand [18F]fluspidine

International Nuclear Information System (INIS)

Fischer, Steffen; Hiller, Achim; Deuther-Conrad, Winnie; Scheunemann, Matthias; Steinbach, Joerg; Brust, Peter; Wiese, Christian; Grosse Maestrup, Eva; Schepmann, Dirk; Wuensch, Bernhard

2011-01-01

Neuroimaging of σ 1 receptors in the human brain has been proposed for the investigation of the pathophysiology of neurodegenerative and psychiatric diseases. However, there is a lack of suitable 18 F-labelled PET radioligands for that purpose. The selective σ 1 receptor ligand [ 18 F]fluspidine (1'-benzyl-3-(2-[ 18 F]fluoroethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]) was synthesized by nucleophilic 18 F - substitution of the tosyl precursor. In vitro receptor binding affinity and selectivity were assessed by radioligand competition in tissue homogenate and autoradiographic approaches. In female CD-1 mice, in vivo properties of [ 18 F]fluspidine were evaluated by ex vivo brain section imaging and organ distribution of intravenously administered radiotracer. Target specificity was validated by organ distribution of [ 18 F]fluspidine after treatment with 1 mg/kg i.p. of the σ receptor antagonist haloperidol or the emopamil binding protein (EBP) inhibitor tamoxifen. In vitro metabolic stability and in vivo metabolism were investigated by LC-MS n and radio-HPLC analysis. [ 18 F]Fluspidine was obtained with a radiochemical yield of 35-45%, a radiochemical purity of ≥ 99.6% and a specific activity of 150-350 GBq/μmol (n = 6) within a total synthesis time of 90-120 min. In vitro, fluspidine bound specifically and with high affinity to σ 1 receptors (K i = 0.59 nM). In mice, [ 18 F]fluspidine rapidly accumulated in brain with uptake values of 3.9 and 4.7%ID/g and brain to blood ratios of 7 and 13 at 5 and 30 min after intravenous application of the radiotracer, respectively. By ex vivo autoradiography of brain slices, resemblance between binding site occupancy of [ 18 F]fluspidine and the expression of σ 1 receptors was shown. The radiotracer uptake in the brain as well as in peripheral σ 1 receptor expressing organs was significantly inhibited by haloperidol but not by tamoxifen. Incubation with rat liver microsomes led to a fast biotransformation of

[{sup 18}F]FE-SUPPY and [{sup 18}F]FE-SUPPY:2 - metabolic considerations

Energy Technology Data Exchange (ETDEWEB)

Haeusler, Daniela [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Nics, Lukas [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Nutritional Sciences, Univ. of Vienna, A-1090 Vienna (Austria); Mien, Leonhard-Key [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Ungersboeck, Johanna [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Inorganic Chemistry, Univ. of Vienna, A-1090 Vienna (Austria); Lanzenberger, Rupert R. [Dept. of Psychiatry and Psychotherapy, Medical Univ. of Vienna, A-1090 Vienna (Austria); Shanab, Karem [Dept. of Drug and Natural Product Synthesis, Univ. of Vienna, A-1090 Vienna (Austria); Sindelar, Karoline M. [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Viernstein, Helmut [Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Wagner, Karl-Heinz [Dept. of Nutritional Sciences, Univ. of Vienna, A-1090 Vienna (Austria); Dudczak, Robert; Kletter, Kurt [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Wadsak, Wolfgang [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Inorganic Chemistry, Univ. of Vienna, A-1090 Vienna (Austria); Mitterhauser, Markus [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Hospital Pharmacy of the General Hospital of Vienna, A-1090 Vienna (Austria)], E-mail: markus.mitterhauser@meduniwien.ac.at

2010-05-15

Introduction: Recently, [{sup 18}F]FE-SUPPY and [{sup 18}F]FE-SUPPY:2 were introduced as the first positron emission tomography (PET) tracers for the adenosine A{sub 3} receptor. Thus, aim of the present study was the metabolic characterization of the two adenosine A{sub 3} receptor PET tracers. Methods: In vitro carboxylesterase (CES) experiments were conducted using incubation mixtures containing different concentrations of the two substrates, porcine CES and phosphate-buffered saline. Enzymatic reactions were stopped by adding acetonitrile/methanol (10:1) after various time points and analyzed by a high-performance liquid chromatography (HPLC) standard protocol. In vivo experiments were conducted in male wild-type rats; tracers were injected through a tail vein. Rats were sacrificed after various time points (n=3), and blood and brain samples were collected. Sample cleanup was performed by an HPLC standard protocol. Results: The rate of enzymatic hydrolysis by CES demonstrated Michaelis-Menten constants in a micromolar range (FE-SUPPY, 20.15 {mu}M, and FE-SUPPY:2, 13.11 {mu}M) and limiting velocities of 0.035 and 0.015 {mu}M/min for FE-SUPPY and FE-SUPPY:2, respectively. Degree of metabolism in blood showed the following: 15 min pi 47.7% of [{sup 18}F]FE-SUPPY was intact compared to 33.1% of [{sup 18}F]FE-SUPPY:2; 30 min pi 30.3% intact [{sup 18}F]FE-SUPPY was found compared to 15.6% [{sup 18}F]FE-SUPPY:2. In brain, [{sup 18}F]FE-SUPPY:2 formed an early hydrophilic metabolite, whereas metabolism of [{sup 18}F]FE-SUPPY was not observed before 30 min pi Conclusion: Knowing that metabolism in rats is several times faster than in human, we conclude that [{sup 18}F]FE-SUPPY should be stable for the typical time span of a clinical investigation. As a consequence, from a metabolic point of view, one would tend to decide in favor of [{sup 18}F]FE-SUPPY.

Synthesis and quality control of 18F-β-FP-CIT as a dopamine transporter imaging agent

International Nuclear Information System (INIS)

Tang Ganghua; Tang Xiaolan; Wang Mingfang; Huang Zuhan

2002-01-01

Objective: To develop 18 F-N-3-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophenyl) nortropane ( 18 F-β-FP-CIT) as dopamine transporter imaging agent. Methods: The labelling of 18 F-β-FP-CIT was performed via a two-step synthesis. The 18 F-fluoropropyl bromide was prepared through a nucleophilic substitution by the use of the aminopolyether potassium complex (K/K222) +18 F - as a phase-transfer reagent, and then by N-fluoroalkylation of 2-β-carbomethoxy-3-β-(4-iodophenyl) nortropane (nor-β-CIT) with 18 F-fluoropropyl bromide the 18 F-β-FP-CIT was formed. Contents and analytical methods of quality control for 18 F-β-FP-CIT were investigated and the main quality criteria were achieved through strict control of the determining parameters by standard procedures. Results: The mean overall radiochemical yield from starting 18 F-fluoride was about 8%, the total radiochemical synthesis time was about 90-110 min, and the radiochemical purity was better than 99% by HPLC and TLC. Tests on sterility and apyrogenicity of 18 F-β-FP-CIT obtained by standard procedures were negative, and tests on other main quality criteria met the requirements of the local pharmacopoeia. Conclusion: 18 F-β-FP-CIT injection can be used in the animal and human PET study

Image-derived input function in dynamic human PET/CT: methodology and validation with 11C-acetate and 18F-fluorothioheptadecanoic acid in muscle and 18F-fluorodeoxyglucose in brain

International Nuclear Information System (INIS)

Croteau, Etienne; Lavallee, Eric; Hubert, Laurent; Rousseau, Jacques A.; Lecomte, Roger; Labbe, Sebastien M.; Carpentier, Andre C.; Pifferi, Fabien; Cunnane, Stephen C.; Benard, Francois

2010-01-01

study with 18 F-FDG, the cerebral metabolic rate of glucose (CMRglc) measured using the uncorrected IDIF was consistently overestimated. The CMRglc obtained using blood sampling was 13.1±3.9 mg/100 g per minute and 14.0±5.7 mg/100 g per minute using the corrected IDIF (r 2 =0.90). Correctly obtained, carotid and femoral artery IDIFs can be used as a substitute for AIFs to perform tracer kinetic modelling in skeletal femoral muscles and brain analyses. (orig.)

Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma

International Nuclear Information System (INIS)

Martiniova, Lucia; Cleary, Susannah; Lai, Edwin W.; Kiesewetter, Dale O.; Seidel, Jurgen; Dawson, Linda F.; Phillips, Jacqueline K.; Thomasson, David; Chen Xiaoyuan; Eisenhofer, Graeme; Powers, James F.; Kvetnansky, Richard

2012-01-01

Purpose: To evaluate the usefulness of [ 18 F]-6-fluorodopamine ([ 18 F]-DA) and [ 18 F]-L-6-fluoro-3,4-dihydroxyphenylalanine ([ 18 F]-DOPA) positron emission tomography (PET) in the detection of subcutaneous (s.c.) and metastatic pheochromocytoma in mice; to assess the expression of the norepinephrine transporter (NET) and vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2), all important for [ 18 F]-DA and [ 18 F]-DOPA uptake. Furthermore, to compare tumor detection by micro-computed tomography (microCT) to magnetic resonance imaging (MRI) in individual mouse. Methods: SUV max values were calculated from [ 18 F]-DA and [ 18 F]-DOPA PET, tumor-to-liver ratios (TLR) were obtained and expression of NET, VMAT1 and VMAT2 was evaluated. Results: [ 18 F]-DA detected less metastatic lesions compared to [ 18 F]-DOPA. TLR values for liver metastases were 2.26–2.71 for [ 18 F]-DOPA and 1.83–2.83 for [ 18 F]-DA. A limited uptake of [ 18 F]-DA was found in s.c. tumors (TLR=0.22-0.27) compared to [ 18 F]-DOPA (TLR=1.56-2.24). Overall, NET and VMAT2 were expressed in all organ and s.c. tumors. However, s.c. tumors lacked expression of VMAT1. We confirmed [ 18 F]-DA's high affinity for the NET for its uptake and VMAT1 and VMAT2 for its storage and retention in pheochromocytoma cell vesicles. In contrast, [ 18 F]-DOPA was found to utilize only VMAT2. Conclusion: MRI was superior in the detection of all organ tumors compared to microCT and PET. [ 18 F]-DOPA had overall better sensitivity than [ 18 F]-DA for the detection of metastases. Subcutaneous tumors were localized only with [ 18 F]-DOPA, a finding that may reflect differences in expression of VMAT1 and VMAT2, perhaps similar to some patients with pheochromocytoma where [ 18 F]-DOPA provides better visualization of lesions than [ 18 F]-DA.