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Sample records for 18f fluoride ion

  1. Cyclotron production of [18F]fluoride ion and [18F]fluorine gas and their medical applications

    NASA Astrophysics Data System (ADS)

    VanBrocklin, H. F.; O'Neil, J. P.

    1997-02-01

    One of the newest low energy cyclotrons for the production of positron emitting isotopes has been sited at Lawrence Berkeley National Laboratory. This prototype CTI RDS-111, proton only, 11 MeV, negative ion machine is capable of producing GBq quantities of fluorine-18 for radiopharmaceutical applications. A CTI designed target changing system developed for this cyclotron can hold up to eight small targets. We have tested two small high pressure CTI silver body target designs for the production of [18F]fluoride ion and compared them to the CTI RDS-112 style low pressure target. The high pressure target can produce up to 100% more activity for a given time and beam current with improved saturation yields. A high pressure aluminum RDS-112 gas target has been used to produce [18F]F2. The fluoride ion produced from this machine has been used to label fluorodeoxyglucose to trace glucose metabolism in patients and the fluorine gas has been used to label fluoro-meta-tyrosine to image therapeutic response to gene therapy in Parkinsonian monkeys.

  2. Rapid and Efficient Radiosyntheses of Meta-substituted [18F]Fluoroarenes from [18F]Fluoride Ion and Diaryliodonium Tosylates within a Microreactor

    PubMed Central

    Chun, Joong-Hyun; Lu, Shuiyu; Pike, Victor W.

    2011-01-01

    Effective methods for the introduction of the short-lived positron-emitter fluorine-18 (t1/2 = 109.7 min) at high specific radioactivity into fluoroarenes are valuable for the development of radiotracers for molecular imaging with positron emission tomography. Here we have explored the scope of the radiofluorination of diaryliodonium salts with no-carrier-added [18F]fluoride ion for the preparation of otherwise difficult to access meta-substituted [18F]fluoroarenes. A microfluidic reaction platform was used to establish optimal radiochemical yields. Rapid, high yielding and selective radiofluorinations were achieved in unsymmetrical diaryliodonium tosylates (ArI+Ar’TsO−) in which Ar carried either a meta electron-withdrawing (CN, NO2, CF3) or a meta electron-donating (Me or MeO) group, and in which the partner aryl group (Ar’) was relatively electron-rich, such as Ph, 3-Me-C6H4, 4-MeO-C6H4, 2-thienyl or 5-Me-2-thienyl. The radiofluorination of appropriate diaryliodonium tosylates is therefore a generally useful method for the preparation of simple [18F]m-fluoroarenes ([18F]ArF). PMID:22016665

  3. [18F]fluorination/decarbonylation: new route to aryl [18F]fluorides.

    PubMed

    Chakraborty, P K; Kilbourn, M R

    1991-01-01

    A new route to aryl [18F]fluorides without electron withdrawing ring substituents has been developed. [18F]Fluorobenzaldehydes, prepared from no-carrier-added (NCA) [18F]fluoride using nucleophilic aromatic substitution of fluoro or nitro groups, were decarbonylated using palladium on charcoal (Pd-C). By this approach 2-methoxy-4-nitrobenzaldehyde was converted to NCA 3-[18F]fluorophenol (25-30%, EOB) and 4-fluoro-2-methoxy-5-methylbenzaldehyde to carrier-added (CA) 3-[18F]fluoro-4-methylphenol (30-40%, EOB). Overall synthesis time was about 2 h. Since the 4-fluoro-2-methoxy-5-methylbenzaldehyde was in turn prepared by methylation and regiospecific formylation of 3-fluoro-4-methylphenol, the overall process represents use of a removable activating group for nucleophilic aromatic substitution with [18F]fluoride for preparation of CA and NCA aryl [18F]fluorides.

  4. Fluorine-18 labeling of small molecules: the use of 18F-labeled aryl fluorides derived from no-carrier-added [18F]fluoride as labeling precursors.

    PubMed

    Wuest, F

    2007-01-01

    The favourable long-half life, the ease of production and the low energy of the emitted positron make 18F an ideal radionuclide for PET imaging. Radiochemistry of 18F basically relies on two distinctive types of reactions: nucleophilic and electrophilic reactions. All syntheses of 18F-labeled radiotracers are based on either [18F]fluoride ion or [18F]fluorine gas as simple primary labeling precursors which are obtained directly from the cyclotron. They can be applied either directly to the radiosynthesis or they can be transformed into more complex labeling precursors enabling the multi-step build-up of organic tracer molecules. The topic of this review is a survey on the application of several 18F-labeled aryl fluorides as building blocks derived from no-carrier-added (n.c.a.) [18F] fluoride to build up small monomeric PET radiotracers at high specific radioactivity by multi-step synthesis procedures.

  5. Production of the PET bone agent (18)F-fluoride ion, simultaneously with (18)F-FDG by a single run of the medical cyclotron with minimal radiation exposure- a novel technique.

    PubMed

    Kumar, Rajeev; Sonkawade, Rajendra G; Tripathi, Madhavi; Sharma, Punit; Gupta, Priyanka; Kumar, Praveen; Pandey, Anil K; Bal, Chandrasekhar; Damle, Nishikant Avinash; Bandopadhayaya, Gurupad

    2014-01-01

    Our aim was to establish an easy and convenient procedure for the preparation of fluorine-18-sodium fluoride ((18)F-NaF) for bone positron emission tomography (PET) during routine (18)F-FDG production using the Explora FDG4 radiochemistry module (EFRM) by single run of Cyclotron with negligible radiation exposure. We compared three techniques for (18)F-NaF production during routine PET radiochemistry at our setup. In one method we used synthesis module and in other two methods we did not. In the first and third method, F-18 was directly extracted from the V-vial and in the second method, (18)F-NaF was extracted by post processing from the EFRM. In the first method, F-18 was extracted directly from V-vial manually by opening the V-vial cap. In the second method, Explora FDG-4 Module was used. First, F-18 was transferred from the V-vial. Then, after post processing in EFRM, pure F-18 was obtained in the product vial. In the third method, pure F-18 was obtained in the product vial with the help of a mechanical robotic arm. The above were followed by routine quality control of (18)F-NaF produced by each method. Results of quality control of the (18)F-NaF obtained by all three methods satisfied all parameters prescribed by the United States Pharmacopeia (USP) and the British Pharmacopeia (BP) including biological, physical and chemical specifications. The radiochemical purity was 98.5±1.5% with Rf 0.006. The level of Kryptofix-222 (K222) in (18)F-NaF was within the prescribed limit. Mean pH of (18)F-NaF was 6.0±1.5. The exposure rate around the hot cell was negligible. In conclusion, from the results it was obvious that by our method number three (18)F-NaF was directly obtained from the V-vial using mechanical robotic arms. This method was the most appropriate with minimized radiation exposure to the handling Radiochemist and was also saving time as compared to the other two methods.

  6. 18F-Fluoride and 18F-Fluorodeoxyglucose Positron Emission Tomography After Transient Ischemic Attack or Minor Ischemic Stroke

    PubMed Central

    Jenkins, William S. A.; Irkle, Agnese; Moss, Alastair; Sng, Greg; Forsythe, Rachael O.; Clark, Tim; Roberts, Gemma; Fletcher, Alison; Lucatelli, Christophe; Rudd, James H. F.; Davenport, Anthony P.; Mills, Nicholas L.; Al-Shahi Salman, Rustam; Dennis, Martin; Whiteley, William N.; van Beek, Edwin J. R.; Dweck, Marc R.; Newby, David E.

    2017-01-01

    Background— Combined positron emission tomography (PET) and computed tomography (CT) can assess both anatomy and biology of carotid atherosclerosis. We sought to assess whether 18F-fluoride or 18F-fluorodeoxyglucose can identify culprit and high-risk carotid plaque. Methods and Results— We performed 18F-fluoride and 18F-fluorodeoxyglucose PET/CT in 26 patients after recent transient ischemic attack or minor ischemic stroke: 18 patients with culprit carotid stenosis awaiting carotid endarterectomy and 8 controls without culprit carotid atheroma. We compared standardized uptake values in the clinically adjudicated culprit to the contralateral asymptomatic artery, and assessed the relationship between radiotracer uptake and plaque phenotype or predicted cardiovascular risk (ASSIGN score [Assessing Cardiovascular Risk Using SIGN Guidelines to Assign Preventive Treatment]). We also performed micro PET/CT and histological analysis of excised plaque. On histological and micro PET/CT analysis, 18F-fluoride selectively highlighted microcalcification. Carotid 18F-fluoride uptake was increased in clinically adjudicated culprit plaques compared with asymptomatic contralateral plaques (log10standardized uptake valuemean 0.29±0.10 versus 0.23±0.11, P=0.001) and compared with control patients (log10standardized uptake valuemean 0.29±0.10 versus 0.12±0.11, P=0.001). 18F-Fluoride uptake correlated with high-risk plaque features (remodeling index [r=0.53, P=0.003], plaque burden [r=0.51, P=0.004]), and predicted cardiovascular risk [r=0.65, P=0.002]). Carotid 18F-fluorodeoxyglucose uptake appeared to be increased in 7 of 16 culprit plaques, but no overall differences in uptake were observed in culprit versus contralateral plaques or control patients. However, 18F-fluorodeoxyglucose did correlate with predicted cardiovascular risk (r=0.53, P=0.019), but not with plaque phenotype. Conclusions— 18F-Fluoride PET/CT highlights culprit and phenotypically high-risk carotid plaque

  7. Production and test of {sup 18}F samples in the SNICS ion source

    SciTech Connect

    Rehm, K.E.; Paul, M.; Roberts, A.; Nickels, J.

    1995-08-01

    For experiments with {sup 18}F beams the output of the SNICS ion source for fluorine ions was investigated. {sup 18}F, which is a well-studied PET isotope, is generated at the medical cyclotron of the University of Wisconsin. Aqueous [{sup 18}F] fluoride ions are produced via the {sup 18}O(p,n){sup 18}F reaction using a 30-{mu}A, 11.4-MeV proton beam bombarding a 95% enriched [{sup 18}O] water target. In order to minimize the {sup 18}O component of the {sup 18}F material the [{sup 18}F] fluoride must be separated from the [{sup 18}O] water. For this purpose the aqueous [{sup 18}F] fluoride solution ({approximately} 0.5-1 ml) is removed from the production target and placed in a glassy carbon vessel. The vessel is heated to 115{degrees}C with He bubbling through the solution, evaporating the water while the {sup 18}F adheres to the vessel walls. When dry, the vessel is filled with 1 ml {sup 18}O-depleted 99.98% [{sup 16}O] water which is again evaporated. After this step is repeated once more the vessel is filled with 1.5 ml [{sup 16}O] water and 200-300 mole of natural KF as carrier material.

  8. Clinical utility of (18)F-fluoride PET/CT in benign and malignant bone diseases.

    PubMed

    Li, Yuxin; Schiepers, Christiaan; Lake, Ralph; Dadparvar, Simin; Berenji, Gholam R

    2012-01-01

    (18)F labeled sodium fluoride is a positron-emitting, bone seeking agent with more favorable skeletal kinetics than conventional phosphate and diphosphonate compounds. With the expanding clinical usage of PET/CT, there is renewed interest in using (18)F-fluoride PET/CT for imaging bone diseases. Growing evidence indicates that (18)F fluoride PET/CT offers increased sensitivity, specificity, and diagnostic accuracy in evaluating metastatic bone disease compared to (99m)Tc based bone scintigraphy. National Oncologic PET Registry (NOPR) has expanded coverage for (18)F sodium fluoride PET scans since February 2011 for the evaluation of osseous metastatic disease. In this article, we reviewed the pharmacological characteristics of sodium fluoride, as well as the clinical utility of PET/CT using (18)F-fluoride in both benign and malignant bone disorders.

  9. Magnetic Droplet Microfluidics as a Platform for the Concentration of [18F]Fluoride and Radiosynthesis of Sulfonyl [18F]Fluoride.

    PubMed

    Fiel, Somewhere A; Yang, Hua; Schaffer, Paul; Weng, Samuel; Inkster, James A H; Wong, Michael C K; Li, Paul C H

    2015-06-17

    The radioisotope 18F is often considered the best choice for positron emission tomography (PET) owing to its desirable chemical and radiochemical properties. However, nucleophilic 18F-fluorination of large, water-soluble biomolecules, based on C-F bond formation, has traditionally been difficult. Thus, several aqueous fluorination approaches that offer significant versatility in radiopharmaceutical synthesis with sensitive targeting vectors have been developed. Furthermore, because 18F decays rapidly, production of these 18F-labeled compounds requires an automated process to reduce production time, reduce radiation exposure, and minimize losses due to the transfer of reagents during tracer synthesis. Herein, we report the use of magnetic droplet microfluidics (MDM) as a means to concentrate [18F]fluoride from the cyclotron target solution, followed by the synthesis of an 18F-labeled compound on a microfluidic platform. Using this method, we have demonstrated 18F preconcentration in a small-volume droplet through the use of anion exchanging magnetic particles. By using MDM, the preconcentration step took approximately 5 min, and the [18F]fluoride solution was preconcentrated by 15-fold. After the preconcentration step, an 18F-labeling reaction was performed on the MDM platform using the S-F bond formation in aqueous conditions to produce an arylsulfonyl [18F]fluoride compound which can be used as a prosthetic group to label PET targeting ligands. The high radiochemical purity of 95±1% was comparable to the 96% previously reported using a conventional method. In addition, when MDM was used, the total synthesis time was improved to 15 min with lower reagent volumes (50-60 μL) used.

  10. No-carrier-added (NCA) aryl [{sup 18}F]fluorides via the nucleophilic aromatic substitution of electron rich aromatic rings

    SciTech Connect

    Ding, Yu-Shin; Fowler, J.S.; Wolf, A.P.

    1991-12-31

    A method for synthesizing no-carrier-added (NCA) aryl [{sup 18}F] fluoride substituted aromatic aldehyde compositions bearing an electron donating group is described. The method includes the step of reacting aromatic nitro aldehydes having a suitably protected hydroxyl substituent on an electron rich ring. The reaction is carried out by nucleophilic aromatic substitution with a no-carrier-added (NCA) [{sup 18}F]fluoride ion. The method can be used to synthesize various no-carrier-added aryl [{sup 18}F]fluoride compositions, including 6-[{sup 18}F]fluoro-L-DOPA, 2-[{sup 18}F]fluorotyrosine, 6-[{sup 18}F]fluoronorepinephrine, and 6-[{sup 18}F]fluorodopamine. In those instances when a racemic mixture of enantiomers is produced by the present invention, such as in the synthesis of 6-[{sup 18}F]fluoronorepinephrine, a preferred method also includes resolution of the racemic mixture on a chiral HPLC column. This procedure results in a high yield of enantiomerically pure [{sup 18}F] labeled isomers, for example [-]-6-[{sup 18}F]fluoronorepinephrine and [+]-6-[{sup 18}F]fluoronorepinephrine.

  11. Identifying active vascular microcalcification by 18F-sodium fluoride positron emission tomography

    PubMed Central

    Irkle, Agnese; Vesey, Alex T.; Lewis, David Y.; Skepper, Jeremy N.; Bird, Joseph L. E.; Dweck, Marc R.; Joshi, Francis R.; Gallagher, Ferdia A.; Warburton, Elizabeth A.; Bennett, Martin R.; Brindle, Kevin M.; Newby, David E.; Rudd, James H.; Davenport, Anthony P.

    2015-01-01

    Vascular calcification is a complex biological process that is a hallmark of atherosclerosis. While macrocalcification confers plaque stability, microcalcification is a key feature of high-risk atheroma and is associated with increased morbidity and mortality. Positron emission tomography and X-ray computed tomography (PET/CT) imaging of atherosclerosis using 18F-sodium fluoride (18F-NaF) has the potential to identify pathologically high-risk nascent microcalcification. However, the precise molecular mechanism of 18F-NaF vascular uptake is still unknown. Here we use electron microscopy, autoradiography, histology and preclinical and clinical PET/CT to analyse 18F-NaF binding. We show that 18F-NaF adsorbs to calcified deposits within plaque with high affinity and is selective and specific. 18F-NaF PET/CT imaging can distinguish between areas of macro- and microcalcification. This is the only currently available clinical imaging platform that can non-invasively detect microcalcification in active unstable atherosclerosis. The use of 18F-NaF may foster new approaches to developing treatments for vascular calcification. PMID:26151378

  12. Retention of [(18)F]fluoride on reversed phase HPLC columns.

    PubMed

    Ory, Dieter; Van den Brande, Jeroen; de Groot, Tjibbe; Serdons, Kim; Bex, Marva; Declercq, Lieven; Cleeren, Frederik; Ooms, Maarten; Van Laere, Koen; Verbruggen, Alfons; Bormans, Guy

    2015-01-01

    As [(18)F]fluoride is a starting reagent in the radiosynthesis of most fluorine-18 labeled positron emission tomography (PET) tracers, its chromatographic behavior on reversed phase (RP) HPLC columns is important for the purification performance and accuracy of RP HPLC quality control methods. We have investigated the chromatographic behavior and recovery of [(18)F]fluoride as a function of the type and brand of RP HPLC column, the pH and the composition of the mobile phase. Elution and elution profile of [(18)F]fluoride from six RP-HPLC columns (Waters XBridge C18 3 mm × 100 mm 3.5 μm; Grace Platinum EPS C18 4.6 mm × 100 mm, 3 μm; Waters XTerra C18 4.6 mm × 250 mm, 5 μm; Phenomenex C18 4.6 mm × 150 mm, 5 μm; Hamilton PRP-1 column 4.1 mm × 150 mm, 5 μm; Merck KGaA Chromolith Performance C18 3 mm × 100 mm) eluted with mobile phase composed of phosphate or acetate buffers (pH 2, 3, 4, 5, 7.3 and 9) and acetonitrile or ethanol as organic modifier were characterized. The elution profile was determined by on-line radioactivity measurement in the column eluate and recovery was calculated by comparison of radioactivity eluted with the HPLC column present or absent in the chromatographic flow path. Interestingly, [(18)F]fluoride recovery increased with increasing pH. At pH 3 all packed silica-based columns showed significant retention of fluorine-18, whereas almost no retention was observed on a polymeric PRP-1 column. However at pH 5, [(18)F]fluoride recovery was above 90% for each tested column. In addition, small differences were observed when changing the composition of the mobile phase. We therefore recommend to use a mobile phase with pH > 5 for silica based C18 columns for both quality control and semi-preparative HPLC of fluorine-18 labeled PET radiopharmaceuticals. If required a lower pH can be used in combination with a polymer based HPLC column.

  13. 18F-Labeled Silicon-Based Fluoride Acceptors: Potential Opportunities for Novel Positron Emitting Radiopharmaceuticals

    PubMed Central

    Bernard-Gauthier, Vadim; Wängler, Carmen; Wängler, Bjoern; Schirrmacher, Ralf

    2014-01-01

    Background. Over the recent years, radiopharmaceutical chemistry has experienced a wide variety of innovative pushes towards finding both novel and unconventional radiochemical methods to introduce fluorine-18 into radiotracers for positron emission tomography (PET). These “nonclassical” labeling methodologies based on silicon-, boron-, and aluminium-18F chemistry deviate from commonplace bonding of an [18F]fluorine atom (18F) to either an aliphatic or aromatic carbon atom. One method in particular, the silicon-fluoride-acceptor isotopic exchange (SiFA-IE) approach, invalidates a dogma in radiochemistry that has been widely accepted for many years: the inability to obtain radiopharmaceuticals of high specific activity (SA) via simple IE. Methodology. The most advantageous feature of IE labeling in general is that labeling precursor and labeled radiotracer are chemically identical, eliminating the need to separate the radiotracer from its precursor. SiFA-IE chemistry proceeds in dipolar aprotic solvents at room temperature and below, entirely avoiding the formation of radioactive side products during the IE. Scope of Review. A great plethora of different SiFA species have been reported in the literature ranging from small prosthetic groups and other compounds of low molecular weight to labeled peptides and most recently affibody molecules. Conclusions. The literature over the last years (from 2006 to 2014) shows unambiguously that SiFA-IE and other silicon-based fluoride acceptor strategies relying on 18F− leaving group substitutions have the potential to become a valuable addition to radiochemistry. PMID:25157357

  14. Correlation between thoracic aorta 18F-natrium fluoride uptake and cardiovascular risk

    PubMed Central

    Fiz, Francesco; Morbelli, Silvia; Bauckneht, Matteo; Piccardo, Arnoldo; Ferrarazzo, Giulia; Nieri, Alberto; Artom, Nathan; Cabria, Manlio; Marini, Cecilia; Canepa, Marco; Sambuceti, Gianmario

    2016-01-01

    AIM: To investigating the relationship between thoracic and cardiac 18F-Natrium-Fluoride (18F-NaF) uptake, as a marker of ongoing calcification and cardiovascular risk factors. METHODS: Seventy-eight patients (44 females, mean age 63, range 44-83) underwent whole body 18F-NaF positron emission tomography/computed tomography. Cardiovascular risk (CVR) was used to divide these patients in three categories: Low (LR), medium (MR) and high risk (HR). 18F-NaF uptake was measured by manually drawing volumes of interest on the ascending aorta, on the aortic arch, on the descending aorta and on the myocardium; average standardized uptake value was normalized for blood-pool, to obtain target-to-background ratio (TBR). Values from the three aortic segments were then averaged to obtain an index of the whole thoracic aorta. RESULTS: A significant difference in whole thoracic aorta TBR was detected between HR and LR (1.84 ± 0.76 vs 1.07 ± 0.3, P < 0.001), but also between MR and HR-LR (1.4 ± 0.4, P < 0.02 and P < 0.01, respectively). Significance of this TBR stratification strongly varied among thoracic aorta subsegments and the lowest P values were reached in the descending aorta (P < 0.01). Myocardial uptake provided an effective CVR classes stratification (P < 0.001).Correlation between TBR and CVR was appreciable when the whole thoracic aorta was considered (R = 0.67), but it peaked when correlating the descending thoracic segment (R = 0.75), in comparison with the aortic arch and the ascending segment (R = 0.55 and 0.53, respectively). CONCLUSION: Fluoride uptake within the thoracic aorta wall effectively depicts patients’ risk class and correlates with cardiovascular risk. Descending aorta is the most effective in CVR determination. PMID:26834946

  15. Correlation between mechanical stress by finite element analysis and 18F-fluoride PET uptake in hip osteoarthritis patients.

    PubMed

    Hirata, Yasuhide; Inaba, Yutaka; Kobayashi, Naomi; Ike, Hiroyuki; Yukizawa, Yohei; Fujimaki, Hiroshi; Tezuka, Taro; Tateishi, Ukihide; Inoue, Tomio; Saito, Tomoyuki

    2015-01-01

    18F-fluoride positron emission tomography (18F-fluoride PET) is a functional imaging modality used primarily to detect increased bone metabolism. Increased 18F-fluoride PET uptake suggests an association between increased bone metabolism and load stress at the subchondral level. This study therefore examined the relationship between equivalent stress distribution calculated by finite element analysis and 18F-fluoride PET uptake in patients with hip osteoarthritis. The study examined 34 hips of 17 patients who presented to our clinic with hip pain, and were diagnosed with osteoarthritis or pre-osteoarthritis. The hips with trauma, infection, or bone metastasis of cancer were excluded. Three-dimensional models of each hip were created from computed tomography data to calculate the maximum equivalent stress by finite element analysis, which was compared with the maximum standardized uptake value (SUVmax) examined by 18F-fluoride PET. The SUVmax and equivalent stress were correlated (Spearman's rank correlation coefficient ρ=0.752), and higher equivalent stress values were noted in higher SUVmax patients. The correlation between SUVmax and maximum equivalent stress in osteoarthritic hips suggests the possibility that 18F-fluoride PET detect increased bone metabolism at sites of stress concentration. This study demonstrates the correlation between mechanical stress and bone remodeling acceleration in hip osteoarthritis.

  16. Demons versus Level-Set motion registration for coronary (18)F-sodium fluoride PET.

    PubMed

    Rubeaux, Mathieu; Joshi, Nikhil; Dweck, Marc R; Fletcher, Alison; Motwani, Manish; Thomson, Louise E; Germano, Guido; Dey, Damini; Berman, Daniel S; Newby, David E; Slomka, Piotr J

    2016-02-27

    Ruptured coronary atherosclerotic plaques commonly cause acute myocardial infarction. It has been recently shown that active microcalcification in the coronary arteries, one of the features that characterizes vulnerable plaques at risk of rupture, can be imaged using cardiac gated (18)F-sodium fluoride ((18)F-NaF) PET. We have shown in previous work that a motion correction technique applied to cardiac-gated (18)F-NaF PET images can enhance image quality and improve uptake estimates. In this study, we further investigated the applicability of different algorithms for registration of the coronary artery PET images. In particular, we aimed to compare demons vs. level-set nonlinear registration techniques applied for the correction of cardiac motion in coronary (18)F-NaF PET. To this end, fifteen patients underwent (18)F-NaF PET and prospective coronary CT angiography (CCTA). PET data were reconstructed in 10 ECG gated bins; subsequently these gated bins were registered using demons and level-set methods guided by the extracted coronary arteries from CCTA, to eliminate the effect of cardiac motion on PET images. Noise levels, target-to-background ratios (TBR) and global motion were compared to assess image quality. Compared to the reference standard of using only diastolic PET image (25% of the counts from PET acquisition), cardiac motion registration using either level-set or demons techniques almost halved image noise due to the use of counts from the full PET acquisition and increased TBR difference between (18)F-NaF positive and negative lesions. The demons method produces smoother deformation fields, exhibiting no singularities (which reflects how physically plausible the registration deformation is), as compared to the level-set method, which presents between 4 and 8% of singularities, depending on the coronary artery considered. In conclusion, the demons method produces smoother motion fields as compared to the level-set method, with a motion that is

  17. Demons versus level-set motion registration for coronary 18F-sodium fluoride PET

    NASA Astrophysics Data System (ADS)

    Rubeaux, Mathieu; Joshi, Nikhil; Dweck, Marc R.; Fletcher, Alison; Motwani, Manish; Thomson, Louise E.; Germano, Guido; Dey, Damini; Berman, Daniel S.; Newby, David E.; Slomka, Piotr J.

    2016-03-01

    Ruptured coronary atherosclerotic plaques commonly cause acute myocardial infarction. It has been recently shown that active microcalcification in the coronary arteries, one of the features that characterizes vulnerable plaques at risk of rupture, can be imaged using cardiac gated 18F-sodium fluoride (18F-NaF) PET. We have shown in previous work that a motion correction technique applied to cardiac-gated 18F-NaF PET images can enhance image quality and improve uptake estimates. In this study, we further investigated the applicability of different algorithms for registration of the coronary artery PET images. In particular, we aimed to compare demons vs. level-set nonlinear registration techniques applied for the correction of cardiac motion in coronary 18F-NaF PET. To this end, fifteen patients underwent 18F-NaF PET and prospective coronary CT angiography (CCTA). PET data were reconstructed in 10 ECG gated bins; subsequently these gated bins were registered using demons and level-set methods guided by the extracted coronary arteries from CCTA, to eliminate the effect of cardiac motion on PET images. Noise levels, target-to-background ratios (TBR) and global motion were compared to assess image quality. Compared to the reference standard of using only diastolic PET image (25% of the counts from PET acquisition), cardiac motion registration using either level-set or demons techniques almost halved image noise due to the use of counts from the full PET acquisition and increased TBR difference between 18F-NaF positive and negative lesions. The demons method produces smoother deformation fields, exhibiting no singularities (which reflects how physically plausible the registration deformation is), as compared to the level-set method, which presents between 4 and 8% of singularities, depending on the coronary artery considered. In conclusion, the demons method produces smoother motion fields as compared to the level-set method, with a motion that is physiologically

  18. Demons versus Level-Set motion registration for coronary 18F-sodium fluoride PET

    PubMed Central

    Rubeaux, Mathieu; Joshi, Nikhil; Dweck, Marc R.; Fletcher, Alison; Motwani, Manish; Thomson, Louise E.; Germano, Guido; Dey, Damini; Berman, Daniel S.; Newby, David E.; Slomka, Piotr J.

    2016-01-01

    Ruptured coronary atherosclerotic plaques commonly cause acute myocardial infarction. It has been recently shown that active microcalcification in the coronary arteries, one of the features that characterizes vulnerable plaques at risk of rupture, can be imaged using cardiac gated 18F-sodium fluoride (18F-NaF) PET. We have shown in previous work that a motion correction technique applied to cardiac-gated 18F-NaF PET images can enhance image quality and improve uptake estimates. In this study, we further investigated the applicability of different algorithms for registration of the coronary artery PET images. In particular, we aimed to compare demons vs. level-set nonlinear registration techniques applied for the correction of cardiac motion in coronary 18F-NaF PET. To this end, fifteen patients underwent 18F-NaF PET and prospective coronary CT angiography (CCTA). PET data were reconstructed in 10 ECG gated bins; subsequently these gated bins were registered using demons and level-set methods guided by the extracted coronary arteries from CCTA, to eliminate the effect of cardiac motion on PET images. Noise levels, target-to-background ratios (TBR) and global motion were compared to assess image quality. Compared to the reference standard of using only diastolic PET image (25% of the counts from PET acquisition), cardiac motion registration using either level-set or demons techniques almost halved image noise due to the use of counts from the full PET acquisition and increased TBR difference between 18F-NaF positive and negative lesions. The demons method produces smoother deformation fields, exhibiting no singularities (which reflects how physically plausible the registration deformation is), as compared to the level-set method, which presents between 4 and 8% of singularities, depending on the coronary artery considered. In conclusion, the demons method produces smoother motion fields as compared to the level-set method, with a motion that is physiologically

  19. Optimization and Reproducibility of Aortic Valve 18F-Fluoride Positron Emission Tomography in Patients With Aortic Stenosis

    PubMed Central

    Cartlidge, Timothy R.G.; Jenkins, William S.A.; Adamson, Philip D.; Robson, Phillip; Lucatelli, Christophe; Van Beek, Edwin J.R.; Prendergast, Bernard; Denison, Alan R.; Forsyth, Laura; Rudd, James H.F.; Fayad, Zahi A.; Fletcher, Alison; Tuck, Sharon; Newby, David E.; Dweck, Marc R.

    2016-01-01

    Background— 18F-Fluoride positron emission tomography (PET) and computed tomography (CT) can measure disease activity and progression in aortic stenosis. Our objectives were to optimize the methodology, analysis, and scan–rescan reproducibility of aortic valve 18F-fluoride PET-CT imaging. Methods and Results— Fifteen patients with aortic stenosis underwent repeated 18F-fluoride PET-CT. We compared nongated PET and noncontrast CT, with a modified approach that incorporated contrast CT and ECG-gated PET. We explored a range of image analysis techniques, including estimation of blood-pool activity at differing vascular sites and a most diseased segment approach. Contrast-enhanced ECG-gated PET-CT permitted localization of 18F-fluoride uptake to individual valve leaflets. Uptake was most commonly observed at sites of maximal mechanical stress: the leaflet tips and the commissures. Scan–rescan reproducibility was markedly improved using enhanced analysis techniques leading to a reduction in percentage error from ±63% to ±10% (tissue to background ratio MDS mean of 1.55, bias −0.05, limits of agreement −0·20 to +0·11). Conclusions— Optimized 18F-fluoride PET-CT allows reproducible localization of calcification activity to different regions of the aortic valve leaflet and commonly to areas of increased mechanical stress. This technique holds major promise in improving our understanding of the pathophysiology of aortic stenosis and as a biomarker end point in clinical trials of novel therapies. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02132026. PMID:27733431

  20. Regularized ML reconstruction for time/dose reduction in 18F-fluoride PET/CT studies

    NASA Astrophysics Data System (ADS)

    De Bernardi, Elisabetta; Magnani, Patrizia; Gianolli, Luigi; Carla Gilardi, Maria; Bettinardi, Valentino

    2015-01-01

    We are proposing a regularized reconstruction strategy for the detection of bone lesions in 18F-fluoride whole body PET images obtained with 1 min/bed using the anatomical information provided by co-registered CT images. Bones are recognized on CT images and then transposed into the PET volume framework. During PET reconstruction, two different priors are used for bone and non-bone voxels: the relative difference prior in bone and the P-Gaussian prior in non-bone. After a tuning of the priors’ parameters, the reconstruction strategy has been tested on 6 18F-fluoride PET/CT studies, on a total of 67 lesions. Regularized images provided results comparable to the standard 3 min/bed images, in terms image quality, lesion activity, noise level and noise correlation. The proposed strategy therefore appears to be a useful tool to reduce the acquisition time or the injected dose in 18F-fluoride PET studies.

  1. No-carrier-added (NCA) aryl ([sup 18]F) fluorides via the nucleophilic aromatic substitution of electron rich aromatic rings

    DOEpatents

    Yushin Ding; Fowler, J.S.; Wolf, A.P.

    1993-10-19

    A method for synthesizing no-carrier-added (NCA) aryl [.sup.18 F] fluoride substituted aromatic aldehyde compositions bearing an electron donating group is described. The method of the present invention includes the step of reacting aromatic nitro aldehydes having a suitably protected hydroxyl substitutent on an electron rich ring. The reaction is The U.S. Government has rights in this invention pursuant to Contract Number DE-AC02-76CH00016, between the U.S. Department of Energy and Associated Universities Inc.

  2. Trojan Horse method and radioactive ion beams: study of 18F(p,α)15O reaction at astrophysical energies

    NASA Astrophysics Data System (ADS)

    Gulino, M.; Cherubini, S.; Rapisarda, G. G.; Kubono, S.; Lamia, L.; La Cognata, M.; Yamaguchi, H.; Hayakawa, S.; Wakabayashi, Y.; Iwasa, N.; Kato, S.; Komatsubara, H.; Teranishi, T.; Coc, A.; De Séréville, N.; Hammache, F.; Spitaleri, C.

    2013-03-01

    The Trojan Horse Method was applied for the first time to a Radioactive Ion Beam induced reaction to study the reaction 18F(p,α)15O via the three body reaction 18F(d,α 15O)n at the low energies relevant for astrophysics. The abundance of 18F in Nova explosions is an important issue for the understanding of this astrophysical phenomenon. For this reason it is necessary to study the nuclear reactions that produce or destroy 18F in Novae. 18F(p,α)15O is one of the main 18F destruction channels. Preliminary results are presented in this paper.

  3. Improved 18F Labeling of Peptides with a Fluoride-Aluminum-Chelate Complex

    PubMed Central

    McBride, William J.; D’Souza, Christopher A.; Sharkey, Robert M.; Karacay, Habibe; Rossi, Edmund A.; Chang, Chien-Hsing; Goldenberg, David M.

    2010-01-01

    We reported previously the feasibility to radiolabel peptides with fluorine-18 (18F) using a rapid, one-pot, method that first mixes 18F− with Al3+, and then binds the (Al18F)2+ complex to a NOTA ligand on the peptide. In this report, we examined several new NOTA ligands and determined how temperature, reaction time, and reagent concentration affected the radiolabeling yield. Four structural variations of the NOTA ligand had isolated radiolabeling yields ranging from 5.8% to 87% under similar reaction conditions. All of the Al18F NOTA complexes were stable in vitro in human serum and those that were tested in vivo also were stable. The radiolabeling reactions were performed at 100°C and the peptides could be labeled in as little as five minutes. The IMP467 peptide could be labeled up to 115 GBq/μmol (3100 Ci/mmol), with a total reaction and purification time of 30 min without chromatographic purification. PMID:20540570

  4. Optical reaction cell and light source for [18F] fluoride radiotracer synthesis

    DOEpatents

    Ferrieri, R.A.; Schlyer, D.; Becker, R.J.

    1998-09-15

    An apparatus is disclosed for performing organic synthetic reactions, particularly no-carrier-added nucleophilic radiofluorination reactions for PET radiotracer production. The apparatus includes an optical reaction cell and a source of broadband infrared radiant energy, which permits direct coupling of the emitted radiant energy with the reaction medium to heat the reaction medium. Preferably, the apparatus includes means for focusing the emitted radiant energy into the reaction cell, and the reaction cell itself is preferably configured to reflect transmitted radiant energy back into the reaction medium to further improve the efficiency of the apparatus. The apparatus is well suited to the production of high-yield syntheses of 2-[{sup 18}F]fluoro-2-deoxy-Dglucose. Also provided is a method for performing organic synthetic reactions, including the manufacture of [{sup 18}F]-labeled compounds useful as PET radiotracers, and particularly for the preparation of 2-[{sup 18}F]fluoro-2-deoxy-D-glucose in higher yields than previously possible. 4 figs.

  5. Optical reaction cell and light source for ›18F! fluoride radiotracer synthesis

    DOEpatents

    Ferrieri, Richard A.; Schlyer, David; Becker, Richard J.

    1998-09-15

    Apparatus for performing organic synthetic reactions, particularly no-carrier-added nucleophilic radiofluorination reactions for PET radiotracer production. The apparatus includes an optical reaction cell and a source of broadband infrared radiant energy, which permits direct coupling of the emitted radiant energy with the reaction medium to heat the reaction medium. Preferably, the apparatus includes means for focusing the emitted radiant energy into the reaction cell, and the reaction cell itself is preferably configured to reflect transmitted radiant energy back into the reaction medium to further improve the efficiency of the apparatus. The apparatus is well suited to the production of high-yield syntheses of 2-›.sup.18 F!fluoro-2-deoxy-D-glucose. Also provided is a method for performing organic synthetic reactions, including the manufacture of ›.sup.18 F!-labeled compounds useful as PET radiotracers, and particularly for the preparation of 2-›.sup.18 F!fluoro-2-deoxy-D-glucose in higher yields than previously possible.

  6. Baseline increased 18F-fluoride uptake lesions at vertebral corners on positron emission tomography predict new syndesmophyte development in ankylosing spondylitis: a 2-year longitudinal study.

    PubMed

    Park, Eun-Kyoung; Pak, Kyoungjune; Park, Ji-Heh; Kim, Keunyoung; Kim, Seong-Jang; Kim, In-Joo; Kim, Geun-Tae; Lee, Seung-Geun

    2017-02-02

    The goal of this study was to demonstrate whether increased 18F-fluoride uptake lesions on positron emission tomography (PET) scan can predict new syndesmophyte development in patients with ankylosing spondylitis (AS). In 12 AS patients, 18F-fluoride PET and magnetic resonance imaging (MRI) was performed at baseline, and radiography was performed at baseline and the 2-year follow-up. The following data were recorded: the presence of increased 18F-fluoride uptake lesions on PET defined as an uptake greater than the uptake in the adjacent normal vertebral body; acute (type A) and advanced (type B) corner inflammatory lesions (CILs) and fat lesions on MRI; and syndesmophytes on radiography. Of 231 anterior vertebral corners without syndesmophyte at baseline, 13 type A CILs (5.5%), 2 type B CILs (0.9%), and 20 fat lesions (8.7%) on MRI and six increased fluoride uptake lesions (2.6%) on PET were observed. At the 2-year follow-up, 16 new syndesmophytes (6.9%) in eight AS patients (66.7%) occurred. New syndesmophytes developed significantly more frequently in anterior vertebral corners with increased 18F-fluoride uptake lesions (50%) or fat lesions (25%) at baseline than in those without such lesions (5.8 and 5.2%; p = 0.005 and p = 0.007, respectively). After adjusting confounding factors, baseline increased 18F-fluoride uptake lesions was independently associated with new syndesmophytes development (OR 13.8, 95% CI 1.5-124.3, p = 0.019). Fat lesions were also associated with new syndesmophytes formation. Our data suggest that 18F-fluoride PET may be applied to identify AS patients with high risk of future syndesmophyte formation.

  7. The Role of 18F-Sodium Fluoride PET/CT Bone Scans in the Diagnosis of Metastatic Bone Disease from Breast and Prostate Cancer.

    PubMed

    Kulshrestha, Randeep Kumar; Vinjamuri, Sobhan; England, Andrew; Nightingale, Julie; Hogg, Peter

    2016-12-01

    We describe the role of (18)F-sodium fluoride ((18)F-NaF) PET/CT bone scanning in the staging of breast and prostate cancer. (18)F-NaF PET was initially utilized as a bone scanning agent in the 1960s and early 1970s, however, its use was restricted by the then-available γ-cameras. The advent of hybrid PET/CT cameras in the late 1990s has shown a resurgence of interest in its use and role. After a brief introduction, this paper describes the radiopharmaceutical properties, dosimetry, pharmacokinetics, and mechanism of uptake of (18)F-NaF. The performance of (18)F-NaF PET/CT is then compared with that of conventional bone scintigraphy using current evidence from the literature. Strengths and weaknesses of (18)F-NaF PET/CT imaging are highlighted. Clinical examples of improved accuracy of diagnosis and impact on patient management are illustrated. Limitations of (18)F-NaF PET/CT imaging are outlined.

  8. Double-grid [ 18O]water target for high yield of [ 18F]fluoride production on KIRMAS-13

    NASA Astrophysics Data System (ADS)

    Hong, Bong Hwan; An, Dong Hyun; Chai, Jong Seo; Chang, Hong Suk; Hur, Min Goo; Jung, In Su; Kim, Sangwook; Kim, Yu Seok; Yang, Tae Keun

    2005-12-01

    [18O]water targets were constructed to install on the 13 MeV KIRAMS-13 medical cyclotron for high yield of [18F]fluoride production from enriched [18O]water. Central cavity in titanium body contain [18O]water. Shape of cavity has two different geometries along incident direction of beam. Front volume has a cylinder shape and rear cavity has a fan shape with larger volume to gather ascent vapor bubbles and increase heat transfer area. Total volume of cavity is 1.6 ml. Both open sides of cavity are block with 50 μm titanium foils. Two aluminum grids are placed out side of each foil. Front water-cooled type gird is directly place in the vacuum beam line. Grids were adapted to cool foils and prevent their thermal expansion under high pressure. The target yield is 50 mCi/μA h under 12.5 MeV incident proton beam.

  9. (18)F-sodium fluoride PET/CT for the in vivo visualization of Mönckeberg's sclerosis in a diabetic patient.

    PubMed

    Quirce, R; Martínez-Rodríguez, I; Banzo, I; de Arcocha-Torres, M; Jiménez-Bonilla, J F; Martínez-Amador, N; Ibáñez-Bravo, S; Ramos, L; Amado, J A; Carril, J M

    2015-01-01

    Diabetes is a major frequent cause of atherosclerosis vascular disease. Arterial calcification in diabetic patients is responsible for peripheral vascular involvement. Molecular imaging using (18)F-sodium fluoride ((18)F-NaF) positron emission tomography (PET)/computed tomography (CT) has been recently proposed as a marker to study the in vivo mineralization process in the atheroma plaque. A 69-year-old man with a history of type 2 diabetes and no clinical evidence of peripheral arterial disease underwent an (18)F-NaF PET/CT scan. A linear, well-defined (18)F-NaF uptake was detected along the femoral arteries. In addition, the CT component of the PET/CT identified an unsuspected "tram-track" calcification in his femoral arteries, suggestive of medial calcification (Mönckeberg's sclerosis). In other vascular territories, focal (18)F-NaF uptake was also detected in carotid and aorta atheroma plaques. Molecular imaging with (18)F-NaF PET/CT might provide new functional information about the in vivo vascular calcification process in diabetic patients.

  10. Evolving Role of Molecular Imaging with (18)F-Sodium Fluoride PET as a Biomarker for Calcium Metabolism.

    PubMed

    Raynor, William; Houshmand, Sina; Gholami, Saeid; Emamzadehfard, Sahra; Rajapakse, Chamith S; Blomberg, Björn Alexander; Werner, Thomas J; Høilund-Carlsen, Poul F; Baker, Joshua F; Alavi, Abass

    2016-08-01

    (18)F-sodium fluoride (NaF) as an imaging tracer portrays calcium metabolic activity either in the osseous structures or in soft tissue. Currently, clinical use of NaF-PET is confined to detecting metastasis to the bone, but this approach reveals indirect evidence for disease activity and will have limited use in the future in favor of more direct approaches that visualize cancer cells in the read marrow where they reside. This has proven to be the case with FDG-PET imaging in most cancers. However, a variety of studies support the application of NaF-PET to assess benign osseous diseases. In particular, bone turnover can be measured from NaF uptake to diagnose osteoporosis. Several studies have evaluated the efficacy of bisphosphonates and their lasting effects as treatment for osteoporosis using bone turnover measured by NaF-PET. Additionally, NaF uptake in vessels tracks calcification in the plaques at the molecular level, which is relevant to coronary artery disease. Also, NaF-PET imaging of diseased joints is able to project disease progression in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. Further studies suggest potential use of NaF-PET in domains such as back pain, osteosarcoma, stress-related fracture, and bisphosphonate-induced osteonecrosis of the jaw. The critical role of NaF-PET in disease detection and characterization of many musculoskeletal disorders has been clearly demonstrated in the literature, and these methods will become more widespread in the future. The data from PET imaging are quantitative in nature, and as such, it adds a major dimension to assessing disease activity.

  11. First results of Trojan horse method using radioactive ion beams: 18F(p,α) at astrophysical energies

    NASA Astrophysics Data System (ADS)

    Cherubini, S.; Gulino, M.; Spitaleri, C.; La Cognata, M.; Lamia, L.; Puglia, S.; Rapisarda, G.; Romano, S.; Kubono, S.; Yamaguchi, H.; Binh, D.; Hayakawa, S.; Kurihara, Y.; Wakabayashi, Y.; Bishop, S.; Coc, A.; De Séréville, N.; Hammache, F.

    2014-05-01

    The abundance of 18F in Nova explosions is considered to be an important piece of information for the understanding of this astrophysical phenomenon. It is then necessary to study the nuclear processess that both produce and destroy this isotope in Novae. Among these latter reactions, the 18F(p,α)15O is one of the most important 18F destruction channels. Here we report on an experiment performed using the CRIB apparatus of the Center for Nuclear Study of the University of Tokyo. This was the first experiment that used the Trojan Horse method applied to a Radioactive Ion Beam induced reaction.

  12. First results of Trojan horse method using radioactive ion beams: {sup 18}F(p,α) at astrophysical energies

    SciTech Connect

    Cherubini, S.; Spitaleri, C.; Puglia, S.; Rapisarda, G.; Romano, S.; Gulino, M.; La Cognata, M.; Lamia, L.; Kubono, S.; Wakabayashi, Y.; Yamaguchi, H.; Hayakawa, S.; Kurihara, Y.; Binh, D.; Bishop, S.; Coc, A.; De Séréville, N.; Hammache, F.

    2014-05-02

    The abundance of {sup 18}F in Nova explosions is considered to be an important piece of information for the understanding of this astrophysical phenomenon. It is then necessary to study the nuclear processess that both produce and destroy this isotope in Novae. Among these latter reactions, the {sup 18}F(p,α){sup 15}O is one of the most important {sup 18}F destruction channels. Here we report on an experiment performed using the CRIB apparatus of the Center for Nuclear Study of the University of Tokyo. This was the first experiment that used the Trojan Horse method applied to a Radioactive Ion Beam induced reaction.

  13. Niobium sputtered Havar foils for the high-power production of reactive [18F]fluoride by proton irradiation of [18O]H2O targets.

    PubMed

    Wilson, J S; Avila-Rodriguez, M A; Johnson, R R; Zyuzin, A; McQuarrie, S A

    2008-05-01

    Niobium sputtered Havar entrance foils were used for the production of reactive [(18)F]fluoride by proton irradiation of [(18)O]H(2)O targets under pressurized conditions. The synthesis yield in the routine production of 2-[(18)F]fluoro-2-deoxy-glucose (FDG) was used as an indicative parameter of the reactivity of (18)F. The yield of FDG obtained with (18)F produced in a target with Havar foil was used as a baseline. No statistically significant difference was found in the saturated yields of (18)F when using Havar or Havar-Nb sputtered entrance foils. However, the amount of long-lived radionuclidic impurities decreased more than 10-fold using the Havar-Nb entrance foil. The average decay corrected synthesis yield of FDG, evaluated over a period of more than 2 years, was found to be approximately 5% higher when using a Havar-Nb entrance foil and a marked improvement on the FDG yield consistency was noted. In addition, the frequency of target rebuilding was greatly diminished when using the Nb sputtered entrance foil.

  14. Calcified peritoneal metastasis identified on 18F-fluoride positron emission tomography/computed tomography: Importance of extraosseous uptake of F-18 fluoride.

    PubMed

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

    2016-01-01

    F-18 NaF positron emission tomography/computed tomography (PET/CT) is used for the evaluation of malignant and nonmalignant osseous disease. Extraosseous uptake of 18 fluoride-NaF has been observed in the arterial vasculature, gastrointestinal tract, and genitourinary tract. We describe a case of a woman with carcinoma of unknown primary in whom F-18 NaF PET/CT showed tracer uptake in the calcified peritoneal metastasis. Extraosseous findings on F-18 NaF PET/CT, though rare, may be visualized and may result in important management changes.

  15. Do Fluoride Ions Protect Teeth?

    ERIC Educational Resources Information Center

    Parkin, Christopher

    1998-01-01

    Begins with the procedure and results from an investigation on the effect of fluoride on the reaction between eggshell (substitute teeth) and dilute ethanoic acid. Describes an elegantly modified and improvised apparatus. (DDR)

  16. Differences in regional bone perfusion and turnover between lumbar spine and distal humerus: (18)F-fluoride PET study of treatment-naïve and treated postmenopausal women.

    PubMed

    Frost, Michelle L; Blake, Glen M; Cook, Gary J R; Marsden, Paul K; Fogelman, Ignac

    2009-11-01

    The functional imaging technique of (18)F-fluoride positron emission tomography ((18)F-PET) allows the non-invasive assessment of regional bone blood perfusion and turnover. Bone perfusion and turnover measured using (18)F-PET correlate closely with those obtained experimentally and so they can be readily applied in clinical research studies. The aim of this study was to compare bone perfusion and turnover between the lumbar spine and humerus in both treatment naïve postmenopausal women (n=11) and those on stable antiresorptive therapy (n=12). All women had a BMD T-score of less than -2 at the spine and/or hip. Each woman had a dynamic PET scan of the lumbar spine and distal humerus after injection of 90 MBq (18)F-fluoride. Using a three-compartmental model bone perfusion (K(1)), the net plasma clearance of tracer to bone mineral (K(i)) reflecting regional bone turnover and the rate constants k(2)-k(4) describing the transport of fluoride between plasma, an extravascular bone compartment and bone mineral compartment were calculated. Mean bone perfusion (K(1)) and bone turnover (K(i)) were significantly higher at the lumbar spine compared to the humerus for both treatment-naïve and antiresorptive groups. K(1) values were on average 3 times greater while K(i) was approximately 50% greater at the lumbar spine. The rate constant k(2), the reverse transport of fluoride from the extravascular compartment to plasma, was significantly lower at the humerus compared to the lumbar spine in both groups. The ratio K(i)/K(1) describing the unidirectional extraction efficiency to bone mineral was significantly greater at the humerus compared to the lumbar spine for both study groups. No significant differences between skeletal sites were observed for k(3) or k(4). In conclusion a significant skeletal heterogeneity was observed in terms of bone perfusion and turnover between the lumbar spine and humerus. (18)F-PET may aid in our understanding of the importance of bone perfusion

  17. Synthesis of [18F]fallypride in a micro-reactor

    PubMed Central

    Lu, Shuiyu; Giamis, Anthony M.; Pike, Victor W.

    2008-01-01

    A commercial coiled-tube micro-reactor (NanoTek; Advion) was used as a convenient platform for the synthesis of [18F]fallypride in small doses (0.5–1.5 mCi) for micro-PET studies of brain dopamine subtype-2 receptors in rodents. Each radiosynthesis used low amounts (20–40 μg; 39–77 nmol) of tosylate precursor and [18F]fluoride ion (0.5–2.5 mCi). Optimization of the labeling reaction in the apparatus, with respect to the effects of precursor amount, reaction temperature, flow rate and [18F]fluoride ion to precursor ratio, was achieved rapidly and the decay-corrected radiochemical yield of [18F]fallypride (up to 88%) was reproducible. The low amounts of material used in each radiosynthesis allowed crude [18F]fallypride to be purified rapidly on an analytical-size reverse phase HPLC column, preceding formulation for intravenous injection. Scale-up of the reaction was easily achieved by continuously infusing reagent precursor solutions to obtain [18F]fallypride in much greater quantity. PMID:20047004

  18. Some electronic and magnetic properties of Fluoride ion in Fluoride structure nanocrystals

    NASA Astrophysics Data System (ADS)

    Imtani, Ali Nasir

    2012-01-01

    We have investigated the effects of the environment potential around Fluoride ion on some important electronic and magnetic properties such as dipole polarisability, moment of oscillator strengths S(k) and magnetic susceptibility. The theoretical procedure is based on the variational-perturbation theory with two parameter trial functions incorporated in an ionic model. We estimate these properties in four cases for Fluoride ion; free ion, ion under different potentials, ion in the crystals and ion in nanocrystal, CdF2, CaF2, PbF2, SrF2 and BaF2. Our results indicate that these properties vary with ion environments and the free state of Fluoride ion has higher values and there is linearity behaviour of these properties with lattice constant. For Fluoride ion in nanocrystal, we have found that there is an extra parameter that can also affect the dipole polarisability, the number of ions in the structure.

  19. Transport of 3-fluoro-L-α-methyl-tyrosine (FAMT) by organic ion transporters explains renal background in [(18)F]FAMT positron emission tomography.

    PubMed

    Wei, Ling; Tominaga, Hideyuki; Ohgaki, Ryuichi; Wiriyasermkul, Pattama; Hagiwara, Kohei; Okuda, Suguru; Kaira, Kyoichi; Kato, Yukio; Oriuchi, Noboru; Nagamori, Shushi; Kanai, Yoshikatsu

    2016-02-01

    A PET tracer for tumor imaging, 3-(18)F-l-α-methyl-tyrosine ([(18)F]FAMT), has advantages of high cancer-specificity and low physiological background. In clinical studies, FAMT-PET has been proved useful for the detection of malignant tumors and their differentiation from inflammation and benign lesions. The tumor specific uptake of FAMT is due to its high-selectivity to cancer-type amino acid transporter LAT1 among amino acid transporters. In [(18)F]FAMT PET, kidney is the only organ that shows high physiological background. To reveal transporters involved in renal accumulation of FAMT, we have examined [(14)C]FAMT uptake on the organic ion transporters responsible for the uptake into tubular epithelial cells. We have found that OAT1, OAT10 and OCTN2 transport [(14)C]FAMT. The [(14)C]FAMT uptake was inhibited by probenecid, furosemide and ethacrynic acid, consistent with the properties of the transporters. The amino acid uptake inhibitor, 2-amino-2-norbornanecarboxylic acid (BCH), also inhibited the [(14)C]FAMT uptake, whereas OCTN2-mediated [(14)C]FAMT uptake was Na(+)-dependent. We propose that FAMT uptake by OAT1, OAT10 and OCTN2 into tubular epithelial cells could contribute to the renal accumulation of FAMT. The results from this study would provide clues to the treatments to reduce renal background and enhance tumor uptake as well as to designing PET tracers with less renal accumulation.

  20. Fluoride ion encapsulation by Mg[superscript 2+] ions and phosphates in a fluoride riboswitch

    SciTech Connect

    Ren, Aiming; Rajashankar, Kanagalaghatta R.; Patel, Dinshaw J.

    2012-06-26

    Significant advances in our understanding of RNA architecture, folding and recognition have emerged from structure-function studies on riboswitches, non-coding RNAs whose sensing domains bind small ligands and whose adjacent expression platforms contain RNA elements involved in the control of gene regulation. We now report on the ligand-bound structure of the Thermotoga petrophila fluoride riboswitch, which adopts a higher-order RNA architecture stabilized by pseudoknot and long-range reversed Watson-Crick and Hoogsteen A {sm_bullet} U pair formation. The bound fluoride ion is encapsulated within the junctional architecture, anchored in place through direct coordination to three Mg{sup 2+} ions, which in turn are octahedrally coordinated to water molecules and five inwardly pointing backbone phosphates. Our structure of the fluoride riboswitch in the bound state shows how RNA can form a binding pocket selective for fluoride, while discriminating against larger halide ions. The T. petrophila fluoride riboswitch probably functions in gene regulation through a transcription termination mechanism.

  1. Fluoride ion encapsulation by Mg2+ ions and phosphates in a fluoride riboswitch.

    PubMed

    Ren, Aiming; Rajashankar, Kanagalaghatta R; Patel, Dinshaw J

    2012-05-13

    Significant advances in our understanding of RNA architecture, folding and recognition have emerged from structure-function studies on riboswitches, non-coding RNAs whose sensing domains bind small ligands and whose adjacent expression platforms contain RNA elements involved in the control of gene regulation. We now report on the ligand-bound structure of the Thermotoga petrophila fluoride riboswitch, which adopts a higher-order RNA architecture stabilized by pseudoknot and long-range reversed Watson-Crick and Hoogsteen A•U pair formation. The bound fluoride ion is encapsulated within the junctional architecture, anchored in place through direct coordination to three Mg(2+) ions, which in turn are octahedrally coordinated to water molecules and five inwardly pointing backbone phosphates. Our structure of the fluoride riboswitch in the bound state shows how RNA can form a binding pocket selective for fluoride, while discriminating against larger halide ions. The T. petrophila fluoride riboswitch probably functions in gene regulation through a transcription termination mechanism.

  2. 18F-Sodium Fluoride PET-CT Hybrid Imaging of the Lumbar Facet Joints: Tracer Uptake and Degree of Correlation to CT-graded Arthropathy

    PubMed Central

    Mabray, Marc C.; Brus-Ramer, Marcel; Behr, Spencer C.; Pampaloni, Miguel H.; Majumdar, Sharmila; Dillon, William P.; Talbott, Jason F.

    2016-01-01

    We aim to evaluate 18F-NaF uptake by facet joints with hybrid PET-CT technique. Specifically, we evaluate NaF uptake in the facet joints of the lower lumbar spine, and correlate with the morphologic grade of facet arthropathy on CT. 30 consecutive patients who underwent standard vertex to toes NaF PET-CT for re-staging of primary neoplastic disease without measurable or documented bony metastases were identified. Maximum (SUVmax) and average (SUVavg) standardized uptake values were calculated for each L3-4, L4-5, and L5-S1 facet joint (n = 180) and normalized to average uptake in the non-diseased femur. A Pathria grade (0-3) was assigned to each facet based upon the CT morphology. Spearman's rank correlation was performed for normalized SUVmax and SUVavg with Pathria grade. ANOVA was performed with Tukey-Kramer pairwise tests to evaluate differences in uptake between Pathria groups. Facet normalized SUVmax (r = 0.31, P < 0.001) and SUVavg (r = 0.28, P < 0.001) demonstrated a mild positive correlation with CT Pathria grade. There was a wide range of uptake values within each Pathria grade subgroup with statistically significant differences in uptake only between Pathria grade 3 as compared to grades 0, 1, and 2. In conclusion, NaF uptake and morphologic changes of the facet joint on CT are weakly correlated. Physiologic information provided by NaF uptake is often discrepant with structural findings on CT suggesting NaF PET may supplement conventional structural imaging for identification of pain generating facet joints. Prospective investigation into the relationship of facet joint NaF uptake with pain and response to pain interventions is warranted. PMID:27134557

  3. Aromatic radiofluorination with (/sup 18/F)fluorine gas: 6-(/sup 18/F)fluoro-L-dopa

    SciTech Connect

    Firnau, G.; Chirakal, R.; Garnett, E.S.

    1984-11-01

    A new synthesis is described for the routine production of 3,4-dihydroxy-6-(/sup 18/F)fluoro-phenyl-L-alanine (6-(/sup 18/F)fluoro-L-dopa). The reaction between (/sup 18/F)fluorine gas and 3,4-dihydroxyphenyl-L-alanine (L-dopa) in liquid hydrogen fluoride gave 2-, 5-, and 6-(/sup 18/F)fluoro-L-dopa. 6-(/sup 18/F)Fluoro-L-dopa was isolated by reverse-phase high-pressure liquid chromatography. From 100 mCi (/sup 18/F)F/sub 2/, the method produces 3 mCi of 6-(/sup 18/F)fluoro-L-dopa at the end of synthesis.

  4. Enhanced copper-mediated (18)F-fluorination of aryl boronic esters provides eight radiotracers for PET applications.

    PubMed

    Preshlock, Sean; Calderwood, Samuel; Verhoog, Stefan; Tredwell, Matthew; Huiban, Mickael; Hienzsch, Antje; Gruber, Stefan; Wilson, Thomas C; Taylor, Nicholas J; Cailly, Thomas; Schedler, Michael; Collier, Thomas Lee; Passchier, Jan; Smits, René; Mollitor, Jan; Hoepping, Alexander; Mueller, Marco; Genicot, Christophe; Mercier, Joël; Gouverneur, Véronique

    2016-06-28

    [(18)F]FMTEB, [(18)F]FPEB, [(18)F]flumazenil, [(18)F]DAA1106, [(18)F]MFBG, [(18)F]FDOPA, [(18)F]FMT and [(18)F]FDA are prepared from the corresponding arylboronic esters and [(18)F]KF/K222 in the presence of Cu(OTf)2py4. The method was successfully applied using three radiosynthetic platforms, and up to 26 GBq of non-carrier added starting activity of (18)F-fluoride.

  5. Measurement of the astrophysical S-factor for the {sup 18}F(p,{alpha}) reaction at E = 662 keV/u with a {sup 18}F radioactive beam

    SciTech Connect

    Rehm, K.E.; Blumenthal, D.J.; Gehring, J.

    1995-08-01

    {sup 18}F is produced in stars during the so-called breakout from the hot CNO cycle and is important as one of the links connecting the HCNO cycle with the rp-process by producing {sup 19}Ne via the {sup 18}F(p,{gamma}) reaction. There is, however, a competing reaction {sup 18}F(p,{alpha}){sup 15}O which leads back into the CNO cycle. The importance of {sup 18}F for producing {sup 19}Ne therefore depends strongly on the (p,{gamma}) to (p,{alpha}) cross sections ratio. We have begun to study the {sup 18}F(p,{alpha}){sup 15}O reaction using a {sup 18}F beam. {sup 18}F, which is a well-studied PET isotope, is generated at the medical cyclotron of the University of Wisconsin. Aqueous [{sup 18}F] fluoride ions are produced via the {sup 18}O(p,n){sup 18}F reaction using a 30-{mu}A, 11.4-MeV proton beam bombarding a 95% enriched [{sup 18}O] water target and electroplated onto the end of a 3-mm diameter Al anode. After electroplating, the anodized Al is pressed into a copper cathode insert for the National Electrostatics Corporation SNICS ion source, transported to Argonne National Laboratory and installed in the ion source of the Tandem accelerator at ATLAS. With an activity at the end of the electroplating process of 530 mCi, the starting activity after 2 h, which is the time needed to transport and install the material in the SNICS source, was 250 mCi, corresponding to a total number of {sup 18}F atoms of 8.8 x 10{sup 13}.

  6. Synthesis of high specific activity (+)- and (-)-6-( sup 18 F)fluoronorepinephrine via the nucleophilic aromatic substitution reaction

    SciTech Connect

    Ding, Y.S.; Fowler, J.S.; Gatley, S.J.; Dewey, S.L.; Wolf, A.P. )

    1991-02-01

    The first example of a no-carrier-added {sup 18}F-labeled catecholamine, 6-({sup 18}F)fluoronorepinephrine (6-({sup 18}F)FNE), has been synthesized via nucleophilic aromatic substitution. The racemic mixture was resolved on a chiral HPLC column to obtain pure samples of (-)-6-({sup 18}F)FNE and (+)6-({sup 18}F)FNE. Radiochemical yields of 20% at the end of bombardment (EOB) for the racemic mixture (synthesis time 93 min), 6% for each enantiomer (synthesis time 128 min) with a specific activity of 2-5 Ci/mumol at EOB were obtained. Chiral HPLC peak assignment for the resolved enantiomers was achieved by using two independent methods: polarimetric determination and reaction with dopamine beta-hydroxylase. Positron emission tomography (PET) studies with racemic 6-({sup 18}F)FNE show high uptake and retention in the baboon heart. This work demonstrates that nucleophilic aromatic substitution by ({sup 18}F)fluoride ion is applicable to systems having electron-rich aromatic rings, leading to high specific activity radiopharmaceuticals. Furthermore, the suitably protected dihydroxynitrobenzaldehyde 1 may serve as a useful synthetic precursor for the radiosynthesis of other complex {sup 18}F-labeled radiotracers.

  7. No-carrier-added nucleophilic 18F-labelling in an electrochemical cell exemplified by the routine production of [18F]altanserin.

    PubMed

    Hamacher, K; Coenen, H H

    2006-09-01

    A new type of electrochemical cell with anodic deposition of no-carrier-added [(18)F]fluoride and variable reaction volume has been developed. The reactor is designed for small reaction volumes and non-thermal drying of [(18)F]fluoride. The implementation of this reactor into a complete remotely controlled synthesis device is described for the routine production of [(18)F]altanserin. A radiochemical yield of 23+/-5% was obtained via cryptate-mediated nucleophilic (18)F-fluorination. Batches of up to 6 GBq [(18)F]altanserin, suitable for human application, with a molar activity of >500 GBq/micromol were obtained within 75 min.

  8. Novel fluorogenic probe for fluoride ion based on the fluoride-induced cleavage of tert-butyldimethylsilyl ether

    NASA Astrophysics Data System (ADS)

    Yang, Xiao-Feng

    2007-06-01

    A highly sensitive and selective fluorogenic probe for fluoride ion, 4-methylumbelliferyl tert-butyldimethylsilyl ether (4-MUTBS), was designed and synthesized. 4-MUTBS was a weakly fluorescent compound and was synthesized via the one-step reaction of 4-MU with tert-butyldimethylsilyl chloride. Upon incubation with fluoride ion in acetone-water solution (7:3, v/v), the Si-O bond of 4-MUTBS was cleaved and highly fluorescent 4-methylumbelliferone (4-MU) was released, hence leading to the fluorescence increase of the reaction solution. The fluorescence increase is linearly with fluoride concentration in the range 50-8000 nmol l -1 with a detection limit of 19 nmol l -1 (3 σ). Because of the high affinity of silicon toward fluoride ion, the proposed probe shows excellent selectivity toward fluoride ion over other anions. The method has been successfully applied to the fluoride determination in toothpaste and tap water samples.

  9. Method for selective recovery of PET-usable quantities of [.sup.18 F] fluoride and [.sup.13 N] nitrate/nitrite from a single irradiation of low-enriched [.sup.18 O] water

    DOEpatents

    Ferrieri, Richard A.; Schlyer, David J.; Shea, Colleen

    1995-06-13

    A process for simultaneously producing PET-usable quantities of [.sup.13 N]NH.sub.3 and [.sup.18 F]F.sup.- for radiotracer synthesis is disclosed. The process includes producing [.sup.13 N]NO.sub.2.sup.- /NO.sub.3.sup.- and [.sup.18 F]F.sup.- simultaneously by exposing a low-enriched (20%-30%) [.sup.18 O]H.sub.2 O target to proton irradiation, sequentially isolating the [.sup.13 N]NO.sub.2.sup.- /NO.sub.3.sup.- and [.sup.18 F]F.sup.- from the [.sup.18 O]H.sub.2 O target, and reducing the [.sup.13 N]NO.sub.2.sup.- /NO.sub.3.sup.- to [.sup.13 N]NH.sub.3. The [.sup.13 N]NH.sub.3 and [.sup.18 F]F.sup.- products are then conveyed to a laboratory for radiotracer applications. The process employs an anion exchange resin for isolation of the isotopes from the [.sup.18 O]H.sub.2 O, and sequential elution of [.sup.13 N]NO.sub.2.sup.- /NO.sub.3.sup.- and [ .sup.18 F]F.sup.- fractions. Also the apparatus is disclosed for simultaneously producing PET-usable quantities of [.sup.13 N]NH.sub.3 and [.sup.18 F]F.sup.- from a single irradiation of a single low-enriched [.sup.18 O]H.sub.2 O target.

  10. Method for selective recovery of PET-usable quantities of [{sup 18}F] fluoride and [{sup 13}N] nitrate/nitrite from a single irradiation of low-enriched [{sup 18}O] water

    DOEpatents

    Ferrieri, R.A.; Schlyer, D.J.; Shea, C.

    1995-06-13

    A process for simultaneously producing PET-usable quantities of [{sup 13}N]NH{sub 3} and [{sup 18}F]F{sup {minus}} for radiotracer synthesis is disclosed. The process includes producing [{sup 13}N]NO{sub 2}{sup {minus}}/NO{sub 3}{sup {minus}}and [{sup 18}F]F{sup {minus}} simultaneously by exposing a low-enriched (20%-30%) [{sup 18}O]H{sub 2}O target to proton irradiation, sequentially isolating the [{sup 13}N]NO{sub 2}{sup {minus}}/NO{sub 3}{sup {minus}} and [{sup 18}F]F{sup {minus}} from the [{sup 18}O]H{sub 2}O target, and reducing the [{sup 13}N]NO{sub 2}{sup {minus}}/NO{sub 3}{sup {minus}} to [{sup 13}N]NH{sub 3}. The [{sup 13}N]NH{sub 3} and [{sup 18}F]F{sup {minus}} products are then conveyed to a laboratory for radiotracer applications. The process employs an anion exchange resin for isolation of the isotopes from the [{sup 18}O]H{sub 2}O, and sequential elution of [{sup 13}N]NO{sub 2}{sup {minus}}/NO{sub 3}{sup {minus}} and [{sup 18}F]F{sup {minus}} fractions. Also the apparatus is disclosed for simultaneously producing PET-usable quantities of [{sup 13}N]NH{sub 3} and [{sup 18}F]F{sup {minus}} from a single irradiation of a single low-enriched [{sup 18}O]H{sub 2}O target. 2 figs.

  11. Sources of carrier F-19 in F-18 fluoride

    SciTech Connect

    Link, J. M.; Shoner, S. C.; Krohn, K. A.

    2012-12-19

    Fluorine-18 is used for many PET radiopharmaceuticals. Theoretically {sup 18}F should be carrier free and a good candidate for nanochemistry. However, {sup 18}F has 10 to 1000 times more stable fluorine atoms than radioactive atoms. In order to understand the source of carrier fluoride and other ions associated with {sup 18}F radiosynthesis, anion concentrations of different components of {sup 18}F target systems as well as solvents and chemicals used in radiosynthesis were measured. Results: The enriched water used for production of {sup 18}F had low levels of anions. In general, the sources of anions, particularly of fluoride, were the chemical reagents used for synthesis and trace contaminants in tubing, valves and fittings. A major component of contamination was nitrate from irradiation of dissolved nitrogen gas in the target water.

  12. Sources of carrier F-19 in F-18 fluoride

    NASA Astrophysics Data System (ADS)

    Link, J. M.; Shoner, S. C.; Krohn, K. A.

    2012-12-01

    Fluorine-18 is used for many PET radiopharmaceuticals. Theoretically 18F should be carrier free and a good candidate for nanochemistry. However, 18F has 10 to 1000 times more stable fluorine atoms than radioactive atoms. In order to understand the source of carrier fluoride and other ions associated with 18F radiosynthesis, anion concentrations of different components of 18F target systems as well as solvents and chemicals used in radiosynthesis were measured. Results: The enriched water used for production of 18F had low levels of anions. In general, the sources of anions, particularly of fluoride, were the chemical reagents used for synthesis and trace contaminants in tubing, valves and fittings. A major component of contamination was nitrate from irradiation of dissolved nitrogen gas in the target water.

  13. Adsorption of fluoride, phosphate, and arsenate ions on a new type of ion exchange fiber.

    PubMed

    Ruixia, Liu; Jinlong, Guo; Hongxiao, Tang

    2002-04-15

    A new type of ion exchange fiber for the removal of fluoride, phosphate, and arsenate ions has been developed. A batch adsorption technique for investigating adsorption kinetic and equilibrium parameters and determining pH adsorption edges is applied. It is shown that the adsorption properties of the ion exchange fiber for fluoride, phosphate, and arsenate ions depend on the pH value and anion concentration. The adsorption of arsenate on the sorbent reaches a maximum of 97.9% in the pH value range of 3.5 to 7.0. The adsorption percentage of phosphate is more than 99% in the pH range of 3.0 to 5.5. The adsorption of fluoride on the ion exchange fiber is found to be 90.4% at pH 3.0. The Freundlich model can describe the adsorption equilibrium data of fluoride, arsenate, and phosphate anions. The sorption of the three anions on the ion exchange fiber is a rapid process, and the adsorption kinetic data can be simulated very well by the pseudo-second-order rate equation. The column performance is carried out to assess the applicability of the ion exchange fiber for the removal of fluoride, phosphate, and arsenate ions from synthetic wastewaters with satisfactory removal efficiency. The desorption experiment shows that fluoride ion sorbed by the fiber column can be quantitatively desorbed with 5 mL of 0.50 mol/L NaOH at elution rate of 1 mL/min, and 30 mL of NaOH is necessary for the quantitative recovery of phosphate and arsenate ions.

  14. F 3 - molecular ions in fluoride crystals

    NASA Astrophysics Data System (ADS)

    Radzhabov, E. A.

    2016-02-01

    The UV absorption spectra of F 3 - molecular ions in LaF3, SrF2, CaF2, and BaF2 crystals doped with rare-earth elements are studied. Comparison of radiation-colored and additively colored crystals reveals the absorption bands of F 3 - hole centers in the region near 6 eV. Nonempirical calculations of optical transitions agree well with experimental results.

  15. Simple preparation of new [(18) F]F-labeled synthetic amino acid derivatives with two click reactions in one-pot and SPE purification.

    PubMed

    Yook, Cheol-Min; Lee, Sang Ju; Oh, Seung Jun; Ha, Hyun-Joon; Lee, Jong Jin

    2015-06-30

    New [(18) F]fluorinated 1,2,3-triazolyl amino acid derivatives were efficiently prepared from Huisgen 1,3-dipolar cycloaddition reactions, well known as click reaction. We developed two simultaneous click reactions in one-pot with a simple solid-phase extraction (SPE) purification method. [(18) F]fluoro-1-propyne was obtained at a 45% non-decay corrected radiochemical yield based on the [(18) F]fluoride ion. The one-pot and simultaneous two click reactions were performed with unprotected azido-alkyl amino acid, [(18) F]fluoro-1-propyne, and lipophilic additive alkyne to produce three synthetic amino acid derivatives, AMC-101 ([(18) F]-6a), AMC-102 ([(18) F]-6b), and AMC-103 ([(18) F]-6c) with 29%, 28%, and 24% of non-decay corrected radiochemical yields, respectively. All radiotracers indicated that radiochemical purities were >95% without any residual organic solvent. Our new method involving two click reactions in one-pot showed high radiochemical and chemical purity by easy removal of the residual precursor from the simultaneous two click reactions.

  16. Mn-salen catalysed benzylic C-H activation for the synthesis of aryl [(18)F]CF3-containing PET probes.

    PubMed

    Carroll, L; Evans, H L; Spivey, A C; Aboagye, E O

    2015-05-18

    The development of a Mn-salen complex catalysed oxidative benzylic fluorination of non-activated C-H bonds using [(18)F]fluoride is described for installation of [(18)F]CHRF, [(18)F]CR2F and particularly [(18)F]CF3 containing groups in the presence of other functional groups.

  17. One-step 18F labeling of biomolecules using organotrifluoroborates

    PubMed Central

    Liu, Zhibo; Lin, Kuo-Shyan; Bénard, François; Pourghiasian, Maral; Kiesewetter, Dale O; Perrin, David M; Chen, Xiaoyuan

    2017-01-01

    Herein we present a general protocol for the functionalization of biomolecules with an organotrifluoroborate moiety so that they can be radiolabeled with aqueous 18F fluoride (18F−) and used for positron emission tomography (PET) imaging. Among the β+-emitting radionuclides, fluorine-18 (18F) is the isotope of choice for PET, and it is produced, on-demand, in many hospitals worldwide. Organotrifluoroborates can be 18F-labeled in one step in aqueous conditions via 18F–19F isotope exchange. This protocol features a recently designed ammoniomethyltrifluoroborate, and it describes the following: (i) a synthetic strategy that affords modular synthesis of radiolabeling precursors via a copper-catalyzed ‘click’ reaction; and (ii) a one-step 18F-labeling method that obviates the need for HPLC purification. Within 30 min, 18F-labeled PET imaging probes, such as peptides, can be synthesized in good chemical and radiochemical purity (>98%), satisfactory radiochemical yield of 20–35% (n > 20, non-decay corrected) and high specific activity of 40–111 GBq/µmol (1.1–3.0 Ci/µmol). The entire procedure, including the precursor preparation and 18F radiolabeling, takes 7–10 d. PMID:26313478

  18. Synthesis of 2'-deoxy-2'-[18F]fluoro-beta-D-arabinofuranosyl nucleosides, [18F]FAU, [18F]FMAU, [18F]FBAU and [18F]FIAU, as potential PET agents for imaging cellular proliferation. Synthesis of [18F]labelled FAU, FMAU, FBAU, FIAU.

    PubMed

    Mangner, Thomas J; Klecker, Raymond W; Anderson, Lawrence; Shields, Anthony F

    2003-04-01

    An efficient and reliable synthesis of 2'-deoxy-2'-[(18)F]fluoro-beta-D-arabinofuranosyl nucleosides is presented. Overall decay-corrected radiochemical yields of 35-45% of 4 analogs, FAU, FMAU, FBAU and FIAU are routinely obtained in >98% radiochemical purity and with specific activities of greater than 3 Ci/micromol (110 MBq/micromol) in a synthesis time of approximately 3 hours. When approximately 220 mCi (8.15 GBq) of starting [(18)F]fluoride is used, 25 -30 mCi (0.93 -1.11 GBq) of product (enough to image two patients sequentially) is typically obtained.

  19. Removal of fluoride ions from water by adsorption onto carbonaceous materials produced from coffee grounds.

    PubMed

    Ogata, Fumihiko; Tominaga, Hisato; Yabutani, Hitoshi; Kawasaki, Naohito

    2011-01-01

    Carbonaceous material for the removal of fluoride ions from water was prepared from coffee grounds (CGs) by calcination and subsequent HCl treatment. The characteristics of the CGs, including the surface area, mean pore diameter, pore volume, and surface functional groups were determined, and the morphological characteristics were evaluated using scanning electron microscopy. The adsorption isotherms, saturated amount of fluoride ions adsorbed, and the effect of contact time and temperature on the adsorption of fluoride ions were investigated for a sample of tap water. The specific surface area of CG calcined at 600° (CG600) was larger than that of CGs calcined at 400, 800, and 1000°. Phenolic, lactonic, and carboxyl groups were detected on the CG600 surface. The adsorption capacity of the carbonized CGs for fluoride was ranked in the order CG400 < CG1000 < CG800 < CG600 (where the numeral indicates the carbonization temperature), whereas virgin CG and CG600-NAT (not treated with hydrochloric acid solution) did not exhibit any adsorption ability for fluoride ions. The amount of fluoride ions adsorbed onto CG600 increased with increasing temperature and was consistent with chemical adsorption. The mechanism of adsorption of fluoride ions onto CG600 proceeded via ion exchange with chloride ions (1:1) present on the surface of CG600. The adsorption isotherms were fitted to the Freundlich and Langmuir equations. Moreover, CG600 showed an acceptable adsorption capacity for fluoride ions present in tap water.

  20. .sup.18 F-4-Fluoroantipyrine

    DOEpatents

    Shiue, Chyng-Yann; Wolf, Alfred P.

    1984-03-13

    The novel radioactive compound .sup.18 F-4-fluoroantipyrine having high specific activity which can be used in nuclear medicine in diagnostic applications, prepared by the direct fluorination of antipyrine in acetic acid with radioactive fluorine at room temperature and purifying said radioactive compound by means of gel chromatography with ethyl acetate as eluent is disclosed. The non-radioactive 4-fluoroantipyrine can also be prepared by the direct fluorination of antipyrine in acetic acid with molecular fluorine at room temperature and purified by means of gel chromotography with ethyl acetate eluent.

  1. High yield synthesis of 6-(18F)fluoro-L-dopa

    SciTech Connect

    Chirakal, R.; Firnau, G.; Garnett, E.S.

    1986-03-01

    The radiofluorination of L-dopa with (/sup 18/F)F2 was investigated with the purpose of improving the yield of 6-(/sup 18/F)fluoro-L-dopa. When boron trifluoride was added to the reaction mixture in hydrogen fluoride (HF), the yield was increased threefold. Nine millicuries of 6-(/sup 18/F)fluoro-L-dopa were produced from 100 mCi (/sup 18/F)F2 routinely and reliably after 2 hr of preparation. If acetonitrile or water were substituted for HF, little or no 6-fluoro-L-dopa was made.

  2. 21-(/sup 18/F)fluoro-16 alpha-ethyl-19-norprogesterone: synthesis and target tissue selective uptake of a progestin receptor based radiotracer for positron emission tomography

    SciTech Connect

    Pomper, M.G.; Katzenellenbogen, J.A.; Welch, M.J.; Brodack, J.W.; Mathias, C.J.

    1988-07-01

    We have synthesized 21-(/sup 18/F)fluoro-16 alpha-ethyl-19-norprogesterone (FENP), a high affinity ligand for the progesterone receptor, labeled with the positron-emitting radionuclide fluorine-18 (t1/2 = 110 min). The synthesis proceeds in two steps from 21-hydroxy-16 alpha-ethyl-19-norprogesterone and involves (/sup 18/F)fluoride ion displacement of the 21-trifluoromethanesulfonate (21-triflate). This material is purified by HPLC and is obtained in 4-30% overall yield (decay corrected) within 40 min after the end of bombardment to produce (/sup 18/F)fluoride ion. The effective specific activity, determined by competitive radioreceptor binding assays, is 700-1400 Ci/mmol. In vivo, (/sup 18/F)FENP demonstrates highly selective, receptor-mediated uptake by the uterus of estrogen-primed rats; the uterus to blood and uterus to muscle ratios were respectively 26 and 16 at 1 h and 71 and 41 at 3 h after injection. The high target tissue selectivity of this uptake suggests that this compound may be useful for the in vivo imaging of progestin target tissues and receptor-rich tumors (such as human breast tumors) by positron emission tomography.

  3. Removing Fluoride Ions with Continously Fed Activated Alumina.

    ERIC Educational Resources Information Center

    Wu, Yeun C.; Itemaking, Isara Cholapranee

    1979-01-01

    Discussed is the mathematical basis for determining fluoride removal during water treatment with activated alumina. The study indicates that decreasing particle size decreases the pore diffusion effect and increases fluoride removal. (AS)

  4. A Fully-automated One-pot Synthesis of [18F]Fluoromethylcholine with Reduced Dimethylaminoethanol Contamination via [18F]Fluoromethyl Tosylate

    PubMed Central

    Rodnick, Melissa E.; Brooks, Allen F.; Hockley, Brian G.; Henderson, Bradford D.; Scott, Peter J. H.

    2013-01-01

    Introduction A novel one-pot method for preparing [18F]fluoromethylcholine ([18F]FCH) via in situ generation of [18F]fluoromethyl tosylate ([18F]FCH2OTs), and subsequent [18F]fluoromethylation of dimethylaminoethanol (DMAE), has been developed. Methods [18F]FCH was prepared using a GE TRACERlab FXFN, although the method should be readily adaptable to any other fluorine-18 synthesis module. Initially ditosylmethane was fluorinated to generate [18F]FCH2OTs. DMAE was then added and the reaction was heated at 120°C for 10 min to generate [18F]FCH. After this time, reaction solvent was evaporated, and the crude reaction mixture was purified by solid-phase extraction using C18-Plus and CM-Light Sep-Pak cartridges to provide [18F]FCH formulated in USP saline. The formulated product was passed through a 0.22 μm filter into a sterile dose vial, and submitted for quality control testing. Total synthesis time was 1.25 hours from end-of-bombardment. Results Typical non-decay-corrected yields of [18F]FCH prepared using this method were 91 mCi (7% non-decay corrected based upon ~1.3 Ci [18F]fluoride), and doses passed all other quality control (QC) tests. Conclusion A one-pot liquid-phase synthesis of [18F]FCH has been developed. Doses contain extremely low levels of residual DMAE (31.6 μg / 10 mL dose or ~3 ppm) and passed all other requisite QC testing, confirming their suitability for use in clinical imaging studies. PMID:23665261

  5. 18F-AFETP, 18F-FET, and 18F-FDG Imaging of Mouse DBT Gliomas

    PubMed Central

    Sai, Kiran Kumar Solingapuram; Huang, Chaofeng; Yuan, Liya; Zhou, Dong; Piwnica-Worms, David; Garbow, Joel R.; Engelbach, John A.; Mach, Robert H.; Rich, Keith M.; McConathy, Jonathan

    2013-01-01

    The goal of this study was to evaluate the 18F-labeled nonnatural amino acid (S)-2-amino-3-[1-(2-18F-fluoroethyl)-1H-[1,2,3]triazol-4-yl]propanoic acid (18F-AFETP) as a PET imaging agent for brain tumors and to compare its effectiveness with the more-established tracers O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) and 18F-FDG in a murine model of glioblastoma. The tracer 18F-AFETP is a structural analog of histidine and is a lead compound for imaging cationic amino acid transport, a relatively unexplored target for oncologic imaging. Methods 18F-AFETP was prepared using the click reaction. BALB/c mice with intracranially implanted delayed brain tumor (DBT) gliomas (n = 4) underwent biodistribution and dynamic small-animal PET imaging for 60 min after intravenous injection of 18F-AFETP. Tumor and brain uptake of 18F-AFETP were compared with those of 18F-FDG and 18F-FET through small-animal PET analyses. Results 18F-AFETP demonstrated focally increased uptake in tumors with good visualization. Peak tumor uptake occurred within 10 min of injection, with stable or gradual decrease over time. All 3 tracers demonstrated relatively high uptake in the DBTs throughout the study. At late time points (47.5–57.5 min after injection), the average standardized uptake value with 18F-FDG (1.9 ± 0.1) was significantly greater than with 18F-FET (1.1 ± 0.1) and 18F-AFETP (0.7 ± 0.2). The uptake also differed substantially in normal brain, with significant differences in the standardized uptake values at late times among 18F-FDG (1.5 ± 0.2), 18F-FET (0.5 ± 0.05), and 18F-AFETP (0.1 ± 0.04). The resulting average tumor-to-brain ratio at the late time points was significantly higher for 18F-AFETP (7.5 ± 0.1) than for 18F-FDG (1.3 ± 0.1) and 18F-FET (2.0 ± 0.3). Conclusion 18F-AFETP is a promising brain tumor imaging agent, providing rapid and persistent tumor visualization, with good tumor–to–normal-brain ratios in the DBT glioma model. High tumor-to-brain, tumor

  6. Analytical Determination of Fluoride Ion Using Gran's Semi-Antilog Plot.

    ERIC Educational Resources Information Center

    Barnhard, Ralph J.

    1983-01-01

    A quantitative determination for fluoride ion using a commercially available fluoride electrode is described. The procedure referred to as known-addition is employed with the data processed on Gran's Plot Paper. Background information, experimental procedures, and advantages/disadvantages of the method are discussed. (JN)

  7. Efficient Automated Syntheses of High Specific Activity 6-[18F]Fluorodopamine Using A Diaryliodonium Salt Precursor

    PubMed Central

    Neumann, Kiel D.; Qin, Linlin; Vāvere, Amy L.; Shen, Bin; Miao, Zheng; Chin, Frederick T.; Shulkin, Barry L.; Snyder, Scott E.; DiMagno, Stephen G.

    2015-01-01

    6-[18F]Fluorodopamine, 6-[18F]F-DA, is a PET radiopharmaceutical used to image sympathetic cardiac innervation and neuroendocrine tumors. Imaging with 6-[18F]F-DA is constrained, in part, by the bioactivity and neurotoxicity of 6-[19F]fluorodopamine. Furthermore, routine access to this radiotracer is limited by the inherent difficulty of incorporation of [18F]fluoride into electron-rich aromatic substrates. We describe the simple and direct preparation of high specific activity (SA) 6-[18F]F-DA from no-carrier-added (n.c.a.) [18F]fluoride. Incorporation of n.c.a. [18F]fluoride into a diaryliodonium salt precursor was achieved in 50–75% radiochemical yields (decay-corrected to EOB). Synthesis of 6-[18F]F-DA on the IBA Synthera® and GE TRACERlab FX-FN automated platforms gave 6-[18F]F-DA in >99% chemical and radiochemical purities after HPLC purification. The final non-corrected yields of 6-[18F]F-DA were 25 ± 4% (n = 4, 65 min) and 31 ± 6% (n = 3, 75 min) using the Synthera and TRACERlab modules, respectively. Efficient access to high SA 6-[18F]F-DA from a diaryliodonium salt precursor and n.c.a. [18F]fluoride is provided by a relatively subtle change in reaction conditions; replacement of a polar aprotic solvent (acetonitrile) with a relatively nonpolar solvent (toluene) during the critical radiofluorination reaction. Implementation of this process on common radiochemistry platforms should make 6-[18F]fluorodopamine readily available to the wider imaging community. PMID:26695865

  8. Crystal structures of a double-barrelled fluoride ion channel

    PubMed Central

    Stockbridge, Randy B.; Kolmakova-Partensky, Ludmila; Shane, Tania; Koide, Akiko; Koide, Shohei; Miller, Christopher; Newstead, Simon

    2016-01-01

    To contend with hazards posed by environmental fluoride, microorganisms export this anion through F--specific ion channels of the Fluc family1–4. Since the recent discovery of Fluc channels, numerous idiosyncratic features of these proteins have been unearthed, including extreme selectivity for F- over Cl- and dual-topology dimeric assembly5–6. To understand the chemical basis for F- permeation and how the antiparallel subunits convene to form a F--selective pore, we solved crystal structures of two bacterial Fluc homologues in complex with three different monobody inhibitors, with and without F- present, to a maximum resolution of 2.1 Å. The structures reveal a surprising “double-barrelled” channel architecture in which two F- ion pathways span the membrane and the dual-topology arrangement includes a centrally coordinated cation, most likely Na+. F- selectivity is proposed to arise from the very narrow pores and an unusual anion coordination that exploits the quadrupolar edges of conserved phenylalanine rings. PMID:26344196

  9. New Dioxaborolane Chemistry Enables [(18)F]-Positron-Emitting, Fluorescent [(18)F]-Multimodality Biomolecule Generation from the Solid Phase.

    PubMed

    Rodriguez, Erik A; Wang, Ye; Crisp, Jessica L; Vera, David R; Tsien, Roger Y; Ting, Richard

    2016-05-18

    New protecting group chemistry is used to greatly simplify imaging probe production. Temperature and organic solvent-sensitive biomolecules are covalently attached to a biotin-bearing dioxaborolane, which facilitates antibody immobilization on a streptavidin-agarose solid-phase support. Treatment with aqueous fluoride triggers fluoride-labeled antibody release from the solid phase, separated from unlabeled antibody, and creates [(18)F]-trifluoroborate-antibody for positron emission tomography and near-infrared fluorescent (PET/NIRF) multimodality imaging. This dioxaborolane-fluoride reaction is bioorthogonal, does not inhibit antigen binding, and increases [(18)F]-specific activity relative to solution-based radiosyntheses. Two applications are investigated: an anti-epithelial cell adhesion molecule (EpCAM) monoclonal antibody (mAb) that labels prostate tumors and Cetuximab, an anti-epidermal growth factor receptor (EGFR) mAb (FDA approved) that labels lung adenocarcinoma tumors. Colocalized, tumor-specific NIRF and PET imaging confirm utility of the new technology. The described chemistry should allow labeling of many commercial systems, diabodies, nanoparticles, and small molecules for dual modality imaging of many diseases.

  10. Efficient radiosynthesis of 3′-deoxy-3′-[18F]fluorothymidine using electrowetting-on-dielectric digital microfluidic chip

    PubMed Central

    Javed, Muhammad Rashed; Chen, Supin; Kim, Hee-Kwon; Wei, Liu; Czernin, Johannes; Kim, Chang-Jin “CJ”; van Dam, R. Michael; Keng, Pei Yuin

    2015-01-01

    Access to diverse PET tracers for preclinical and clinical research remains a major obstacle to research in cancer and other diseases research. The prohibitive cost and limited availability of tracers could be alleviated by microfluidic radiosynthesis technologies combined with high-yield microscale radiosynthetic method. In this report, we demonstrate the multistep synthesis of 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) with high yield on an electrowetting on dielectric (EWOD) microfluidic radiosynthesizer, previously developed in our group. We have identified and established several parameters that are most critical in the microscale radiosynthesis such as the reaction time, reagent concentration, and molar ratios, to successfully synthesize [18F]FLT in this compact platform. Methods [18F]FLT was synthesized from the 3-N-Boc-1-[5-O-(4,4′-dimethoxytrityl)-3-O-nosyl-2-deoxy-β-d-lyxofuranosyl] thymine precursor on the EWOD chip starting from the first solvent exchange and [18F]fluoride ion activation step to the final deprotection step. The fluorination reaction was performed in a mixture of thexyl alcohol and DMSO. The crude product after deprotection was collected from the chip and purified on a custom-made solid phase extraction (SPE) cartridge and subjected to quality control testing. The purified [18F]FLT was suitable for microPET studies in multiple nude mice xenografted with the A431 carcinoma cell line. Results [18F]FLT was successfully synthesized on the EWOD microdevice coupled with an off-chip SPE purification with a decayed-corrected radiochemical yield of 63±5% (n=5) and passed all of the quality control test required by the United States Pharmacopeia for radiotracers to be injected into humans. We have successfully demonstrated the synthesis of several batches of [18F]FLT on EWOD starting with ∼ 333 MBq of radioactivity and obtained up to 52 MBq (non-decay corrected) of [18F]FLT upon cartridge purification. The specific activity of two

  11. Study of wear analysis with {sup 18}F

    SciTech Connect

    Schmidt, N.; Nolen, J.A.; Blumenthal, D.J.

    1995-08-01

    We are studying the possible use of low-energy radioactive beams for the wear analysis of various industrial components (e.g. engine parts and materials for orthopedic implants). Previous experiments with {sup 7}Be and {sup 22}Na studied components at implantation depths of several tens of micrometer. In a first series of experiments we implanted {sup 18}F ions into the surface layer, which opens the possibility to study wear in the critical first micrometer of various materials. {sup 18}F was produced via the p({sup 18}O, {sup 18}F)n reaction at E{sub 18}{sub O} = 110 MeV using a 1.22-mg/cm{sub 2} polypropylene foil as a hydrogen target. The {sup 18}F{sup 9+} ions were separated at {theta}=0{degrees} from the incident {sup 18}O{sup 8+} beam with the split-pole spectrograph. In order to allow for a rapid change of irradiation samples, the {sup 18}F ions penetrated a thin HAVAR foil and were implanted into the sample which was located outside the vacuum chamber behind the pressure window. The depth distribution of the {sup 18}F was tested by implantation into a series of 1.5-{mu} thick Mylar foils which were subsequently measured with respect to their {sup 18}F activity using a Si-surface barrier detector. The localization of the {sup 18}F ions was found to be better than 1.5 {mu}. The implantation depth could be varied in the range between 1.5 {mu} - 9 {mu} by choosing the appropriate distance between pressure window and implantation sample. The wear rate was determined by measuring the (decay-corrected) decrease of the activity remaining in the sample after it was polished with Emery paper. In a first experiment the wear of stainless steel could be measured by this technique with a sensitivity of better than 100 nm. A paper describing these results is under preparation.

  12. Nucleophile Assisting Leaving Groups: A Strategy for Aliphatic 18F-Fluorination

    PubMed Central

    Lu, Shuiyu; Lepore, Salvatore D.; Li, Song Ye; Mondal, Deboprosad; Cohn, Pamela C.; Bhunia, Anjan K.; Pike, Victor W.

    2009-01-01

    A series of arylsulfonate nucleophile assisting leaving groups (NALGs) were prepared in which the metal chelating unit is attached to the aryl ring via an ether linker. These NALGs exhibited significant rate enhancements in halogenation reactions using metal halides. Studies with a NALG containing a macrocyclic ether unit suggest that rate enhancements of these nucleophilic halogenation reactions are facilitated by stabilization of charge in the transition state rather than through strong pre-complexation with metal cation. In several cases, a primary substrate containing one of the new leaving groups rivaled or surpassed the reactivity of triflates when exposed to nucleophile but was otherwise highly stable and isolable. These and previously disclosed chelating leaving groups were used in 18F-fluorination reactions using no-carrier-added [18F]fluoride ion (t1/2 = 109.7 min, β+ = 97%) in CH3CN. Under microwave irradiation and without the assistance of a cryptand, such as K2.2.2, primary substrates with select NALGs led to a substantial improvement (2 to 3 fold) in radiofluorination yields over traditional leaving groups. PMID:19572583

  13. Retention of fluoride ions from aqueous solution using porous hydroxyapatite. Structure and conduction properties.

    PubMed

    Hammari, L E L; Laghzizil, A; Barboux, P; Lahlil, K; Saoiabi, A

    2004-10-18

    Synthetic porous calcium hydroxyapatite (noted p-HAp) treated with different fluoride concentrations at room temperature in the presence of carbonate, sodium chloride and phosphate-rich media was investigated. The fluoridation rate of the porous calcium hydroxyapatite was 89% using 1 mol/L [F(-)] solution compared with 30% for crystalline hydroxyapatite (c-HAp). The high specific surface area of p-HAp (235 m(2)g(-1)) compared with c-HAp sample (47 m(2)g(-1)) has an important effect on the removal of fluoride ions from aqueous solution, when p-HAp was treated with high fluoride concentration to produce calcium fluorohydroxyapatite materials. Fluoride adsorption on porous hydroxyapatites (p-HAp) modified their structural and conduction properties.

  14. Comparison of the biological effects of {sup 18}F at different intracellular levels

    SciTech Connect

    Kashino, Genro; Hayashi, Kazutaka; Douhara, Kazumasa; Kobashigawa, Shinko; Mori, Hiromu

    2014-11-07

    Highlights: • We estimated the inductions of DNA DSB in cell treated with {sup 18}F-FDG. • We found that inductions of DNA DSB are dependent on accumulation of {sup 18}F in cell. • Accumulation of {sup 18}F in cell may be indispensable for risk estimation of PET. - Abstract: We herein examined the biological effects of cells treated with {sup 18}F labeled drugs for positron emission tomography (PET). The relationship between the intracellular distribution of {sup 18}F and levels of damaged DNA has yet to be clarified in detail. We used culture cells (Chinese Hamster Ovary cells) treated with two types of {sup 18}F labeled drugs, fluorodeoxyglucose (FDG) and fluorine ion (HF). FDG efficiently accumulated in cells, whereas HF did not. To examine the induction of DNA double strand breaks (DSB), we measured the number of foci for 53BP1 that formed at the site of DNA DSB. The results revealed that although radioactivity levels were the same, the induction of 53BP1 foci was stronger in cells treated with {sup 18}F-FDG than in those treated with {sup 18}F-HF. The clonogenic survival of cells was significantly lower with {sup 18}F-FDG than with {sup 18}F-HF. We concluded that the efficient accumulation of {sup 18}F in cells led to stronger biological effects due to more severe cellular lethality via the induction of DNA DSB.

  15. CHARACTERIZATION OF THE TANK 18F SAMPLES

    SciTech Connect

    Oji, L.; Click, D.; Diprete, D.

    2009-12-17

    The Savannah River National Laboratory (SRNL) was asked by Liquid Waste Operations to characterize Tank 18F closure samples. Tank 18F slurry samples analyzed included the liquid and solid fractions derived from the 'as-received' slurry materials along with the floor scrape bottom Tank 18F wet solids. These samples were taken from Tank 18F in March 2009 and made available to SRNL in the same month. Because of limited amounts of solids observed in Tank 18F samples, the samples from the north quadrants of the tank were combined into one North Tank 18F Hemisphere sample and similarly the south quadrant samples were combined into one South Tank 18F Hemisphere sample. These samples were delivered to the SRNL shielded cell. The Tank 18F samples were analyzed for radiological, chemical and elemental components. Where analytical methods yielded additional contaminants other than those requested by the customer, these results were also reported. The target detection limits for isotopes analyzed were 1E-04 {micro}Ci/g for most radionuclides and customer desired detection values of 1E-05 {micro}Ci/g for I-129, Pa-231, Np-237, and Ra-226. While many of the minimum detection limits, as specified in the technical task request and task technical and quality assurance plans were met for the species characterized for Tank 18F, some were not met due to spectral interferences. In a number of cases, the relatively high levels of radioactive species of the same element or a chemically similar element precluded the ability to measure some isotopes to low levels. SRNL, in conjunction with the plant customer, reviewed all these cases and determined that the impacts were negligible.

  16. Indirect voltammetric detection of fluoride ions in toothpaste on a comb-shaped interdigitated microelectrode array.

    PubMed

    Cernanská, Monika; Tomcík, Peter; Jánosíková, Zuzana; Rievaj, Miroslav; Bustin, Dusan

    2011-02-15

    A novel technique based on dynamic electrochemistry for the detection of fluoride ions was developed. It is based on its strong complexation with ferric ion. Formed fluoroferric complex is cathodically inactive at the potential of the reduction of free ferric aquo ion. The voltammetric and amperometric response of platinum comb-shaped interdigitated microelectrode array is decreased after fluoride addition. This decrease serves for the quantification of fluoride ions added to the solution. The detection limit of 4.5×10(-5) mol dm(-3) was achieved when one of the segments of interdigitated microelectrode array (IDA) was used as an indicating electrode. The detection limit is about one order of magnitude lower than in the case of conventional platinum macroelectrode. In comparison with ISE electrodes this method is faster and also avoiding large error resulting from the antilogarithmization of ISE Nerstian response. The method was applied to the analysis of toothpaste.

  17. Inhibition of Chloride Induced Crevice Corrosion in Alloy 22 by Fluoride Ions

    SciTech Connect

    Carranza, R M; Rodr?guez, M A; Rebak, R B

    2005-10-09

    Alloy 22 (N06022) is highly resistant to localized corrosion. Alloy 22 may be susceptible to crevice corrosion in pure chloride (Cl{sup -}) solutions under aggressive environmental conditions. The effect of the fluoride (F{sup -}) over the crevice corrosion induced by chloride ions is still not well established. The objective of the present work was to explore the crevice corrosion resistance of this alloy to different mixtures of fluorides and chlorides. Cyclic potentiodynamic polarization (CPP) tests were conducted in deaerated aqueous solutions of pure halide ions and also in different mixtures of chloride and fluoride at 90 C and pH 6. The range of chloride concentration [Cl{sup -}] was 0.001 M {le} [Cl{sup -}] {le} 1 M and the range of molar fluoride to chloride ratio [F{sup -}]/[Cl{sup -}] was 0.1 {le} [F{sup -}]/[Cl{sup -}] {le} 10. Results showed that Alloy 22 was susceptible to crevice corrosion in all the pure chloride solutions but not in the pure fluoride solutions. Fluoride ions showed an inhibitor behavior only in mixtures with a molar ratio [F{sup -}]/[Cl{sup -}] > 2. For mixtures with a molar ratio [F{sup -}]/[Cl{sup -}] of 7 and 10 the inhibition of crevice corrosion was complete.

  18. Combinatorial incorporation of fluoride and cobalt ions into calcium phosphates to stimulate osteogenesis and angiogenesis.

    PubMed

    Birgani, Zeinab Tahmasebi; Gharraee, Nazli; Malhotra, Angad; van Blitterswijk, Clemens A; Habibovic, Pamela

    2016-02-29

    Bone healing requires two critical mechanisms, angiogenesis and osteogenesis. In order to improve bone graft substitutes, both mechanisms should be addressed simultaneously. While the individual effects of various bioinorganics have been studied, an understanding of the combinatorial effects is lacking. Cobalt and fluoride ions, in appropriate concentrations, are known to individually favor the vascularization and mineralization processes, respectively. This study investigated the potential of using a combination of fluoride and cobalt ions to simultaneously promote osteogenesis and angiogenesis in human mesenchymal stromal cells (hMSCs). Using a two-step biomimetic method, wells of tissue culture plates were coated with a calcium phosphate (CaP) layer without or with the incorporation of cobalt, fluoride, or both. In parallel, hMSCs were cultured on uncoated well plates, and cultured with cobalt and/or fluoride ions within the media. The results revealed that cobalt ions increased the expression of angiogenic markers, with the effects being stronger when the ions were added as a dissolved salt in cell medium as compared to incorporation into CaP. Cobalt ions generally suppressed the ALP activity, the expression of osteogenic genes, and the level of mineralization, regardless of delivery method. Fluoride ions, individually or in combination with cobalt, significantly increased the expression of many of the selected osteogenic markers, as well as mineral deposition. This study demonstrates an approach to simultaneously target the two essential mechanisms in bone healing: angiogenesis and osteogenesis. The incorporation of cobalt and fluoride into CaPs is a promising method to improve the biological performance of fully synthetic bone graft substitutes.

  19. Comparison of aluminum modified natural materials in the removal of fluoride ions.

    PubMed

    Teutli-Sequeira, A; Solache-Ríos, M; Martínez-Miranda, V; Linares-Hernández, I

    2014-03-15

    The removal behaviors of fluoride ions from aqueous solutions and drinking water by aluminum modified hematite, zeolitic tuff and calcite were determined. Drinking water containing naturally 8.29 mg of fluoride ions per liter was characterized. The hematite, zeolitic tuff and calcite were aluminum modified by an electrochemical method. The effects of contact time and the dose of adsorbent were determined. The PZC (point of zero charge) values for aluminum modified hematite, zeolitic tuff and calcite were 6.2, 5.8 and 8.4, respectively. Adsorption kinetic data were best fitted to pseudo-second-order and Elovich models and equilibrium data to Langmuir-Freundlich isotherm model. The highest fluoride sorption capacities (10.25 and 1.16 mg/g for aqueous solutions and drinking water respectively) were obtained for aluminum modified zeolite with an adsorbent dosage of 10 g/L and an initial F(-) concentration of 9 and 8.29 mg/L for aqueous solutions and drinking water respectively (the final concentrations were 0.08 and 0.7 mg/L respectively). The main mechanism involved in the adsorption of fluoride ions is chemisorption on heterogeneous materials according to the results obtained by fitting the data to kinetic and isotherm models respectively. Aluminum modified zeolitic tuff showed the best characteristics for the removal of fluoride ions from water.

  20. 18F-Fluorodeoxyglycosylamines: Maillard reaction of 18F-fluorodeoxyglucose with biological amines.

    PubMed

    Baranwal, Aparna; Patel, Himika H; Mukherjee, Jogeshwar

    2014-02-01

    The Maillard reaction of sugars and amines resulting in the formation of glycosylamines and Amadori products is of biological significance, for drug delivery, role in central nervous system, and other potential applications. We have examined the interaction of (18) F-fluorodeoxyglucose ((18) F-FDG) with biological amines to study the formation of (18) F-fluorodeoxyglycosylamines ((18) F-FDGly). Respective amines N-allyl-2-aminomethylpyrrolidine (NAP) and 2-(4'-aminophenyl)-6-hydroxybenzothiazole (PIB precursor) were mixed with FDG to provide glycosylamines, FDGNAP and FDGBTA. Radiosynthesis using (18) F-FDG (2-5 mCi) was carried out to provide (18) F-FDGNAP and (18) F-FDGBTA. Binding of FDGBTA and (18) F-FDGBTA was evaluated in human brain sections of Alzheimer's disease (AD) patients and control subjects using autoradiography. Both FDGNAP and FDGBTA were isolated as stable products. Kinetics of (18) F-FDGNAP reaction indicated a significant product at 4 h (63% radiochemical yield). (18) F-FDGBTA was prepared in 57% yield. Preliminary studies of FDGBTA showed displacement of (3) H-PIB (reduced by 80%), and (18) F-FDGBTA indicated selective binding to Aβ-amyloid plaques present in postmortem AD human brain, with a gray matter ratio of 3 between the AD patients and control subjects. We have demonstrated that (18) F-FDG couples with amines under mild conditions to form (18) F-FDGly in a manner similar to click chemistry. Although these amine derivatives are stable in vitro, stability in vivo and selective binding is under investigation.

  1. Association between osteogenesis and inflammation during the progression of calcified plaque as evaluated by combined (18)F-NaF and (18)F-FDG PET/CT.

    PubMed

    Li, Xiang; Heber, Daniel; Cal-Gonzales, Jacobo; Karanikas, Georgios; Mayerhoefer, Marius E; Rasul, Sazan; Beitzke, Dietrich; Zhang, Xiaoli; Agis, Hermine; Mitterhauser, Markus; Wadsak, Wolfgang; Beyer, Thomas; Loewe, Christian; Hacker, Marcus

    2017-02-23

    Background and Aim:(18)F-fluorodeoxyglucose ((18)F-FDG) is the most widely validated positron emission tomography (PET) tracer for the evaluation of atherosclerotic inflammation. (18)F-sodium fluoride ((18)F-NaF) has also been recently considered a potential novel biomarker of osteogenesis in atherosclerosis. We aimed to analyze the association between inflammation and osteogenesis at different stages of atherosclerosis, as well as the interrelationship between these two processes during disease progression. Methods: Thirty-four myeloma patients underwent (18)F-NaF and (18)F-FDG PET/computed tomography (CT) examinations. Three groups (non-calcified; mildly calcified; and severely calcified lesions) were divided based on the calcium density as measured in Hounsfield units (HU) by CT. Tissue-to-background ratios (TBR) were determined from PET for both tracers. The association between inflammation and the osteogenesis during atherosclerosis progression was evaluated in 19 patients who had at least two examinations with both tracers. Results: There were significant correlations between the TBRmax values of the two tracers (Spearman's r = 0.5, P < 0.01, Pearson r = 0.4, P < 0.01) in the 221 lesions at baseline. In non-calcified lesions, highest uptake of both tracers was observed, but without any correlation between both tracers (Pearson r = 0.06, P = 0.76). Compared to non-calcified plaques, concordant significantly lower accumulation was found in mildly calcified plaques, with good correlation between the tracers (Pearson r = 0.7, P < 0.01). In addition, there was enhanced osteogenesis-derived (18)F-NaF uptake, and regressive inflammation-derived (18)F-FDG uptake in severely calcified lesions (Pearson r = 0.4, P < 0.01). During follow-up, there was an increased calcium density and an increased mean (18)F-NaF uptake observed, while the mean (18)F-FDG uptake decreased. The majority of non-calcified (86%) and mildly calcified (81%) lesions and 47% of severely calcified

  2. Iodonium Ylide Mediated Radiofluorination of 18F-FPEB and Validation for Human Use

    PubMed Central

    Stephenson, Nickeisha A.; Holland, Jason P.; Kassenbrock, Alina; Yokell, Daniel L.; Livni, Eli; Liang, Steven H.; Vasdev, Neil

    2016-01-01

    Translation of new methodologies for labeling non-activated aromatic molecules with fluorine-18 remains a challenge. Here, we report a one-step, regioselective, metal-free 18F-labeling method that employs a hypervalent iodonium(III) ylide precursor, to prepare the radiopharmaceutical 18F-FPEB. Methods Automated radiosynthesis of 18F-FPEB was achieved by reaction of the ylide precursor (4 mg) with 18F-NEt4F in DMF at 80 °C for 5 minutes, and formulated for injection within 1 hour. Results 18F-FPEB was synthesized in 15 – 25% (n = 3) uncorrected radiochemical yields relative to 18F-fluoride, with specific activities of 666 ± 51.8 GBq/μmol (18 ± 1.4 Ci/μmol) at the end-of-synthesis (EOS). The radiopharmaceutical was validated for human use. Conclusions Radiofluorination of iodonium (III) ylides proved to be an efficient radiosynthetic strategy for synthesis of 18F-labeled radiopharmaceuticals. PMID:25655630

  3. Al[18F]NOTA-T140 Peptide for Noninvasive Visualization of CXCR4 Expression

    PubMed Central

    Yan, Xuefeng; Niu, Gang; Wang, Zhe; Yang, Xiangyu; Kiesewetter, Dale O.; Jacobson, Orit; Shen, Baozhong; Chen, Xiaoyuan

    2017-01-01

    Purpose Chemokine receptor CXCR4 plays an important role in tumor aggressiveness, invasiveness, and metastasis formation. Quantification of CXCR4 expression by tumors may have an impact on prediction and evaluation of tumor response to therapies. In this study, we developed a robust and straightforward F-18 labeling route of T140, a CXCR4 peptide-based antagonist. Procedures T140 derivative was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA) and labeled with Al[18F]. Al[18F]NOTA-T140 was evaluated in vitro in cell-based assay and stability in mouse serum and in vivo using CXCR4 positive and negative tumor xenograft models. Results Labeling of Al[18F]NOTA-T140 was completed within 30 min with a radiochemical yield of 58±5.3 % at the end of synthesis, based on fluoride-18 activity. Al[18F]NOTA-T140 accumulated in CHO-CXCR4 positive but not negative tumors. Al[18F]NOTA-T140 uptake in the tumors correlated with CXCR4 protein expression. Moreover, Al[18F]NOTA-T140 had high accumulation in CXCR4-positive metastatic tumors. Conclusions The simplicity of Al[18F]NOTA-T140 labeling along with its properties to specifically image CXCR4 expression by tumors warrant further clinical application for the diagnosis of CXCR4 clinically. PMID:26126597

  4. Two years of experience with the [ 18F]FDG production module

    NASA Astrophysics Data System (ADS)

    Kim, Sang Wook; Hur, Min Goo; Chai, Jong-Seo; Park, Jeong Hoon; Yu, Kook Hyun; Jeong, Cheol Ki; Lee, Goung Jin; Min, Young Don; Yang, Seung Dae

    2007-08-01

    Chemistry module for a conventional [18F]FDG production by using tetrabutylammonium bicarbonate (TBA) and an acidic hydrolysis has been manufactured and evaluated. In this experiment, 75 mM (pH 7.5-7.8) of TBA solution and a ca. 2-curies order of [18F]-fluoride have been used for the evaluation. The commercial acidic purification cartridge was purchased from GE or UKE. The operation system (OS) was programmed with Lab-View which was selected because of its easy customization of the OS. Small sized solenoid valves (Burkert; type 6124) were selected to reduce the module dimensions (W 350 × D 270 × H 250). The total time for the synthesis of [18F]FDG was 30 ± 3 min. The production yield of [18F]FDG was 60 ± 2% on an average at EOS, with the decay uncorrected. This experimental data show that the traditional chemistry module can provide a good [18F]FDG production yield by optimizing the operational conditions. The radiochemical purity, radionuclidic purity, acidity, residual solvent, osmolality and endotoxin were determined to assess the quality of [18F]FDG. The examined contents for the quality control of [18F]FDG were found to be suitable for a clinical application.

  5. Kinetics of sorption of niobium ions by anion-exchangers from mixed chloride-fluoride solutions

    SciTech Connect

    Rychkov, V.N.; Pakholkov, V.S.; Kuznetsova, L.D.

    1987-08-10

    The authors showed earlier on the basis of experimental and calculated data obtained in studies of ion-exchange equilibrium that the sorbability and composition of sorbed niobium ions are determined by the content of hydrofluoric acid in mixed chloride-fluoride solutions. Variation of the ionic state of niobium in these solutions should also influence the rate of ion exchange. In this communication they examine the results of a study of the kinetics of exchange of niobium ions on AV-17 x 8, EDE-10P, and AN-2F anion-exchange resins in fluoride-containing solutions. Kinetic curves for sorption of niobium ions and the results of their evaluation are presented.

  6. Fluoride ion contamination in the groundwater of Mithi sub-district, the Thar Desert, Pakistan

    NASA Astrophysics Data System (ADS)

    Rafique, Tahir; Naseem, Shahid; Bhanger, Muhammad I.; Usmani, Tanzil H.

    2008-11-01

    Groundwater samples were collected from various localities of Mithi sub-district of the Thar Desert of Pakistan and analysed for fluoride ion along with other chemical parameters. The area is mainly covered by sand dunes and kaolin/granite at variable depths. Results showed that collected water samples were severely contaminated by the presence of fluoride ion and most of the samples have higher concentration than prescribed WHO standards (1.5 mg/l) for drinking water. Fluoride ion concentrations ranged between 0.09 and 11.63 mg/l with mean and median values of 3.64 and 3.44 mg/l, respectively, in this area whereas, distribution pattern showed high concentrations in the vicinity of Islamkot and Mithi towns. The content of F- has also been correlated with other major ions found in the groundwater of the study area. The positive correlation of F- with Na+ and HCO3 - showed that the water with high Na+ and HCO3 - stabilizes F- ions in the groundwater of the Thar Desert. The pH versus F- plots signifies high fluoride concentration at higher pH values, implying that alkaline environment favours the replacement of exchangeable OH- with F- in the groundwater of Mithi area. The saturation indices (SI) of fluorite (CaF2) and calcite (CaCO3) in the groundwater samples showed that most of the samples are oversaturated with respect to calcite whereas majority of samples have been found under saturated with respect to fluorite. The log TDS and Na/Na+Ca ratio reflected supremacy of weathering of rocks, which promotes the availability of fluoride ions in the groundwater. Piper diagram has been used to classify the hydrofacies. In the cation triangle, all samples are Na-type, while the anion triangle reflects major dominance of Cl-type with a minor influence of HCO3 - and SO4 -.

  7. Nuclear quantum effects in water exchange around lithium and fluoride ions.

    PubMed

    Wilkins, David M; Manolopoulos, David E; Dang, Liem X

    2015-02-14

    We employ classical and ring polymer molecular dynamics simulations to study the effect of nuclear quantum fluctuations on the structure and the water exchange dynamics of aqueous solutions of lithium and fluoride ions. While we obtain reasonably good agreement with experimental data for solutions of lithium by augmenting the Coulombic interactions between the ion and the water molecules with a standard Lennard-Jones ion-oxygen potential, the same is not true for solutions of fluoride, for which we find that a potential with a softer repulsive wall gives much better agreement. A small degree of destabilization of the first hydration shell is found in quantum simulations of both ions when compared with classical simulations, with the shell becoming less sharply defined and the mean residence time of the water molecules in the shell decreasing. In line with these modest differences, we find that the mechanisms of the exchange processes are unaffected by quantization, so a classical description of these reactions gives qualitatively correct and quantitatively reasonable results. We also find that the quantum effects in solutions of lithium are larger than in solutions of fluoride. This is partly due to the stronger interaction of lithium with water molecules, partly due to the lighter mass of lithium and partly due to competing quantum effects in the hydration of fluoride, which are absent in the hydration of lithium.

  8. Nuclear quantum effects in water exchange around lithium and fluoride ions

    SciTech Connect

    Wilkins, David M.; Manolopoulos, David E.; Dang, Liem X.

    2015-02-14

    We employ classical and ring polymer molecular dynamics simulations to study the effect of nuclear quantum fluctuations on the structure and the water exchange dynamics of aqueous solutions of lithium and fluoride ions. While we obtain reasonably good agreement with experimental data for solutions of lithium by augmenting the Coulombic interactions between the ion and the water molecules with a standard Lennard-Jones ion-oxygen potential, the same is not true for solutions of fluoride, for which we find that a potential with a softer repulsive wall gives much better agreement. A small degree of destabilization of the first hydration shell is found in quantum simulations of both ions when compared with classical simulations, with the shell becoming less sharply defined and the mean residence time of the water molecules in the shell decreasing. In line with these modest differences, we find that the mechanisms of the exchange processes are unaffected by quantization, so a classical description of these reactions gives qualitatively correct and quantitatively reasonable results. We also find that the quantum effects in solutions of lithium are larger than in solutions of fluoride. This is partly due to the stronger interaction of lithium with water molecules, partly due to the lighter mass of lithium and partly due to competing quantum effects in the hydration of fluoride, which are absent in the hydration of lithium.

  9. Nuclear quantum effects in water exchange around lithium and fluoride ions

    SciTech Connect

    Wilkins, David M.; Manolopoulos, David; Dang, Liem X.

    2015-02-14

    We employ classical and ring polymer molecular dynamics simulations to study the effect of nuclear quantum fluctuations on the structure and the water exchange dynamics of aqueous solutions of lithium and fluoride ions. While we obtain reasonably good agreement with experimental data for solutions of lithium by augmenting the Coulombic interactions between the ion and the water molecules with a standard Lennard-Jones ion-oxygen potential, the same is not true for solutions of fluoride, for which we find that a potential with a softer repulsive wall gives much better agreement. A small degree of destabilization of the first hydration shell is found in quantum simulations of both ions when compared with classical simulations, with the shell becoming less sharply defined and the mean residence time of the water molecules in the shell decreasing. In line with these modest differences, we find that the mechanisms of the water exchange reactions are unaffected by quantization, so a classical description of these reactions gives qualitatively correct and quantitatively reasonable results. We also find that the quantum effects in solutions of lithium are larger than in solutions of fluoride. This is partly due to the stronger interaction of lithium with water molecules, partly due to the lighter mass of lithium, and partly due to competing quantum effects in the hydration of fluoride, which are absent in the hydration of lithium. LXD was supported by US Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences.

  10. 18F-Labeling Using Click Cycloadditions

    PubMed Central

    Ross, Tobias L.

    2014-01-01

    Due to expanding applications of positron emission tomography (PET) there is a demand for developing new techniques to introduce fluorine-18 (t1/2 = 109.8 min). Considering that most novel PET tracers are sensitive biomolecules and that direct introduction of fluorine-18 often needs harsh conditions, the insertion of 18F in those molecules poses an exceeding challenge. Two major challenges during 18F-labeling are a regioselective introduction and a fast and high yielding way under mild conditions. Furthermore, attention has to be paid to functionalities, which are usually present in complex structures of the target molecule. The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) and several copper-free click reactions represent such methods for radiolabeling of sensitive molecules under the above-mentioned criteria. This minireview will provide a quick overview about the development of novel 18F-labeled prosthetic groups for click cycloadditions and will summarize recent trends in copper-catalyzed and copper-free click 18F-cycloadditions. PMID:25003110

  11. Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with 18F positron emission tomography

    PubMed Central

    Psaltis, Peter J.

    2016-01-01

    Atherosclerosis is characterized by the formation of complex atheroma lesions (plaques) in arteries that pose risk by their flow-limiting nature and propensity for rupture and thrombotic occlusion. It develops in the context of disturbances to lipid metabolism and immune response, with inflammation underpinning all stages of plaque formation, progression and rupture. As the primary disease process responsible for myocardial infarction, stroke and peripheral vascular disease, atherosclerosis is a leading cause of morbidity and mortality on a global scale. A precise understanding of its pathogenic mechanisms is therefore critically important. Integral to this is the role of vascular wall imaging. Over recent years, the rapidly evolving field of molecular imaging has begun to revolutionize our ability to image beyond just the anatomical substrate of vascular disease, and more dynamically assess its pathobiology. Nuclear imaging by positron emission tomography (PET) can target specific molecular and biological pathways involved in atherosclerosis, with the application of 18Fluoride PET imaging being widely studied for its potential to identify plaques that are vulnerable or high risk. In this review, we discuss the emergence of 18Fluoride PET as a promising modality for the assessment of coronary atherosclerosis, focusing on the strengths and limitations of the two main radionuclide tracers that have been investigated to date: 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) and sodium 18F-fluoride (18F-NaF). PMID:27500093

  12. Ammonium Fluoride Mediated Synthesis of Anhydrous Metal Fluoride-Mesoporous Carbon Nanocomposites for High-Performance Lithium Ion Battery Cathodes.

    PubMed

    Chun, Jinyoung; Jo, Changshin; Sahgong, Sunhye; Kim, Min Gyu; Lim, Eunho; Kim, Dong Hyeon; Hwang, Jongkook; Kang, Eunae; Ryu, Keun Ah; Jung, Yoon Seok; Kim, Youngsik; Lee, Jinwoo

    2016-12-28

    Metal fluorides (MFx) are one of the most attractive cathode candidates for Li ion batteries (LIBs) due to their high conversion potentials with large capacities. However, only a limited number of synthetic methods, generally involving highly toxic or inaccessible reagents, currently exist, which has made it difficult to produce well-designed nanostructures suitable for cathodes; consequently, harnessing their potential cathodic properties has been a challenge. Herein, we report a new bottom-up synthetic method utilizing ammonium fluoride (NH4F) for the preparation of anhydrous MFx (CuF2, FeF3, and CoF2)/mesoporous carbon (MSU-F-C) nanocomposites, whereby a series of metal precursor nanoparticles preconfined in mesoporous carbon were readily converted to anhydrous MFx through simple heat treatment with NH4F under solventless conditions. We demonstrate the versatility, lower toxicity, and efficiency of this synthetic method and, using XRD analysis, propose a mechanism for the reaction. All MFx/MSU-F-C prepared in this study exhibited superior electrochemical performances, through conversion reactions, as the cathode for LIBs. In particular, FeF3/MSU-F-C maintained a capacity of 650 mAh g(-1)FeF3 across 50 cycles, which is ∼90% of its initial capacity. We expect that this facile synthesis method will trigger further research into the development of various nanostructured MFx for use in energy storage and other applications.

  13. Synthesis and Evaluation in Monkey of [18F]4-Fluoro-N-methyl-N-(4-(6- (methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide ([18F]FIMX), a Promising Radioligand for PET Imaging of Brain Metabotropic Glutamate Receptor 1 (mGluR1)

    PubMed Central

    Xu, Rong; Zanotti-Fregonara, Paolo; Zoghbi, Sami S.; Gladding, Robert L.; Woock, Alicia; Innis, Robert B.; Pike, Victor W

    2013-01-01

    We sought to develop a PET radioligand that would be useful for imaging human brain metabotropic subtype 1 receptors (mGluR1) in neuropsychiatric disorders and in drug development. 4-Fluoro-N-methyl-N-(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide (FIMX, 11) was identified as having favorable properties for development as a PET radioligand. We developed a method for preparing [18F]11 in useful radiochemical yield and in high specific activity from [18F]fluoride ion and an N-Boc-protected (phenyl)aryliodonium salt precursor (15). In baseline experiments in rhesus monkey, [18F]11 gave high brain radioactivity uptake reflecting the expected distribution of mGluR1 with notably high uptake in cerebellum which became 47% lower by 120 min after radioligand injection. Pharmacological challenges demonstrated a very high proportion of the radioactivity in monkey brain to be bound specifically and reversibly to mGluR1. [18F]11 is concluded to be an effective PET radioligand for imaging mGluR1 in monkey brain and therefore merits further evaluation in human subjects. PMID:24147864

  14. Automated synthesis of N-(2-[(18) F]Fluoropropionyl)-L-glutamic acid as an amino acid tracer for tumor imaging on a modified [(18) F]FDG synthesis module.

    PubMed

    Liu, Shaoyu; Sun, Aixia; Zhang, Zhanwen; Tang, Xiaolan; Nie, Dahong; Ma, Hui; Jiang, Shende; Tang, Ganghua

    2017-04-03

    N-(2-[(18) F]Fluoropropionyl)-L-glutamic acid ([(18) F]FPGLU) is a potential amino acid tracer for tumor imaging with positron emission tomography (PET). However, due to the complicated multi-step synthesis, the routine production of [(18) F]FPGLU presents many challenging laboratory requirements. In order to simplify the synthesis process of this interesting radiopharmaceutical, an efficient automated synthesis of [(18) F]FPGLU was performed on a modified commercial FDG synthesizer via a two-step on-column hydrolysis procedure, including (18) F-fluorination and on-column hydrolysis reaction. [(18) F]FPGLU was synthesized in 12 ± 2% (n = 10, uncorrected) radiochemical yield based on [(18) F]fluoride using the tosylated precursor 2. The radiochemical purity was ≥98%, and the overall synthesis time was 35 min. To further optimize the radiosynthesis conditions of [(18) F]FPGLU, a brominated precursor 3 was also used for the preparation of [(18) F]FPGLU and the improved radiochemical yield was up to 20 ± 3% (n = 10, uncorrected) in 35 min. Moreover, all these results were achieved using the similar on-column hydrolysis procedure on the modified FDG synthesis module.

  15. Oxidative aliphatic C-H fluorination with fluoride ion catalyzed by a manganese porphyrin.

    PubMed

    Liu, Wei; Huang, Xiongyi; Cheng, Mu-Jeng; Nielsen, Robert J; Goddard, William A; Groves, John T

    2012-09-14

    Despite the growing importance of fluorinated organic compounds in drug development, there are no direct protocols for the fluorination of aliphatic C-H bonds using conveniently handled fluoride salts. We have discovered that a manganese porphyrin complex catalyzes alkyl fluorination by fluoride ion under mild conditions in conjunction with stoichiometric oxidation by iodosylbenzene. Simple alkanes, terpenoids, and even steroids were selectively fluorinated at otherwise inaccessible sites in 50 to 60% yield. Decalin was fluorinated predominantly at the C2 and C3 methylene positions. Bornyl acetate was converted to exo-5-fluoro-bornyl acetate, and 5α-androstan-17-one was fluorinated selectively in the A ring. Mechanistic analysis suggests that the regioselectivity for C-H bond cleavage is directed by an oxomanganese(V) catalytic intermediate followed by F delivery via an unusual manganese(IV) fluoride that has been isolated and structurally characterized.

  16. Fluoride antireflection coatings for deep ultraviolet optics deposited by ion-beam sputtering.

    PubMed

    Yoshida, Toshiya; Nishimoto, Keiji; Sekine, Keiichi; Etoh, Kazuyuki

    2006-03-01

    Optically high quality coatings of fluoride materials are required in deep ultraviolet (DUV) lithography. We have applied ion-beam sputtering (IBS) to obtain fluoride films with smooth surfaces. The extinction coefficients were of the order of 10(-4) at the wavelength of 193 nm due to the reduction of their absorption loss. The transmittance of the MgF2/GdF3 antireflection coating was as high as 99.7% at the wavelength of 193 nm. The surfaces of the IBS deposited films were so smooth that the surface roughness of the A1F3/GdF3 film was comparable with that of the CaF2 substrate. The MgF2/GdF3 coating fulfilled the temperature and humidity requirements of military specification. Thus, the IBS deposited fluoride films are promising candidate for use in the DUV lithography optics.

  17. Ion spatial distributions at the liquid-vapor interface of aqueous potassium fluoride solutions

    SciTech Connect

    Brown, M A; D'Auria, R; Kuo, I W; Krisch, M J; Starr, D E; Bluhm, H; Tobias, D J; Hemminger, J C

    2008-04-23

    X-ray photoemission spectroscopy operating under ambient pressure conditions is used to probe ion distributions throughout the interfacial region of a free-flowing aqueous liquid micro-jet of 6 M potassium fluoride. Varying the energy of the ejected photoelectrons by carrying out experiments as a function of x-ray wavelength measures the composition of the aqueous-vapor interfacial region at various depths. The F{sup -} to K{sup +} atomic ratio is equal to unity throughout the interfacial region to a depth of 2 nm. The experimental ion profiles are compared with the results of a classical molecular dynamics simulation of a 6 M aqueous KF solution employing polarizable potentials. The experimental results are in qualitative agreement with the simulations when integrated over an exponentially decaying probe depth characteristic of an APPES experiment. First principles molecular dynamics simulations have been used to calculate the potential of mean force for moving a fluoride anion across the air-water interface. The results show that the fluoride anion is repelled from the interface, and this is consistent with the depletion of F{sup -} at the interface revealed by the APPES experiment and polarizable force field-based molecular dynamics simulation. Together, the APPES and MD simulation data provide a detailed description of the aqueous-vapor interface of alkali fluoride systems. This work offers the first direct observation of the ion distribution at a potassium fluoride aqueous solution interface. The current experimental results are compared to those previously obtained for saturated solutions of KBr and KI to underscore the strong difference in surface propensity between soft/large and hard/small halide ions in aqueous solution.

  18. Ion spatial distributions at the liquid-vapor interface of aqueous potassium fluoride solutions.

    PubMed

    Brown, Matthew A; D'Auria, Raffaella; Kuo, I-F William; Krisch, Maria J; Starr, David E; Bluhm, Hendrik; Tobias, Douglas J; Hemminger, John C

    2008-08-28

    X-Ray photoemission spectroscopy operating under ambient pressure conditions is used to probe ion distributions throughout the interfacial region of a free-flowing aqueous liquid micro-jet of 6 M potassium fluoride. Varying the energy of the ejected photoelectrons by carrying out experiments as a function of X-ray wavelength measures the composition of the aqueous-vapor interfacial region at various depths. The F(-) to K(+) atomic ratio is equal to unity throughout the interfacial region to a depth of 2 nm. The experimental ion profiles are compared with the results of a classical molecular dynamics simulation of a 6 M aqueous KF solution employing polarizable potentials. The experimental results are in qualitative agreement with the simulations when integrated over an exponentially decaying probe depth characteristic of an APPES experiment. First principles molecular dynamics simulations have been used to calculate the potential of mean force for moving a fluoride anion across the air-water interface. The results show that the fluoride anion is repelled from the interface, consistent with the depletion of F(-) at the interface revealed by the APPES experiment and polarizable force field-based molecular dynamics simulation. Together, the APPES and MD simulation data provide a detailed description of the aqueous-vapor interface of alkali fluoride systems. This work offers the first direct observation of the ion distribution at an aqueous potassium fluoride solution interface. The current experimental results are compared to those previously obtained for saturated solutions of KBr and KI to underscore the strong difference in surface propensity between soft/large and hard/small halide ions in aqueous solution.

  19. Ab initio calculations on the positive ions of the alkaline-earth oxides, fluorides, and hydroxides

    NASA Technical Reports Server (NTRS)

    Partridge, H.; Langhoff, S. R.; Bauschlicher, C. W., Jr.

    1986-01-01

    Theoretical dissociation energies are presented for the alkaline-earth fluoride, hydroxide, and oxide positive ions that are considered to be accurate to 0.1-0.2 eV. The r(e) for the positive ions are found to be consistently shorter than the corresponding neutrals by 0.07 + or -0.02 A. The bonding in the ground states is demonstrated to be of predominantly M + 2 X - character. The a 3 Pi and A 1 Pi are found to lie considerably above the X 1 Sigma + ground states of the alkaline-earth fluoride and hydroxide positive ions. The overall agreement of the theoretical ionization potentials with the available experimental appearance potentials is satisfactory; these values should represent the most accurate and consistent set available.

  20. PRECIPITATION OF ZIRCONIUM AND FLUORIDE IONS FROM SOLUTIONS

    DOEpatents

    Newby, B.J.

    1963-06-11

    A process is given for removing zirconium and fluorine ions from aqueous solutions also containing uranium(VI). The precipitation is carried out with sodium formate, and the uranium remains in solution. (AEC)

  1. Capillary electrophoresis with contactless conductivity detection for the quantification of fluoride in lithium ion battery electrolytes and in ionic liquids-A comparison to the results gained with a fluoride ion-selective electrode.

    PubMed

    Pyschik, Marcelina; Klein-Hitpaß, Marcel; Girod, Sabrina; Winter, Martin; Nowak, Sascha

    2017-02-01

    In this study, an optimized method using capillary electrophoresis (CE) with a direct contactless conductivity detector (C(4) D) for a new application field is presented for the quantification of fluoride in common used lithium ion battery (LIB) electrolyte using LiPF6 in organic carbonate solvents and in ionic liquids (ILs) after contacted to Li metal. The method development for finding the right buffer and the suitable CE conditions for the quantification of fluoride was investigated. The results of the concentration of fluoride in different LIB electrolyte samples were compared to the results from the ion-selective electrode (ISE). The relative standard deviations (RSDs) and recovery rates for fluoride were obtained with a very high accuracy in both methods. The results of the fluoride concentration in the LIB electrolytes were in very good agreement for both methods. In addition, the limit of detection (LOD) and limit of quantification (LOQ) values were determined for the CE method. The CE method has been applied also for the quantification of fluoride in ILs. In the fresh IL sample, the concentration of fluoride was under the LOD. Another sample of the IL mixed with Li metal has been investigated as well. It was possible to quantify the fluoride concentration in this sample.

  2. A comparison of (/sup 18/F)spiroperidol, (/sup 18/F)benperidol and (/sup 18/F) haloperidol kinetics in baboon brain

    SciTech Connect

    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/..mu..mol. 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 (approx. =0.07% per ml vs. approx. = 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 approx. = 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.

  3. The influence of fluoride ions on the equilibrium between titanium ions and titanium metal in fused alkali chloride melts.

    PubMed

    Song, Jianxun; Wang, Qiuyu; Wu, Jinyu; Jiao, Shuqiang; Zhu, Hongmin

    2016-08-15

    KF is employed as a source of fluoride ions added to the melt to disclose the influence of fluoride on the disproportionation reactions of titanium ions, 3Ti(2+) = 2Ti(3+) + Ti, and 4Ti(3+) = 3Ti(4+) + Ti. The results reveal that the equilibrium transferred to the right direction for the first reaction and the apparent equilibrium constant increased sharply, mainly because of the formation of coordination compounds: TiFi(3-i). The accurate values of the equilibrium constants referring to the formation reactions of Ti(3+) + iF(-) = TiFi(3-i) (i = 1-6) in NaCl-KCl melt at 1023 K were evaluated with a best fit least squares method. It is also revealed that the stable states of the coordination compounds are TiF(2+), TiF2(+), TiF4(-) and TiF6(3-). Moreover, the Gibbs free energies for complex formation were estimated. Ti(2+) was undetectable when the concentration of fluoride ion was high enough. The equilibrium constant for the formation reaction, Ti(4-) + 6F(-) = TiF6(2-), was evaluated. The equilibrium constant, Kc2, for the disproportionation reaction 4Ti(3+) = 3Ti(4+) + Ti, in chloride melt was determined as 0.015.

  4. Gas-phase energetics of thorium fluorides and their ions.

    PubMed

    Irikura, Karl K

    2013-02-14

    Gas-phase thermochemistry for neutral ThF(n) and cations ThF(n)(+) (n = 1-4) is obtained from large-basis CCSD(T) calculations, with a small-core pseudopotential on thorium. Electronic partition functions are computed with the help of relativistic MRCI calculations. Geometries, vibrational spectra, electronic fine structure, and ion appearance energies are tabulated. These results support the experimental results by Lau, Brittain, and Hildenbrand for the neutral species, except for ThF. The ion thermochemistry is presented here for the first time.

  5. An estimation of safe concentrations of fluoride ion for rainbow trout and brown trout

    SciTech Connect

    Camargo, J.A.

    1995-12-31

    Safe concentrations of fluoride ion (F-) for two trout species, Oncorhynchus mykiss Walbaum and Salmo trutta L., were estimated from short-term toxicity bioassays (maximum exposure time of 192 hours) using the multifactor probit analysis (MPA) software on lethal data. The MPA software solves the concentration-time-response equation simultaneously via the iterative reweighed least squares technique (multiple linear regression). A safe concentration (SC) refers to the concentration of toxic substance that can exist in a laboratory environment for an extended exposure time (infinite hours) causing mortality at 0.01% population of test species. Toxicity bioassays were conducted in soft water (average hardness value of 21.8 mg CaCO{sub 3}/L). Test fluoride solutions were made from sodium fluoride (NaF). There was a differential response to fluoride toxicity between test species, O. mykiss appearing to be a more sensitive species. SC values (mg F-/L) and their 95% confidence limits were 5.14 (3.10--7.53) for O. mykiss and 7.49 (4.42--10.96) for S. trutta. These SCs are higher than safe concentrations proposed for freshwater invertebrates. It is concluded that the combination of acute toxicity testing and MPA software may be a valuable methodology in environmental toxicology to estimate accurate safe concentrations of chemical compounds for aquatic organisms. However, this methodology should not be viewed as a perfect alternative to chronic toxicity testing.

  6. Compartmental model of 18F-choline

    NASA Astrophysics Data System (ADS)

    Janzen, T.; Tavola, F.; Giussani, A.; Cantone, M. C.; Uusijärvi, H.; Mattsson, S.; Zankl, M.; Petoussi-Henß, N.; Hoeschen, C.

    2010-03-01

    The MADEIRA Project (Minimizing Activity and Dose with Enhanced Image quality by Radiopharmaceutical Administrations), aims to improve the efficacy and safety of 3D functional imaging by optimizing, among others, the knowledge of the temporal variation of the radiopharmaceuticals' uptake in and clearance from tumor and healthy tissues. With the help of compartmental modeling it is intended to optimize the time schedule for data collection and improve the evaluation of the organ doses to the patients. Administration of 18F-choline to screen for recurrence or the occurrence of metastases in prostate cancer patients is one of the diagnostic applications under consideration in the frame of the project. PET and CT images have been acquired up to four hours after injection of 18F-choline. Additionally blood and urine samples have been collected and measured in a gamma counter. The radioactivity concentration in different organs and data of plasma clearance and elimination into urine were used to set-up a compartmental model of the biokinetics of the radiopharmaceutical. It features a central compartment (blood) exchanging with organs. The structure describes explicitly liver, kidneys, spleen, plasma and bladder as separate units with a forcing function approach. The model is presented together with an evaluation of the individual and population kinetic parameters, and a revised time schedule for data collection is proposed. This optimized time schedule will be validated in a further set of patient studies.

  7. Ratiometric fluorescent chemosensor for fluoride ion based on inhibition of excited state intramolecular proton transfer

    NASA Astrophysics Data System (ADS)

    Gupta, Akul Sen; Paul, Kamaldeep; Luxami, Vijay

    2015-03-01

    ESIPT based benzimidazole derivative has been synthesized and investigated their photophysical behavior towards various anions. The probe 2 has been used for selective estimation of F- ions as compared to other anions and signaled the binding event through formation of new absorption band at 360 nm and emission band at 420 nm. The probe 2 showed fluorescence behavior towards fluoride ions through hydrogen bonding interactions and restricted the ESIPT emission at 540 nm from OH to nitrogen of benzimidazole moiety to release its enol emission at 420 nm.

  8. Dentifrice Fluoride

    NASA Astrophysics Data System (ADS)

    Rakita, Philip E.

    2004-05-01

    The effectiveness of the fluoride ion in lowering the incidence of dental caries is a major factor in the field of dental health. Observations and research studies in the first half of the 20th century have lead to the widespread adoption of fluoridated water and the use of inorganic fluoride compounds in oral care products, such as toothpaste and dental rinses. This article provides a brief review of the types of compounds used and the chemistry involved.

  9. A Practical, Automated Synthesis of meta-[18F]Fluorobenzylguanidine for Clinical Use

    PubMed Central

    Hu, Bao; Vāvere, Amy L.; Neumann, Kiel D.; Shulkin, Barry L.; DiMagno, Stephen G.; Snyder, Scott E.

    2015-01-01

    Many neuroendocrine tumors, such as neuroblastoma (NB), arise from neural crest cells of the sympathetic nervous system. This nerve-like phenotype has been exploited for functional imaging using radioactive probes originally designed for neuronal and adrenal medullary applications. NB imaging with meta-[123I]iodobenzylguanidine ([123I]MIBG) is limited by the emissions of 123I, which lead to poor image resolution and challenges in quantification of its accumulation in tumors. Meta-[18F]Fluorobenzylguanidine ([18F]MFBG) is a promising alternative to [123I]MIBG that could change the standard of practice for imaging neuroendocrine tumors, but interest in this PET radiotracer has suffered due to its complex and inefficient radiosynthesis. Here we report a two-step, automated method for the routine production of [18F]MFBG by thermolysis of a diaryliodonium fluoride and subsequent acid deprotection. The synthesis was adapted for use on a commercially available synthesizer for routine production. Full characterization of [18F]MFBG produced by this route demonstrated the tracer’s suitability for human use. [18F]MFBG was prepared in almost three-fold higher yield than previously reported (31% corrected to end of bombardment, n = 9) in a synthesis time of 56 minutes with > 99.9% radiochemical purity. Other than pH adjustment and dilution of the final product, no reformulation was necessary after purification. This method permits the automated production of multidose batches of clinical grade [18F]MFBG. Moreover, if ongoing clinical imaging trials of [18F]MFBG are successful, this methodology is suitable for rapid commercialization and can be easily adapted for use on most commercial automated radiosynthesis equipment. PMID:26313342

  10. Automated Synthesis of 18F Analogue of Paclitaxel (PAC): [18F]Paclitaxel (FPAC)

    PubMed Central

    Kalen, Joseph D.; Hirsch, Jerry I.; Kurdziel, Karen A.; Eckelman, William C.; Kiesewetter, Dale O.

    2007-01-01

    A positron-emitting paclitaxel (PAC) derivative could allow in-vivo measurement of multidrug resistance in tumors and, therefore, predict a potential chemotherapeutic benefit to patients. [18F]Paclitaxel was produced using a 2-reaction vessel automated synthesizer followed by HPLC purification. Optimized reaction conditions resulted in radiochemical yields of 21.2 ± 9.6% at end of bombardment, radiochemical purity > 99%, and specific activity of 159 ± 43 GBq/μmol. [18F]Paclitaxel activities of 1.33 ± 0.729 GBq (n=7) were obtained in sterile, pyrogen-free solution for IV administration. PMID:17161952

  11. Synthesis of 6-acrylamido-4-(2-[18F]fluoroanilino)quinazoline: Aprospective irreversible EGFR binding probe

    SciTech Connect

    Vasdev, Neil; Dorff, Peter N.; Gibbs, Andrew R.; Nandanan,Erathodiyil; Reid, Leanne M.; O'Neil, James P.; VanBrocklin, Henry F.

    2004-03-30

    Acrylamido-quinazolines substituted at the 6-position bindirreversibly to the intracellular ATP binding domain of the epidermalgrowth factor receptor (EGFR). A general route was developed forpreparing 6-substituted-4-anilinoquinazolines from [18F]fluoroanilinesfor evaluation as EGFR targeting agents with PET. By a cyclizationreaction, 2-[18F]fluoroaniline was reacted withN'-(2-cyano-4-nitrophenyl)-N,N-dimethylimidoformamide to produce6-nitro-4-(2-[18F]fluoroanilino)quinazoline in 27.5 percentdecay-corrected radiochemical yield. Acid mediated tin chloride reductionof the nitro group was achieved in 5 min (80 percent conversion) andsubsequent acylation with acrylic acid gave6-acrylamido-4-(2-[18F]fluoroanilino)quinazoline in 8.5 percentdecay-corrected radiochemical yield, from starting fluoride, in less than2 hours.

  12. Tuning the Colors of the Dark Isomers of Photochromic Boron Compounds with Fluoride Ions: Four-State Color Switching.

    PubMed

    Mellerup, Soren K; Rao, Ying-Li; Amarne, Hazem; Wang, Suning

    2016-09-02

    Combining a three-coordinated boron (BMes2) moiety with a four-coordinated photochromic organoboron unit leads to a series of new diboron compounds that undergo four-state reversible color switching in response to stimuli of light, heat, and fluoride ions. Thus, these hybrid diboron systems allow both convenient color tuning/switching of such photochromic systems, as well as visual fluoride sensing by color or fluorescent emission color change.

  13. A one-step automated synthesis of the dopamine transporter ligand [(18)F]FECNT from the chlorinated precursor.

    PubMed

    Pijarowska-Kruszyna, Justyna; Jaron, Antoni; Kachniarz, Artur; Malkowski, Bogdan; Garnuszek, Piotr; Mikolajczak, Renata

    2016-03-01

    The use of [(18)F]labelled nortropane derivative 2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)-nortropane (FECNT) as a dopamine transporter ligand for PET imaging is dependent on efficient radiosynthesis method. Herein, the automated synthesis of [(18)F]FECNT from its chlorinated precursor in commercially available SynChrom [(18)F] R&D module has been developed. The synthesis unit was readily configured for the one-step synthesis from corresponding chlorinated precursor. The radiolabeling process involved a classical [(18)F]fluoride nucleophilic substitution performed at 110 °C for 12 min and finally HPLC and SPE purification. Crude [(18)F]FECNT was obtained with a radiolabeling yield of 59 ± 12% (n = 5). The average uncorrected amount of [(18)F]FECNT in the final formulated dose was 2.0 ± 0.5 GBq (32 ± 7% overall decay-corrected yields) obtained with radiochemical purity over 99% and specific activity of 55 GBq/µmol. The total duration of the procedure was 80-90 min. An automated radiosynthesis of [(18)F]FECNT with high radiochemical purity may provide a simple and robust method of radiopharmaceutical preparation for routine clinical applications.

  14. Oxidative aliphatic C-H fluorination with manganese catalysts and fluoride ion

    PubMed Central

    Liu, Wei; Huang, Xiongyi; Groves, John T

    2014-01-01

    Fluorination is a reaction that is useful in improving the chemical stability and changing the binding affinity of biologically active compounds. The protocol described here can be used to replace aliphatic, C(sp3)-H hydrogen in small molecules with fluorine. Notably, isolated methylene groups and unactivated benzylic sites are accessible. The method uses readily available manganese porphyrin and manganese salen catalysts and various fluoride ion reagents, including silver fluoride (AgF), tetrabutylammonium fluoride and triethylamine trihydrofluoride (TREAT·HF), as the source of fluorine. Typically, the reactions afford 50–70% yield of mono-fluorinated products in one step. Two representative examples, the fragrance component celestolide and the nonsteroidal anti-inflammatory drug ibuprofen, are described; they produced useful isolated quantities (250–300 mg, ~50% yield) of fluorinated material over periods of 1–8 h. The procedures are performed in a typical fume hood using ordinary laboratory glassware. No special precautions to rigorously exclude water are required. PMID:24177292

  15. Determination of Fluoride in Toothpaste Using an Ion-Selective Electrode

    ERIC Educational Resources Information Center

    Light, Truman S.; Cappuccino, Carleton C.

    1975-01-01

    Outlines the theory of chemical potentiometry, describes the experimental procedure for free fluoride determination, and presents sample data of fluoride concentration for various brands of toothpaste. (GS)

  16. Molten fluoride salts incorporation into pristine and ion-modified carbon allotropes and metallic foils

    NASA Astrophysics Data System (ADS)

    Vacík, J.; Hnatowicz, V.; Ĉervená, J.; Mach, R.; Peka, I.

    1999-01-01

    Incorporation of molten fluoride salts into different carbon allotropes (glassy carbon, pyrolytic graphite etc.) and metallic foils (Ni, Ti, etc.), pristine and ion- treated substances, has been studied using non-destructive, depth sensitive nuclear analytical methods—Neutron Depth Profiling (NDP) and Rutherford Backscattering (RBS). Strong interaction between the molten LiF and LiF+KF+NaF salts and the tested materials was found. The results are of great interest for accelerator driven transmutation technology (ADTT) which is a promising way towards effective liquidation of nuclear wastes.

  17. Characterization of Physiologic (18)F FSPG Uptake in Healthy Volunteers.

    PubMed

    Mosci, Camila; Kumar, Meena; Smolarz, Kamilla; Koglin, Norman; Stephens, Andrew W; Schwaiger, Markus; Gambhir, Sanjiv S; Mittra, Erik S

    2016-06-01

    Purpose To evaluate the normal biodistribution and kinetics of (S)-4-(3-[18F]fluoropropyl)-l-glutamic acid ((18)F FSPG) in healthy volunteers and to compare (18)F FSPG mean and maximum standardized uptake values (SUVmean and SUVmax, respectively) with those of (18)F fluorodeoxyglucose (FDG) across a variety of organs. Materials and Methods This protocol was reviewed and approved by all appropriate regulatory authorities. An 8-mCi (±10%) dose of (18)F FSPG was given to five subjects (three women, two men), and seven whole-body positron emission tomography (PET) scans were performed 5, 10, 20, 30, 45, 150, and 240 minutes after injection. Regions of interest were analyzed on the resultant (18)F FSPG images to evaluate the kinetics of this radiotracer. The images obtained 45 minutes after injection were used to measure SUVmean and SUVmax in additional regions of the body. These values were compared with similar values obtained with (18)F FDG PET published previously. Descriptive statistics, including average and standard deviation across the five subjects, were used. (18)F FSPG SUVmean and SUVmax were compared. Results On the (18)F FSPG images obtained 45 minutes after injection, there was only low-grade background activity in the majority of analyzed regions. Prominent activity was seen throughout the pancreas. Clearance of the radiotracer through the kidneys and collection in the bladder also were seen. SUV quantification shows notable differences between (18)F FSPG and (18)F FDG in the pancreas ((18)F FSPG SUVmean, 8.2; (18)F FDG SUVmean, 1.3), stomach ((18)F FSPG SUVmax, 3.6; (18)F FDG SUVmax, 1.6), and brain ((18)F FSPG SUVmean, 0.08; (18)F FDG SUVmean, 7.8). The kinetic data showed rapid clearance of the radiotracer from the blood pool and most organs, except the pancreas. Conclusion (18)F FSPG is a PET radiopharmaceutical characterized by rapid clearance from most healthy tissues, except the pancreas and kidneys. A consistent biodistribution pattern was

  18. Stabilization of Th{sup 3+} ions into mixed-valence thorium fluoride

    SciTech Connect

    Dubois, Marc; Dieudonne, Belto; Mesbah, Adel; Bonnet, Pierre; El-Ghozzi, Malika; Renaudin, Guillaume; Avignant, Daniel

    2011-01-15

    The unusual oxidation state +3 of the thorium has been stabilized into a lithium containing non-stoichiometric mixed-valence (III/IV) thorium fluorinated phase with formula Li{sub 2+x}Th{sub 12}F{sub 50} (0ions can be divided into two groups and are located either in locked positions or in open channels of the three dimensional framework. The amount of Li{sup +} ions in open channels can be variable, so that the afore mentioned single phase may be considered as an insertion compound. The Li{sup +} insertion is accompanied by the simultaneous reduction of a part of the Th{sup 4+} ions, resulting in a mixed-valence III/IV thorium fluoride. The electrochemical insertion of Li{sup +} ions into the open channels of the host matrix has been carried out at 60 {sup o}C, using an alkylcarbonate PC-LiClO{sub 4} 1 M electrolyte. The Li{sup +} and Th{sup 3+} contents, both in the starting composition and the Li{sup +} inserted ones, were investigated by high resolution solid state {sup 7}Li NMR and EPR, respectively. -- Graphical abstract: Electrochemical insertion of Li{sup +} ions into mixed-valence III/IV thorium fluoride and EPR spectra for the raw and inserted compounds. Display Omitted

  19. NIR to VUV: Seven-Photon Upconversion Emissions from Gd(3+) Ions in Fluoride Nanocrystals.

    PubMed

    Zheng, Kezhi; Qin, Weiping; Cao, Chunyan; Zhao, Dan; Wang, Lili

    2015-02-05

    Here we show that a near-infrared (NIR) diode laser is capable of generating vacuum ultraviolet (VUV) emissions in fluoride nanocrystals through photon upconversion (UC) processes. By using Yb(3+) and Tm(3+) as sensitizers, we successfully obtained the VUV photons with the energy exceeding 6 eV in YF3: Yb, Tm, and Gd nanocrystals. The seven photon UC fluorescence from the (6)GJ → (8)S7/2 transitions of Gd(3+) ions and the possible VUV UC mechanism were reported along with the calculation of the branching ratio under different pumping power excitation. Practically, it offers a promising solution for VUV light generation without cryogens and expensive instrumentations. Fundamentally, the extremely high-order UC processes will intrigue great interest in exploring unusual high-energy radiative transitions in rare earth ions.

  20. A family of fluoride-specific ion channels with dual-topology architecture

    PubMed Central

    Stockbridge, Randy B; Robertson, Janice L; Kolmakova-Partensky, Ludmila; Miller, Christopher

    2013-01-01

    Fluoride ion, ubiquitous in soil, water, and marine environments, is a chronic threat to microorganisms. Many prokaryotes, archea, unicellular eukaryotes, and plants use a recently discovered family of F− exporter proteins to lower cytoplasmic F− levels to counteract the anion’s toxicity. We show here that these ‘Fluc’ proteins, purified and reconstituted in liposomes and planar phospholipid bilayers, form constitutively open anion channels with extreme selectivity for F− over Cl−. The active channel is a dimer of identical or homologous subunits arranged in antiparallel transmembrane orientation. This dual-topology assembly has not previously been seen in ion channels but is known in multidrug transporters of the SMR family, and is suggestive of an evolutionary antecedent of the inverted repeats found within the subunits of many membrane transport proteins. DOI: http://dx.doi.org/10.7554/eLife.01084.001 PMID:23991286

  1. Polyethylene-supported polyvinylidene fluoride-cellulose acetate butyrate blended polymer electrolyte for lithium ion battery

    NASA Astrophysics Data System (ADS)

    Liu, Jiansheng; Li, Weishan; Zuo, Xiaoxi; Liu, Shengqi; Li, Zhao

    2013-03-01

    The polyethylene (PE)-supported polymer membranes based on the blended polyvinylidene fluoride (PVDF) and cellulose acetate butyrate (CAB) are prepared for gel polymer electrolyte (GPE) of lithium ion battery. The performances of the prepared membranes and the resulting GPEs are investigated by scanning electron microscopy, electrochemical impedance spectroscopy, linear potential sweep, and charge-discharge test. The effect of the ratio of PVDF to CAB on the performance of the prepared membranes is considered. It is found that the GPE based on the blended polymer with PVDF:CAB = 2:1 (in weight) has the largest ionic conductivity (2.48 × 10-3 S cm-1) and shows good compatibility with anode and cathode of lithium ion battery. The LiCoO2/graphite battery using this GPE exhibits superior cyclic stability at room temperature, storage performance at elevated temperature, and rate performance.

  2. 18F-FET and 18F-FCH uptake in human glioblastoma T98G cell lines

    PubMed Central

    Persico, Marco Giovanni; Buroni, Federica Eleonora; Pasi, Francesca; Aprile, Carlo; Nano, Rosanna; Hodolic, Marina

    2016-01-01

    Abstract Background Despite complex treatment of surgery, radiotherapy and chemotherapy, high grade gliomas often recur. Differentiation between post-treatment changes and recurrence is difficult. 18F-methyl-choline (18F-FCH) is frequently used in staging and detection of recurrent prostate cancer disease as well as some brain tumours; however accumulation in inflammatory tissue limits its specificity. The 18F-ethyl-tyrosine (18F-FET) shows a specific uptake in malignant cells, resulting from increased expression of amino acid transporters or diffusing through the disrupted blood-brain barrier. 18F-FET exhibits lower uptake in machrophages and other inflammatory cells. Aim of this study was to evaluate 18F-FCH and 18F-FET uptake by human glioblastoma T98G cells. Material and methods Human glioblastoma T98G or human dermal fibroblasts cells, seeded at a density to obtain 2 × 105 cells per flask when radioactive tracers were administered, grew adherent to the plastic surface at 37°C in 5% CO2 in complete medium. Equimolar amounts of radiopharmaceuticals were added to cells for different incubation times (20 to 120 minutes) for 18F-FCH and 18F-FET respectively. The cellular radiotracer uptake was determined with a gamma counter. All experiments were carried out in duplicate and repeated three times. The uptake measurements are expressed as the percentage of the administered dose of tracer per 2 × 105 cells. Data (expressed as mean values of % uptake of radiopharmaceuticals) were compared using parametric or non-parametric tests as appropriate. Differences were regarded as statistically significant when p<0.05. Results A significant uptake of 18F-FCH was seen in T98G cells at 60, 90 and 120 minutes. The percentage uptake of 18F-FET in comparison to 18F-FCH was lower by a factor of more than 3, with different kinetic curves.18F-FET showed a more rapid initial uptake up to 40 minutes and 18F-FCH showed a progressive rise reaching a maximum after 90 minutes

  3. cGMP Production of the Radiopharmaceutical [(18) F]MK-6240 for PET imaging of Human Neurofibrillary Tangles.

    PubMed

    Collier, Thomas Lee; Yokell, Daniel L; Livni, Eli; Rice, Peter A; Celen, Sofie; Serdons, Kim; Neelamegam, Ramesh; Bormans, Guy; Harris, Dawn; Walji, Abbas; Hostetler, Eric D; Bennacef, Idriss; Vasdev, Neil

    2017-02-09

    Fluorine-18 labelled 6-(fluoro)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([(18) F]MK-6240) is a novel potent and selective PET radiopharmaceutical for detecting human neurofibrillary tangles, which are made up of aggregated tau protein. Herein, we report the fully automated two-step radiosynthesis of [(18) F]MK-6240 using a commercially available radiosynthesis module, GE Healthcare Tracerlab(TM) FXFN . Nucleophilic fluorination of the 5-diBoc-6-nitro precursor with potassium cryptand [(18) F]fluoride (K[(18) F]/K222 ) was carried out by conventional heating, followed by acid deprotection and semi-preparative HPLC under isocratic conditions. The isolated product was diluted with formulation solution and sterile filtered under Current Good Manufacturing Practices (cGMPs), and quality control procedures were established to validate this radiopharmaceutical for human use. At the end of synthesis, 6.3 - 9.3 GBq (170 - 250 mCi) of [(18) F]MK-6240 was formulated and ready for injection, in an uncorrected radiochemical yield of 7.5 ± 1.9% (relative to starting [(18) F]fluoride) with a specific activity of 222 ± 67 GBq/µmol (6.0 ± 1.8 Ci/µmol) at the end of synthesis (90 min; n = 3). [(18) F]MK-6240 was successfully validated for human PET studies meeting all FDA and USP requirements for a PET radiopharmaceutical. The present method can be easily adopted for use with other radiofluorination modules for widespread clinical research use.

  4. Fluoride absorption: independence from plasma fluoride levels

    SciTech Connect

    Whitford, G.M.; Williams, J.L.

    1986-04-01

    The concept that there are physiologic mechanisms to homeostatically regulate plasma fluoride concentrations has been supported by results in the literature suggesting an inverse relationship between plasma fluoride levels and the absorption of the ion from the gastrointestinal tract of the rat. The validity of the relationship was questioned because of possible problems in the experimental design. The present work used four different methods to evaluate the effect of plasma fluoride levels on the absorption of the ion in rats: (i) the percentage of the daily fluoride intake that was excreted in the urine; (ii) the concentration of fluoride in femur epiphyses; (iii) the net areas under the time-plasma fluoride concentration curves after intragastric fluoride doses; and (iv) the residual amounts or fluoride in the gastrointestinal tracts after the intragastric fluoride doses. None of these methods indicated that plasma fluoride levels influence the rate or the degree or fluoride absorption. It was concluded that, unless extremely high plasma fluoride levels are involved (pharmacologic or toxic doses), the absorption of the ion is independent of plasma levels. The results provide further evidence that plasma fluoride concentrations are not homeostatically regulated.

  5. Ion-selective electrode in determining fluorine in binary fluorides of metals of groups II-V

    SciTech Connect

    Mishchenko, V.T.; Mukomel', V.L.; Polvektov, N.S.; Shilova, L.P.; Tselik, E.I.

    1986-01-01

    The authors have developed a method of determining fluorine by ion-selective electrode techniques in specimens containing mixtures of the fluorides of magnesium and the rare-earth elements (REE), as well as scandium and bismuth. The specimens after treatment at high temperatures are sparingly soluble at room temperature in water and also in aqueous solutions of acids and bases. The authors found that a mixture of KNaCO/sub 3/ and K/sub 2/S/sub 2/O/sub 8/ with a mass ratio of 2:1 was an effective flux for MgF/sub 2/-MeF/sub 3/ specimens, where Me is an REE ion. The combined method of analyzing binary mixtures of fluorides (Mg and REE, Sc and Bi) which provides satisfactory accuracy and reliability in determining the fluoride and two different metals whose compounds may have various ratios in the samples.

  6. Energy transfer kinetics in oxy-fluoride glass and glass-ceramics doped with rare-earth ions

    SciTech Connect

    Sontakke, Atul D.; Annapurna, K.

    2012-07-01

    An investigation of donor-acceptor energy transfer kinetics in dual rare earths doped precursor oxy-fluoride glass and its glass-ceramics containing NaYF{sub 4} nano-crystals is reported here, using three different donor-acceptor ion combinations such as Nd-Yb, Yb-Dy, and Nd-Dy. The precipitation of NaYF{sub 4} nano-crystals in host glass matrix under controlled post heat treatment of precursor oxy-fluoride glasses has been confirmed from XRD, FESEM, and transmission electron microscope (TEM) analysis. Further, the incorporation of dopant ions inside fluoride nano-crystals has been established through optical absorption and TEM-EDX analysis. The noticed decreasing trend in donor to acceptor energy transfer efficiency from precursor glass to glass-ceramics in all three combinations have been explained based on the structural rearrangements that occurred during the heat treatment process. The reduced coupling phonon energy for the dopant ions due to fluoride environment and its influence on the overall phonon assisted contribution in energy transfer process has been illustrated. Additionally, realization of a correlated distribution of dopant ions causing clustering inside nano-crystals has also been reported.

  7. A novel fast ion chromatographic method for the analysis of fluoride in Antarctic snow and ice.

    PubMed

    Severi, Mirko; Becagli, Silvia; Frosini, Daniele; Marconi, Miriam; Traversi, Rita; Udisti, Roberto

    2014-01-01

    Ice cores are widely used to reconstruct past changes of the climate system. For instance, the ice core record of numerous water-soluble and insoluble chemical species that are trapped in snow and ice offer the possibility to investigate past changes of various key compounds present in the atmosphere (i.e., aerosol, reactive gases). We developed a new method for the quantitative determination of fluoride in ice cores at sub-μg L(-1) levels by coupling a flow injection analysis technique with a fast ion chromatography separation based on the "heart cut" column switching technology. Sensitivity, linear range (up to 60 μg L(-1)), reproducibility, and detection limit (0.02 μg L(-1)) were evaluated for the new method. This method was successfully applied to the analysis of fluoride at trace levels in more than 450 recent snow samples collected during the 1998-1999 International Trans-Antarctica Scientific Expedition traverse in East Antarctica at sites located between 170 and 850 km from the coastline.

  8. Displacement of the proton in hydrogen-bonded complexes of hydrogen fluoride by beryllium and magnesium ions

    SciTech Connect

    McDowell, Sean A. C.

    2009-05-14

    The displacement of the proton by a beryllium ion and by a magnesium ion from hydrogen-bonded complexes of hydrogen fluoride, of varying hydrogen bond strengths, was investigated theoretically using ab initio methods. Stable metal-containing species were obtained from all of the hydrogen-bonded complexes regardless of the strength of the hydrogen bond. It was found that the beryllium ion was energetically very effective in displacing the proton from hydrogen bonds, whereas the magnesium ion was unable to do so. The high stability of the beryllium-containing complexes is mainly due to the strong electrostatic bonding between the beryllium and fluoride atoms. This work supports the recent finding from a multidisciplinary bioinorganic study that beryllium displaces the proton in many strong hydrogen bonds.

  9. Comparative Analysis between [(18)F]Fludarabine-PET and [(18)F]FDG-PET in a Murine Model of Inflammation.

    PubMed

    Hovhannisyan, Narinée; Dhilly, Martine; Guillouet, Stéphane; Leporrier, Michel; Barré, Louisa

    2016-06-06

    Lymphoma research has advanced thanks to introduction of [(18)F]fludarabine, a positron-emitting tool. This novel radiotracer has been shown to display a great specificity for lymphoid tissues. However, in a benign process such as inflammation, the uptake of this tracer has not been questioned. Indeed, in inflammatory zones, elevated glucose metabolism rate may result in false-positives with [(18)F]FDG-PET Imaging. In the present investigation, it has been argued that cells, involved in inflammation, might be less avid of [(18)F]fludarabine. To generate inflammation, Swiss mice were intramuscularly injected with 0.1 mL of turpentine oil into the right front paw. Imaging sessions with (18)F-labeled tracers named above were conducted on days 5 and 25 after inoculation. For each animal, volumes of interest (VOI), delineating the muscle of the inflamed (IP) and normal paws (NP), were determined on PET scans. For characterization of inflammation, muscle samples from IP and NP were stained with hematoxylin and eosin (H&E). In early (day 5) inflammation, [(18)F]FDG accumulation was 4.00 ± 1.65 times greater in the IP than in the contralateral NP; for [(18)F]fludarabine, this IP/NP ratio was 1.31 ± 0.28, resulting in a significant difference between radiotracer groups (p < 0.01). In late (day 25) inflammation, the IP/NP ratios were 2.07 ± 0.49 and 1.03 ± 0.07, for [(18)F]FDG and [(18)F]fludarabine, respectively (p < 0.001). [(18)F]Fludarabine showed significantly weaker uptake in inflammation when compared with [(18)F]FDG. This encouraging finding suggests that [(18)F]fludarabine-PET might well be a robust approach for distinguishing tumor from inflammatory tissue, avoiding false-positive PET results and thus enabling an accurate imaging of lymphoma.

  10. Radiation absorbed dose estimates for 18F-BPA PET.

    PubMed

    Kono, Yuzuru; Kurihara, Hiroaki; Kawamoto, Hiroshi; Yasui, Naoko; Honda, Naoki; Igaki, Hiroshi; Itami, Jun

    2017-01-01

    Background Boron neutron capture therapy (BNCT) is a molecular radiation therapy approach based on the (10)B (n, α) (7)Li nuclear reaction in cancer cells. In BNCT, delivery of (10)B in the form of 4-borono-phenylalanine conjugated with fructose (BPA-fr) to the cancer cells is important. The PET tracer 4-borono-2-18F-fluoro-phenylalanine (FBPA) has been used to predict the accumulation of BPA-fr before BNCT. Purpose To determine the biodistribution and dosimetric parameters in 18F-BPA PET/CT studies. Material and Methods Human biokinetic data were obtained during clinical 18F-BPA PET studies between February and June 2015 at one institution. Nine consecutive patients were studied prospectively. The internal radiation dose was calculated on the basis of radioactivity data from blood, urine, and normal tissue of the heart, liver, spleen, kidney, and other parts of the body at each time point using OLINDA/EXM1.1 program. We compared our calculations with published 18F-FDG data. Results Adult patients (3 men, 3 women; age range, 28-68 years) had significantly smaller absorbed doses than pediatric patients (3 patients; age range, 5-12 years) ( P = 0.003). The mean effective dose was 57% lower in adult patients compared with pediatric patients. Mean effective doses for 18F-BPA were 25% lower than those for 18F-FDG presented in International Commission of Radiation Protection (ICRP) publication 106. Conclusion We found significant differences in organ absorbed doses for 18F-BPA against those for 18F-FDG presented in ICRP publication 106. Mean effective doses for 18F-BPA were smaller than those for 18F-FDG in the publication by 0.5-38% (mean difference, 25%).

  11. Vacuum ultraviolet field emission lamp consisting of neodymium ion doped lutetium fluoride thin film as phosphor.

    PubMed

    Yanagihara, Masahiro; Tsuji, Takayuki; Yusop, Mohd Zamri; Tanemura, Masaki; Ono, Shingo; Nagami, Tomohito; Fukuda, Kentaro; Suyama, Toshihisa; Yokota, Yuui; Yanagida, Takayuki; Yoshikawa, Akira

    2014-01-01

    A vacuum ultraviolet (VUV) field emission lamp was developed by using a neodymium ion doped lutetium fluoride (Nd(3+) : LuF3) thin film as solid-state phosphor and carbon nanofiber field electron emitters. The thin film was synthesized by pulsed laser deposition and incorporated into the lamp. The cathodoluminescence spectra of the lamp showed multiple emission peaks at 180, 225, and 255 nm. These emission spectra were in good agreement with the spectra reported for the Nd(3+) : LuF3 crystal. Moreover, application of an acceleration voltage effectively increased the emission intensity. These results contribute to the performance enhancement of the lamp operating in the VUV region.

  12. Vacuum Ultraviolet Field Emission Lamp Consisting of Neodymium Ion Doped Lutetium Fluoride Thin Film as Phosphor

    PubMed Central

    Yanagihara, Masahiro; Tsuji, Takayuki; Yusop, Mohd Zamri; Tanemura, Masaki; Nagami, Tomohito; Fukuda, Kentaro; Suyama, Toshihisa; Yokota, Yuui; Yanagida, Takayuki; Yoshikawa, Akira

    2014-01-01

    A vacuum ultraviolet (VUV) field emission lamp was developed by using a neodymium ion doped lutetium fluoride (Nd3+ : LuF3) thin film as solid-state phosphor and carbon nanofiber field electron emitters. The thin film was synthesized by pulsed laser deposition and incorporated into the lamp. The cathodoluminescence spectra of the lamp showed multiple emission peaks at 180, 225, and 255 nm. These emission spectra were in good agreement with the spectra reported for the Nd3+ : LuF3 crystal. Moreover, application of an acceleration voltage effectively increased the emission intensity. These results contribute to the performance enhancement of the lamp operating in the VUV region. PMID:25302320

  13. sup 18 F-labeled insulin: A prosthetic group methodology for incorporation of a positron emitter into peptides and proteins

    SciTech Connect

    Shai, Y.; Kirk, K.L.; Channing, M.A.; Dunn, B.B.; Lesniak, M.A.; Eastman, R.C.; Finn, R.D.; Roth, J.; Jacobson, K.A. )

    1989-05-30

    In the present study we synthesize {sup 18}F-labeled insulin of high specific radioactivity. A new prosthetic group methodology, in which ({sup 18}F)fluoride displaces a bromide group of 4-(bromomethyl)-benzoylamine intermediates, was used. The 4-(fluoromethyl)benzoyl product was chemically stable. {sup 18}F-Labeled insulin retains the essential biological properties of native insulin, as measured in vitro by binding to insulin receptors on human cells and stimulation of glucose metabolism in rat adipocytes. The overall process can be carried out speedily to yield a product of sufficient purity to permit in vivo studies. The method appears to be applicable to a wide variety of peptides.

  14. Automated synthesis and dosimetry of 6-deoxy-6-[18F]fluoro-D-fructose (6-[18F]FDF): a radiotracer for imaging of GLUT5 in breast cancer

    PubMed Central

    Bouvet, Vincent; Jans, Hans S; Wuest, Melinda; Soueidan, Olivier-Mohamad; Mercer, John; McEwan, Alexander JB; West, Frederick G; Cheeseman, Chris I; Wuest, Frank

    2014-01-01

    6-Deoxy-6-[18F]fluoro-D-fructose (6-[18F]FDF) is a promising PET radiotracer for imaging GLUT5 in breast cancer. The present work describes GMP synthesis of 6-[18F]FDF in an automated synthesis unit (ASU) and dosimetry calculations to determine radiation doses in humans. GMP synthesis and dosimetry calculations are important prerequisites for first-in-human clinical studies of 6-[18F]FDF. The radiochemical synthesis of 6-[18F]FDF was optimized and adapted to an automated synthesis process using a Tracerlab FXFN ASU (GE Healthcare). Starting from 30 GBq of cyclotron-produced n.c.a. [18F]fluoride, 2.9 ± 0.1 GBq of 6-[18F]FDF could be prepared within 50 min including HPLC purification resulting in an overall decay-corrected radiochemical yield of 14 ± 3% (n = 11). Radiochemical purity exceeded 95%, and the specific activity was greater than 5.1 GBq/μmol. Sprague-Dawley rats were used for biodistribution experiments, and dynamic and static small animal PET experiments. Biodistribution studies served as basis for allometric extrapolation to the standard man anatomic model and normal organ-absorbed dose calculations using OLINDA/EXM software. The calculated human effective dose for 6-[18F]FDF was 0.0089 mSv/MBq. Highest organ doses with a dose equivalent of 0.0315 mSv/MBq in a humans were found in bone. Injection of 370 MBq (10 mCi) of 6-[18F]FDF results in an effective whole body radiation dose of 3.3 mSv in humans, a value comparable to that of other 18F-labeled PET radiopharmaceuticals. The optimized automated synthesis under GMP conditions, the good radiochemical yield and the favorable human radiation dosimetry estimates support application of 6-[18F]FDF in clinical trials for molecular imaging of GLUT5 in breast cancer patients. PMID:24795839

  15. Pharmacokinetic evaluation of the tau PET radiotracer [18F]T807 ([18F]AV-1451) in human subjects.

    PubMed

    Wooten, Dustin; Guehl, Nicolas J; Verwer, Eline E; Shoup, Timothy M; Yokell, Daniel L; Zubcevik, Nevena; Vasdev, Neil; Zafonte, Ross D; Johnson, Keith A; El Fakhri, Georges; Normandin, Marc David

    2016-09-22

    [(18)F]T807 is a PET radiotracer developed for imaging tau protein aggregates, which are implicated in neurological disorders including Alzheimer's disease (AD) and traumatic brain injury (TBI). The current study characterizes [(18)F]T807 pharmacokinetics in human subjects using dynamic PET imaging and metabolite-corrected arterial input functions.

  16. Trojan Horse Method and RIBs: The 18F(p,α)15O reaction at astrophysical energies

    NASA Astrophysics Data System (ADS)

    Cherubini, S.; Gulino, M.; Rapisarda, G. G.; Spitaleri, C.; La Cognata, M.; Lamia, L.; Kubono, S.; Yamaguchi, H.; Hayakawa, S.; Wakabayashi, Y.; Iwasa, N.; Kato, S.; Komatsubara, H.; Teranishi, T.; Coc, A.; De Séréville, N.; Hammache, F.

    2012-11-01

    The abundance of 18F in Nova explosions is an important issue for the understanding of this astrophysical phenomenon. For this reason it is necessary to study the nuclear reactions that produce or destroy this isotope in novae. Among these latter processes, the 18F(p,α)15O is one of the main 18F destruction channels. We report here on the preliminary results of the first experiment that applies the Trojan Horse Method to a Radioactive Ion Beam induced reaction. The experiment was performed using the CRIB apparatus of the Center for Nuclear Study of The Tokyo University.

  17. Effect of humic substances aggregation on the determination of fluoride in water using an ion selective electrode.

    PubMed

    Shen, Junjie; Gagliardi, Simona; McCoustra, Martin R S; Arrighi, Valeria

    2016-09-01

    The control of drinking water quality is critical in preventing fluorosis. In this study humic substances (HS) are considered as representative of natural organic matter (NOM) in water. We show that when HS aggregate the response of fluoride ion selective electrodes (ISE) may be perturbed. Dynamic light scattering (DLS) results of both synthetic solutions and natural water sample suggest that low pH and high ionic strength induce HS aggregation. In the presence of HS aggregates, fluoride concentration measured by ISE has a reduction up to 19%. A new "open cage" concept has been developed to explain this reversible phenomenon. The interference of HS aggregation on fluoride measurement can be effectively removed by centrifugation pretreatment.

  18. In vivo biodistribution of two ( sup 18 F)-labelled muscarinic cholinergic receptor ligands: 2-( sup 18 F)- and 4-( sup 18 F)-fluorodexetimide

    SciTech Connect

    Wilson, A.A.; Scheffel, U.A.; Dannals, R.F.; Stathis, M.; Ravert, H.T.; Wagner, H.N. Jr. )

    1991-01-01

    Two ({sup 18}F)-labelled analogues of the potent muscarinic cholinergic receptor (m-AChR) antagonist, dexetimide, were evaluated as potential ligands for imaging m-AChR by positron emission tomography (PET). Intravenous administration of both 2-({sup 18}F)- or 4-({sup 18}F)-fluorodexetimide resulted in high brain uptake of radioactivity in mice. High binding levels were observed in m-AChR rich areas, such as cortex and striatum, with low levels in the receptor-poor cerebellum. Uptake of radioactivity was saturable and could be blocked by pre-administration of dexetimide or atropine. Drugs with different sites of action were ineffective at blocking receptor binding. The results indicate that both radiotracers are promising candidates for use in PET studies.

  19. Lithium-fluoride flashover ion source cleaned with a glow discharge and irradiated with vacuum-ultraviolet radiation

    SciTech Connect

    Burns, E.J.T.; Woodworth, J.R.; Bieg, K.W.; Mehlhorn, T.A.; Stygar, W.A.; Sweeney, M.A.

    1988-01-01

    We have studied methods of varying the ion species generated by a lithium-fluoride overcoated anode in a 0.5-MV magnetically insulated ion diode. We found that cleaning the anode surface with a 13.6-MHz rf glow discharge or illuminating the anode with a pulsed soft x-ray, vacuum-ultraviolet (XUV) radiation source just before the accelerator pulse significantly altered the ion species of the ion beam produced by the diode. The glow-discharge plasma removed adsorbates (carbon, hydrogen, and oxygen) from the surface of the LiF flashover source. The ions seen were lithium and hydrogen. Unfortunately, the diode impedance with a lithium-fluoride anode was high and the ion efficiency was low; however, XUV irradiation of the surface dramatically lowered the impedance by desorbing neutrals from the ion source via photon-stimulated desorption. Current densities of ten times the Child--Langmuir space-charge limit were achieved under XUV irradiation. In particular, ion currents increased by over a factor of 3 when 12 mJ/cm/sup 2/ of XUV radiation was used. However, with XUV irradiation the largest fraction of ions were fluorine, oxygen, carbon, and hydrogen, not lithium.

  20. In-Depth Characterization of N-Linked Oligosaccharides Using Fluoride-Mediated Negative Ion Microfluidic Chip LC-MS

    PubMed Central

    Ni, Wenqin; Bones, Jonathan; Karger, Barry L.

    2013-01-01

    Characterization of N-glycans by liquid chromatography-positive electrospray ionization (ESI) tandem mass spectrometry (LC-MS/MS) using a microfluidic chip packed with porous graphitized carbon (PGC) represents a rapidly developing area in oligosaccharide analysis. Positive ion ESI-MS generates B/Y-type glycosidic fragment ions under collisional induced dissociation (CID). Although these ions facilitate glycan sequencing, they provide little information on linkage and positional isomers. Isomer identification in these cases is by retention on the PGC stationary phase where the specific structural isomers can, in principle, be separated. In this paper, we broaden the applicability of the PGC microfluidic chip/MS platform by implementing fluoride-mediated negative ESI-MS. Ammonium fluoride, added to the mobile phase, aids in the formation of pseudomolecular oligosaccharide anions due to the ability of fluoride to abstract a proton from the glycan structure. The negative charge results in the generation of C-type glycosidic fragments, highly informative A-type cross ring fragment ions and additional gas phase ion reaction products (e.g., D- and E-type ions), which, when combined, lead to in-depth oligosaccharide characterization, including linkage and positional isomers. Due to the separation of anomers by the PGC phase, comparison of oligosaccharides with an intact reducing terminus to their corresponding alditols was performed, revealing a more sensitive MS and, especially, MS/MS response from the glycans with a free reducing end. Fluoride also ensured recovery of charged oligosaccharides from the PGC stationary phase. Application to the characterization of N-glycans released from polyclonal human and murine serum IgG is presented to demonstrate the effectiveness of the chip/negative ESI approach. PMID:23398125

  1. Design of an Automated System for Synthesis of [18 F] FDG for PET Investigation at IFIN-HH Bucharest

    NASA Astrophysics Data System (ADS)

    Craciun, Liviu Stefan; Cimpeanu, Catalina; Constantinescu, Olimpiu; Dudu, Dorin; Ionescu, Cristina; Negoita, Nicolae; Racolta, Petru Mihai; Rusen, Ion

    2009-03-01

    A novel apparatus constructed at IFIN-HH is described for automated synthesis of radiopharmaceuticals labeled with 18F for use in positron emission tomography (PET) investigations. [18 F] fluoride was produced at the IFIN-HH cyclotron by irradiation of H2O enriched 97% in 18O with 13 MeV deuterons, or 8 MeV protons. The irradiated H2O was transferred (injected) into the radiochemical fully-automated processing systems which ensured the separation of 18F from H2O, the labeling with 18F, and finally purified by filtration with selective absorbants. The system is easy to operate and contains a programmable logical controller that manages the entire operation program stored in its internal memory. The computer is used to assist the operator during the different steps of synthesis and to allow visualization of the process and printing the report. The device was used for used for the production of 2-[18 F] FLUORO-2-DEOXY-D-GLUCOSE at the IFIN-HH cyclotron, one of the most used radiopharmaceutical in PET investigations. The synthesis module is configured so that is flexible enough to accomplish other nucleophile reactions of labeling with short lived radioisotopes.

  2. High 18F-fluorodeoxyglucose (18F-FDG) uptake in microscopic peritoneal tumors requires physiological hypoxia

    PubMed Central

    Li, Xiao-Feng; Ma, Yuanyuan; Sun, Xiaorong; Humm, John L.; Ling, C. Clifton; O’Donoghue, Joseph A.

    2010-01-01

    The objective of this study was to examine 18F-fluorodeoxyglucose (18F-FDG) uptake in microscopic tumors grown intraperitoneally in nude mice and to relate this to physiological hypoxia and glucose transporter-1 (GLUT-1) expression. Methods Human colon cancer HT29 and HCT-8 cells were injected intraperitoneally into nude mice to generate disseminated tumors of varying sizes. Following overnight fasting, animals, either breathing air or carbogen (95% O2+ 5% CO2), were intravenously administered 18F-FDG together with the hypoxia marker pimonidazole (PIMO) and the cellular proliferation marker bromodeoxyuridine (BrdUrd) one hour before sacrifice. Hoechst 33342, a perfusion marker, was administered one minute before sacrifice. Following sacrifice, the intratumoral distribution of 18F-FDG was assessed by digital autoradiography of frozen tissue sections. This was compared with the distributions of PIMO, GLUT-1 expression, BrdUrd and Hoechst 33342 as visualized by immunofluorescent microscopy. Results Small tumors (< 1 mm diameter) had high 18F-FDG accumulation and were severely hypoxic with high GLUT-1 expression. Larger tumors (1–4 mm diameter) generally had low 18F-FDG accumulation and were not significantly hypoxic with low GLUT1 expression. Carbogen breathing significantly decreased 18F-FDG accumulation and tumor hypoxia in microscopic tumors but had little effect on GLUT1 expression. Conclusion There was high 18F-FDG uptake in microscopic tumors which was spatially associated with physiological hypoxia and high GLUT-1 expression. This enhanced uptake was abrogated by carbogen breathing, indicating that in the absence of physiological hypoxia, high GLUT1 expression, by itself, was insufficient to ensure high 18F-FDG uptake. PMID:20351353

  3. Automation of [(18) F]fluoroacetaldehyde synthesis: application to a recombinant human interleukin-1 receptor antagonist (rhIL-1RA).

    PubMed

    Morris, Olivia; McMahon, Adam; Boutin, Herve; Grigg, Julian; Prenant, Christian

    2016-06-15

    [(18) F]Fluoroacetaldehyde is a biocompatible prosthetic group that has been implemented pre-clinically using a semi-automated remotely controlled system. Automation of radiosyntheses permits use of higher levels of [(18) F]fluoride whilst minimising radiochemist exposure and enhancing reproducibility. In order to achieve full-automation of [(18) F]fluoroacetaldehyde peptide radiolabelling, a customised GE Tracerlab FX-FN with fully programmed automated synthesis was developed. The automated synthesis of [(18) F]fluoroacetaldehyde is carried out using a commercially available precursor, with reproducible yields of 26% ± 3 (decay-corrected, n = 10) within 45 min. Fully automated radiolabelling of a protein, recombinant human interleukin-1 receptor antagonist (rhIL-1RA), with [(18) F]fluoroacetaldehyde was achieved within 2 h. Radiolabelling efficiency of rhIL-1RA with [(18) F]fluoroacetaldehyde was confirmed using HPLC and reached 20% ± 10 (n = 5). Overall RCY of [(18) F]rhIL-1RA was 5% ± 2 (decay-corrected, n = 5) within 2 h starting from 35 to 40 GBq of [(18) F]fluoride. Specific activity measurements of 8.11-13.5 GBq/µmol were attained (n = 5), a near three-fold improvement of those achieved using the semi-automated approach. The strategy can be applied to radiolabelling a range of peptides and proteins with [(18) F]fluoroacetaldehyde analogous to other aldehyde-bearing prosthetic groups, yet automation of the method provides reproducibility thereby aiding translation to Good Manufacturing Practice manufacture and the transformation from pre-clinical to clinical production.

  4. Newer PET application with an old tracer: role of 18F-NaF skeletal PET/CT in oncologic practice.

    PubMed

    Bastawrous, Sarah; Bhargava, Puneet; Behnia, Fatemeh; Djang, David S W; Haseley, David R

    2014-01-01

    The skeleton is one of the most common sites for metastatic disease, particularly from breast and prostate cancer. Bone metastases are associated with considerable morbidity, and accurate imaging of the skeleton is important in determining the appropriate therapeutic plan. Sodium fluoride labeled with fluorine 18 (sodium fluoride F 18 [(18)F-NaF]) is a positron-emitting radiopharmaceutical first introduced several decades ago for skeletal imaging. (18)F-NaF was approved for clinical use as a positron emission tomographic (PET) agent by the U.S. Food and Drug Administration in 1972. The early use of this agent was limited, given the difficulties of imaging its high-energy photons on the available gamma cameras. For skeletal imaging, it was eventually replaced by technetium 99m ((99m)Tc)-labeled agents because of the technical limitations of (18)F-NaF. During the past several years, the widespread availability and implementation of hybrid PET and computed tomographic (CT) dual-modality systems (PET/CT) have encouraged a renewed interest in (18)F-NaF PET/CT for routine clinical use in bone imaging. Because current PET/CT systems offer high sensitivity and spatial resolution, the use of (18)F-NaF has been reevaluated for the detection of malignant and nonmalignant osseous disease. Growing evidence suggests that (18)F-NaF PET/CT provides increased sensitivity and specificity in the detection of bone metastases. Furthermore, the favorable pharmacokinetics of (18)F-NaF, combined with the superior imaging characteristics of PET/CT, supports the routine clinical use of (18)F-NaF PET/CT for oncologic imaging for skeletal metastases. In this article, a review of the indications, imaging appearances, and utility of (18)F-NaF PET/CT in the evaluation of skeletal disease is provided, with an emphasis on oncologic imaging.

  5. Fabrication of an electrochemical sensor based on spiropyran for sensitive and selective detection of fluoride ion.

    PubMed

    Tao, Jia; Zhao, Peng; Li, Yinhui; Zhao, Wenjie; Xiao, Yue; Yang, Ronghua

    2016-04-28

    In the past decades, numerous electrochemical sensors based on exogenous electroactive substance have been reported. Due to non-specific interaction between the redox mediator and the target, the instability caused by false signal may not be avoided. To address this issue, in this paper, a new electrochemical sensor based on spiropyran skeleton, namely SPOSi, was designed for specific electrochemical response to fluoride ions (F(-)). The breakage of Si-O induced by F(-) based on the specific nucleophilic substitution reaction between F(-) and silica would directly produce a hydroquinone structure for electrochemical signal generation. To improve the sensitivity, SPOSi probe was assembled on the single-walled carbon nanotubes (SWCNTs) modified glassy carbon electrode (GCE) through the π-π conjugating interaction. This electrode was successfully applied to monitor F(-) with a detection limit of 8.3 × 10(-8) M. Compared with the conventional F(-) ion selected electrode (ISE) which utilized noncovalent interaction, this method displays higher stability and a comparable sensitivity in the urine samples.

  6. Electrospun montmorillonite modified poly(vinylidene fluoride) nanocomposite separators for lithium-ion batteries

    SciTech Connect

    Fang, Changjiang; Yang, Shuli; Zhao, Xinfei; Du, Pingfan; Xiong, Jie

    2016-07-15

    Highlights: • Composite separators of PVDF and MMT for lithium-ion batteries were electrospun. • Thermal dimensional stability and tensile property of composite separators get improved. • Presence of montmorillonite promotes electrical properties of PVDF fibrous separators. • Batteries consisting of PVDF/MMT-5% separator achieve the best performance. - Abstract: Composite separators of poly(vinylidene fluoride) (PVDF) with different contents of montmorillonite (MMT) for Li-ion batteries have been fabricated by electrospinning. The morphology, function group, crystallinity, and mechanical properties of membranes were investigated by scanning electron microscope (SEM), Fourier Transform infrared spectra (FT-IR), differential scanning calorimetry (DSC), and tensile test, respectively. Interlayer spacing of MMT in polymer was characterized by X-ray diffraction (XRD). In addition, the results of electrochemical measurements suggest that PVDF/MMT-5% composite membrane has maximum ionic conductivity of 4.2 mS cm{sup −1}, minimum interfacial resistance of 97 Ω, and excellent electrochemical stability. The cell comprising PVDF/MMT-5% composite membrane shows higher capacity and more stable cycle performance than the one using commercial Celgard PP membrane.

  7. Concerted nucleophilic aromatic substitution with 19F- and 18F-

    NASA Astrophysics Data System (ADS)

    Neumann, Constanze N.; Hooker, Jacob M.; Ritter, Tobias

    2016-06-01

    Nucleophilic aromatic substitution (SNAr) is widely used by organic chemists to functionalize aromatic molecules, and it is the most commonly used method to generate arenes that contain 18F for use in positron-emission tomography (PET) imaging. A wide range of nucleophiles exhibit SNAr reactivity, and the operational simplicity of the reaction means that the transformation can be conducted reliably and on large scales. During SNAr, attack of a nucleophile at a carbon atom bearing a ‘leaving group’ leads to a negatively charged intermediate called a Meisenheimer complex. Only arenes with electron-withdrawing substituents can sufficiently stabilize the resulting build-up of negative charge during Meisenheimer complex formation, limiting the scope of SNAr reactions: the most common SNAr substrates contain strong π-acceptors in the ortho and/or para position(s). Here we present an unusual concerted nucleophilic aromatic substitution reaction (CSNAr) that is not limited to electron-poor arenes, because it does not proceed via a Meisenheimer intermediate. We show a phenol deoxyfluorination reaction for which CSNAr is favoured over a stepwise displacement. Mechanistic insights enabled us to develop a functional-group-tolerant 18F-deoxyfluorination reaction of phenols, which can be used to synthesize 18F-PET probes. Selective 18F introduction, without the need for the common, but cumbersome, azeotropic drying of 18F, can now be accomplished from phenols as starting materials, and provides access to 18F-labelled compounds not accessible through conventional chemistry.

  8. Mechanism of Electrophilic Fluorination with Pd(IV): Fluoride Capture and Subsequent Oxidative Fluoride Transfer†, ‡

    PubMed Central

    Brandt, Jochen R.; Lee, Eunsung; Boursalian, Gregory B.

    2013-01-01

    Electrophilic fluorinating reagents derived from fluoride are desirable for the synthesis of 18F-labeled molecules for positron emission tomography (PET). Here, we study the mechanism by which a Pd(IV)-complex captures fluoride and subsequently transfers it to nucleophiles. The intermediate Pd(IV)-F is formed with high rates even at the nano- to micromolar fluoride concentrations typical for radiosyntheses with 18F due to fast formation of an outer-sphere complex between fluoride and Pd(IV). The subsequent fluorine transfer from the Pd(IV)-F complex is proposed to proceed through an unusual SET/fluoride transfer/SET mechanism. The findings detailed in this manuscript provide a theoretical foundation suitable for addressing a more general approach for electrophilic fluorination with high specific activity 18F PET imaging. PMID:24376910

  9. Cationic boranes for the complexation of fluoride ions in water below the 4 ppm maximum contaminant level.

    PubMed

    Kim, Youngmin; Gabbaï, François P

    2009-03-11

    In search of a molecular receptor that could bind fluoride ions in water below the maximum contaminant level of 4 ppm set by the Environmental Protection Agency (EPA), we have investigated the water stability and fluoride binding properties of a series of phosphonium boranes of general formula [p-(Mes(2)B)C(6)H(4)(PPh(2)R)](+) with R = Me ([1](+)), Et ([2](+)), n-Pr ([3](+)), and Ph ([4](+)). These phosphonium boranes are water stable and react reversibly with water to form the corresponding zwitterionic hydroxide complexes of general formula p-(Mes(2)(HO)B)C(6)H(4)(PPh(2)R). They also react with fluoride ions to form the corresponding zwitterionic fluoride complexes of general formula p-(Mes(2)(F)B)C(6)H(4)(PPh(2)R). Spectrophotometric acid-base titrations carried out in H(2)O/MeOH (9:1 vol.) afford pK(R+) values of 7.3(+/-0.07) for [1](+), 6.92(+/-0.1) for [2](+), 6.59(+/-0.08) for [3](+), and 6.08(+/-0.09) for [4](+), thereby indicating that the Lewis acidity of the cationic boranes increases in following order: [1](+) < [2](+) < [3](+) < [4](+). In agreement with this observation, fluoride titration experiments in H(2)O/MeOH (9:1 vol.) show that the fluoride binding constants (K = 840(+/-50) M(-1) for [1](+), 2500(+/-200) M(-1) for [2](+), 4000(+/-300) M(-1) for [3](+), and 10 500(+/-1000) M(-1) for [4](+)) increase in the same order. These results show that the Lewis acidity of the cationic boranes increases with their hydrophobicity. The resulting Lewis acidity increase is substantial and exceeds 1 order of magnitude on going from [1](+) to [4](+). In turn, [4](+) is sufficiently fluorophilic to bind fluoride ions below the EPA contaminant level in pure water. These results indicate that phosphonium boranes related to [4](+) could be used as molecular recognition units in chemosensors for drinking water analysis.

  10. Structural changes of conversion metal fluoride cathodes in lithium ion batteries

    NASA Astrophysics Data System (ADS)

    Sina, Mahsa

    Currently, cathode materials for Li-ion batteries are based on intercalation processes where, during charge and discharge processes, Li intercalates into the crystal lattice while maintaining the host crystal structure. More recently, new cathode materials have been introduced based on conversion reactions involving phase transformation and complete reduction of the host transition metal. In addition, conversion reactions involve two or more Li ions with a resulting much higher capacity than obtainable for intercalation materials. However, mechanism of phase transformation and cycling reversibility are at present still poorly understood. In this study transmission electron microscopy (TEM) techniques including selected area electron diffraction (SAED) pattern, annular dark field (ADF) STEM image, and electron energy loss spectroscopy (EELS) with nanoscale spatial resolution were used to study the phase evolution and structural changes of iron fluorides (FeFe2, FeO0.7F 1.3, FeF3) after various discharge/charge cycles. Additionally, the changes of the Fe valence states upon cycling were determined using EELS by measuring the L3/L2 intensity ratio of Fe-L edge. The structural transformations of FeO0.7F1.3 during the first lithiation show that litiahation contains two regions. The first region, lithiation is an intercalation reaction with reduction of Fe 3+ to Fe2+. The second region of lithiation involves a conversion reaction, with the formation of metallic Fe, LiF, and Li 0.7Fe2+0.5O0.7F0.3 (rocksalt type) phases. The first delithiation process follows a different conversion reaction path compared to the first lithiation reaction involving the formation an amorphous rutile-type phase along with with the rocksalt-type phase. Interestingly, upon full recharge (delithiated electrode), the measured average Fe valence state returns back to its initial value of Fe2.7+. The growth of a solid electrolyte interphase (SEI) layer formation at the electrode

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

    PubMed

    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.

  12. A preliminary investigation of lithogenic and anthropogenic influence over fluoride ion chemistry in the groundwater of the southern coastal city, Tamilnadu, India.

    PubMed

    Selvam, S

    2015-03-01

    A total of 72 groundwater samples were collected from open wells and boreholes during pre- and post-monsoon periods in Tuticorin. Samples were analyzed for physicochemical properties, major cations, and anions in the laboratory using the standard methods given by the American Public Health Association. The fluoride concentration was analyzed in the laboratory using Metrohm 861 advanced compact ion chromatography. The geographic information system-based spatial distribution map of different major elements has been prepared using ArcGIS 9.3. The fluoride concentration ranges between 0.16 mg/l and 4.8 mg/l during pre-monsoon and 0.2-3.2 mg/l during post-monsoon. Alkaline pH, low calcium concentrations, high groundwater temperatures, and semiarid climatic conditions of the study area may cause elevated fluoride concentrations in groundwater, by increasing the solubility of fluoride-bearing formations (fluoride). Linear trend analysis on seasonal and annual basis clearly depicted that fluoride pollution in the study area is increasing significantly. Fluoride concentrations showed positive correlations with those of Na(+) and HCO3 (-) and negative correlations with Ca(2+) and Mg(2+). The alkaline waters were saturated with calcite in spite of the low Ca(2+) concentrations. Northwestern parts of the study area are inherently enriched with fluorides threatening several ecosystems. The saturation index indicates that dissolution and precipitation contribute fluoride dissolution along with mixing apart from anthropogenic activities.

  13. Photomodulation of fluoride ion binding through anion-π interactions using a photoswitchable azobenzene system

    PubMed Central

    Rananaware, Anushri; Samanta, Mousumi; Bhosale, Rajesh S.; Kobaisi, Mohammad Al; Roy, Biswajit; Bheemireddy, Varun; Bhosale, Sidhanath V.; Bandyopadhyay, Subhajit; Bhosale, Sheshanath V.

    2016-01-01

    The discovery of photoswitchable azobenzene-systems that undergo trans-to-cis photoisomerisation was a milestone in supramolecular chemistry. Such photoswitches have possible applications in data storage, stimuli responsive delivery systems, and molecular machines due to fast and selective switching. However, the light induced cis isomer of azobenzene is rather unstable and reverts thermally and photochemically to the thermodynamically stable trans configuration. We report, for the first time, controlled photoswitching of an azo-naphthalenediimide (azo-NDI) which can be achieved upon binding of fluoride ions through anion-π interaction. This NDI-F–NDI “sandwich” stabilises the cis configuration through the generation of an NDI•− radical anion, and a dianionic, NDI2− species that becomes unusually stable in the cis form. The sandwiched cis form reverts to the trans form only upon decomplexation of F−. A model pollutant was successfully degraded using the photogenerated NDI-F–NDI sandwich. This opens a wide range of applications in molecular and supramolecular nanotechnology. PMID:26953168

  14. In vitro reconstituted biotransformation of 4-fluorothreonine from fluoride ion: application of the fluorinase.

    PubMed

    Deng, Hai; Cross, Stuart M; McGlinchey, Ryan P; Hamilton, John T G; O'Hagan, David

    2008-12-22

    In this paper, we report that fluoride ion is converted to the amino acid/antibiotic 4-fluorothreonine 2 in a biotransformation involving five (steps a-e) overexpressed enzymes. The biotransformation validates the biosynthetic pathway to 4-fluorothreonine in the bacterium Streptomyces cattleya (Schaffrath et al., 2002). To achieve an in vitro biotransformation, the fluorinase and the purine nucleoside phosphorylase (PNP) enzymes (steps a and b), which are coded for by the flA and flB genes of the fluorometabolite gene cluster in S. cattleya, were overexpressed. Also, an isomerase gene product that can convert 5-FDRP 6 to 5-FDRibulP 7 (step c) was identified in S. cattleya, and the enzyme was overexpressed for the biotransformation. A fuculose aldolase gene from S. coelicolor was overexpressed in E. coli and was used as a surrogate aldolase (step d) in these experiments. To complete the complement of enzymes, an ORF coding the PLP-dependent transaldolase, the final enzyme of the fluorometabolite pathway, was identified in genomic DNA by a reverse genetics approach, and the S. cattleya gene/enzyme was then overexpressed in S. lividans. This latter enzyme is an unusual PLP-dependent catalyst with some homology to both bacterial serine hydroxymethyl transferases (SHMT) and C5 sugar isomerases/epimerases. The biotransformation demonstrates the power of the fluorinase to initiate C-F bond formation for organo-fluorine synthesis.

  15. Determination of Stability Constants of Hydrogen and Aluminum Fluorides with a Fluoride-Selective Electrode

    SciTech Connect

    Baumann, E.W.

    2003-01-06

    The ability to directly determine free fluoride ion concentration (or mean activity) simplifies gathering and interpretation of experimental data for studies of metal complexes. In this work, the new lanthanum fluoride electrode was used to measure free fluoride ion in an investigation of the hydrogen-fluoride and aluminum-fluoride systems in NH4NO3.

  16. New Developments in Chiral Cooperative Ion Pairing Organocatalysis by Means of Ammonium Oxyanions and Fluorides: From Protonation to Deprotonation Reactions.

    PubMed

    Legros, Fabien; Oudeyer, Sylvain; Levacher, Vincent

    2016-10-13

    This personal account summarizes our contribution to the ion pairing organocatalysis mainly by use of chiral quaternary or tertiary ammonium fluorides, aryloxides and carboxylates. Starting from an experimental observation, we were able to develop several approaches for the enantioselective protonation of silyl enolates and enol esters giving rise to chiral carbonyl compounds bearing a stereogenic center at the α-position. Moving from protonation to deprotonation reactions, chiral ammonium ion pair catalysts were successfully applied to several asymmetric transformations such as an Henry reaction or a direct vinylogous aldol reaction to cite a few. An outlook of further possible developments in this field of research will also be discussed.

  17. Conversion Reaction Mechanisms in Lithium Ion Batteries: Study of the Binary Metal Fluoride Electrodes

    SciTech Connect

    Wang, Feng; Robert, Rosa; Chernova, Natasha A.; Pereira, Nathalie; Omenya, Fredrick; Badway, Fadwa; Hua, Xiao; Ruotolo, Michael; Zhang, Ruigang; Wu, Lijun; Volkov, Vyacheslav; Su, Dong; Key, Baris; Whittingham, M. Stanley; Grey, Clare P.; Amatucci, Glenn G.; Zhu, Yimei; Graetz, Jason

    2015-10-15

    Materials that undergo a conversion reaction with lithium (e.g., metal fluorides MF{sub 2}: M = Fe, Cu, ...) often accommodate more than one Li atom per transition-metal cation, and are promising candidates for high-capacity cathodes for lithium ion batteries. However, little is known about the mechanisms involved in the conversion process, the origins of the large polarization during electrochemical cycling, and why some materials are reversible (e.g., FeF{sub 2}) while others are not (e.g., CuF{sub 2}). In this study, we investigated the conversion reaction of binary metal fluorides, FeF{sub 2} and CuF{sub 2}, using a series of local and bulk probes to better understand the mechanisms underlying their contrasting electrochemical behavior. X-ray pair-distribution-function and magnetization measurements were used to determine changes in short-range ordering, particle size and microstructure, while high-resolution transmission electron microscopy (TEM) and electron energy-loss spectroscopy (EELS) were used to measure the atomic-level structure of individual particles and map the phase distribution in the initial and fully lithiated electrodes. Both FeF{sub 2} and CuF{sub 2} react with lithium via a direct conversion process with no intercalation step, but there are differences in the conversion process and final phase distribution. During the reaction of Li{sup +} with FeF{sub 2}, small metallic iron nanoparticles (<5 nm in diameter) nucleate in close proximity to the converted LiF phase, as a result of the low diffusivity of iron. The iron nanoparticles are interconnected and form a bicontinuous network, which provides a pathway for local electron transport through the insulating LiF phase. In addition, the massive interface formed between nanoscale solid phases provides a pathway for ionic transport during the conversion process. These results offer the first experimental evidence explaining the origins of the high lithium reversibility in FeF{sub 2}. In contrast

  18. Synthesis, in vitro and in vivo evaluation of 3β-[18F]fluorocholic acid for the detection of drug-induced cholestasis in mice

    PubMed Central

    Neyt, Sara; Kersemans, Ken; Verhoeven, Jeroen; Devisscher, Lindsey; Van Vlierberghe, Hans; Vanhove, Christian; De Vos, Filip

    2017-01-01

    Introduction Drug-induced cholestasis is a liver disorder that might be caused by interference of drugs with the hepatobiliary bile acid transporters. It is important to identify this interference early on in drug development. In this work, Positron Emission Tomography (PET)-imaging with a 18F labeled bile acid analogue was introduced to detect disturbed hepatobiliary transport of bile acids. Methods 3β-[18F]fluorocholic acid ([18F]FCA) was prepared by nucleophilic substitution of a mesylated precursor with [18F]fluoride, followed by deprotection with sodium hydroxide. Transport of [18F]FCA was assessed in vitro using CHO-NTCP, HEK-OATP1B1, HEK-OATP1B3 transfected cells and BSEP & MRP2 membrane vesicles. Investigation of [18F]FCA metabolites was performed with primary mouse hepatocytes. Hepatobiliary transport of [18F]FCA was evaluated in vivo in wild-type, rifampicin and bosentan pretreated FVB-mice by dynamic μPET scanning. Results Radiosynthesis of [18F]FCA was achieved in a moderate radiochemical yield (8.11 ± 1.94%; non-decay corrected; n = 10) and high radiochemical purity (>99%). FCA was transported by the basolateral bile acid uptake transporters NTCP, OATP1B1 and OATP1B3. For canalicular efflux, BSEP and MRP2 are the relevant bile acid transporters. [18F]FCA was found to be metabolically stable. In vivo, [18F]FCA showed fast hepatic uptake (4.5 ± 0.5 min to reach 71.8 ± 1.2% maximum % ID) and subsequent efflux to the gallbladder and intestines (93.3 ± 6.0% ID after 1 hour). Hepatobiliary transport of [18F]FCA was significantly inhibited by both rifampicin and bosentan. Conclusion A 18F labeled bile acid analogue, [18F]FCA, has been developed that shows transport by NTCP, OATP, MRP2 and BSEP. [18F]FCA can be used as a probe to monitor disturbed hepatobiliary transport in vivo and accumulation of bile acids in blood and liver during drug development. PMID:28273180

  19. One-Proton Breakup of 18F and the 17O(p,γ)18F Reaction in Classical Novae

    NASA Astrophysics Data System (ADS)

    Isherwood, Bryan; Banu, A.; E491 Collaboration

    2013-10-01

    Classical nova studies are of considerable interest for understanding the chemical evolution of the Galaxy. They have been proposed as the most significant source for the nucleosynthesis of the isotopes 13C, 15N, and 17O in the Universe. Novae are also likely to synthesize the short-lived radioisotope 18F (T1/2 = 110 min), which is expected to be the most important contributor to the observed emission of 511 keV gamma radiation by space-based γ-ray telescopes. This emission is produced by electron-positron annihilation following the beta + decay of radioactive nuclei. A detection of these gamma rays could significantly constrain the nova simulation models. 18F nucleosynthesis in classical novae strongly depends on the thermonuclear rate of the 17O(p,γ)18F reaction, which is part of the CNO cycle. This work presents preliminary results toward determination of the 17O(p,γ)18F reaction cross section, which was measured by the indirect method of one-proton nuclear breakup at intermediate energies. The experiment was carried out at GANIL using a beam of 18F at 40 MeV/u impinging on a carbon target. Longitudinal momentum distributions of the 17O breakup fragments were measured in coincidence with γ-rays emitted by 17O residues.

  20. No-carrier-added (18F)-N-methylspiroperidol

    DOEpatents

    Shiue, Chyng-Yann; Fowler, Joanna S.; Wolf, Alfred P.

    1993-07-06

    There is disclosed a radioligand labeled with a positron emitting radionuclide suitable for dynamic study in living humans with positron emission transaxial tomography. [.sup.18 F]-N-methylspiroperidol, exhibiting extremely high affinity for the dopamine receptors, provides enhanced uptake and retention in the brain concomitant with reduced radiation burden. These characteristics all combine to provide [.sup.18 F]-N-methylspiroperidol as a radioligand superior to known radioligands for mapping dopamine receptors in normal and disease states in the living brain. Additionally, a new synthetic procedure for this material is disclosed.

  1. No-carrier-added (18F)-N-methylspiroperidol

    DOEpatents

    Shiue, Chyng-Yann; Fowler, Joanna S.; Wolf, Alfred P.

    1993-01-01

    There is disclosed a radioligand labeled with a positron emitting radionuclide suitable for dynamic study in living humans with positron emission transaxial tomography. [.sup.18 F]-N-methylspiroperidol, exhibiting extremely high affinity for the dopamine receptors, provides enhanced uptake and retention in the brain concomitant with reduced radiation burden. These characteristics all combine to provide [.sup.18 F]-N-methylspiroperidol as a radioligand superior to known radioligands for mapping dopamine receptors in normal and disease states in the living brain. Additionally, a new synthetic procedure for this material is disclosed.

  2. [18F]haloperidol binding in baboon brain in vivo.

    PubMed

    Yousef, K A; Fowler, J S; Volkow, N D; Dewey, S L; Shea, C; Schlyer, D J; Gatley, S J; Logan, J; Wolf, A P

    1996-01-01

    The binding of [18F]haloperidol to dopamine D2 and to sigma recognition sites in baboon brain was examined using positron emission tomography (PET). Studies were performed at baseline and after treatment with either haloperidol (to evaluate saturability), (+)-butaclamol (which has specificity for dopamine D2 receptors) or (-)-butaclamol (which has specificity for sigma sites). Binding was widespread. Treatment with (-)-butaclamol had no effect, whereas (+)-butaclamol selectively reduced the uptake in striatum. Haloperidol increased the clearance rate from all brain regions. These results indicate that the binding profile of [18F]haloperidol does not permit the selective examination of either dopamine D2 or sigma sites using PET.

  3. Radiosynthesis and 'click' conjugation of ethynyl-4-[(18)F]fluorobenzene--an improved [(18)F]synthon for indirect radiolabeling.

    PubMed

    Roberts, Maxine P; Pham, Tien Q; Doan, John; Jiang, Cathy D; Hambley, Trevor W; Greguric, Ivan; Fraser, Benjamin H

    2015-01-01

    Reproducible methods for [(18)F]radiolabeling of biological vectors are essential for the development of new [(18)F]radiopharmaceuticals. Molecules such as carbohydrates, peptides and proteins are challenging substrates that often require multi-step indirect radiolabeling methods. With the goal of developing more robust, time saving, and less expensive procedures for indirect [(18)F]radiolabeling of such molecules, our group has synthesized ethynyl-4-[(18)F]fluorobenzene ([(18)F]2, [(18)F]EYFB) in a single step (14 ± 2% non-decay corrected radiochemical yield (ndc RCY)) from a readily synthesized, shelf stable, inexpensive precursor. The alkyne-functionalized synthon [(18)F]2 was then conjugated to two azido-functionalized vector molecules via CuAAC reactions. The first 'proof of principle' conjugation of [(18)F]2 to 1-azido-1-deoxy-β-D-glucopyranoside (3) gave the desired radiolabeled product [(18)F]4 in excellent radiochemical yield (76 ± 4% ndc RCY (11% overall)). As a second example, the conjugation of [(18)F]2 to matrix-metalloproteinase inhibitor (5), which has potential in tumor imaging, gave the radiolabeled product [(18)F]6 in very good radiochemical yield (56 ± 12% ndc RCY (8% overall)). Total preparation time for [(18)F]4 and [(18)F]6 including [(18)F]F(-) drying, two-step reaction (nucleophilic substitution and CuAAC conjugation), two HPLC purifications, and two solid phase extractions did not exceed 70 min. The radiochemical purity of synthon [(18)F]2 and the conjugated products, [(18)F]4 and [(18)F]6, were all greater than 98%. The specific activities of [(18)F]2 and [(18)F]6 were low, 5.97 and 0.17 MBq nmol(-1), respectively.

  4. One-Step Synthesis of Titanium Oxyhydroxy-Fluoride Rods and Research on the Electrochemical Performance for Lithium-ion Batteries and Sodium-ion Batteries

    NASA Astrophysics Data System (ADS)

    Li, Biao; Gao, Zhan; Wang, Dake; Hao, Qiaoyan; Wang, Yan; Wang, Yongkun; Tang, Kaibin

    2015-10-01

    Titanium oxyhydroxy-fluoride, TiO0.9(OH)0.9F1.2 · 0.59H2O rods with a hexagonal tungsten bronze (HTB) structure, was synthesized via a facile one-step solvothermal method. The structure, morphology, and component of the products were characterized by X-ray powder diffraction (XRD), thermogravimetry (TG), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution TEM (HRTEM), inductively coupled plasma optical emission spectroscopy (ICP-OES), ion chromatograph, energy-dispersive X-ray (EDX) analyses, and so on. Different rod morphologies which ranged from nanoscale to submicron scale were simply obtained by adjusting reaction conditions. With one-dimension channels for Li/Na intercalation/de-intercalation, the electrochemical performance of titanium oxyhydroxy-fluoride for both lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs) was also studied. Electrochemical tests revealed that, for LIBs, titanium oxyhydroxy-fluoride exhibited a stabilized reversible capacity of 200 mAh g-1 at 25 mA g-1 up to 120 cycles in the electrode potential range of 3.0-1.2 V and 140 mAh g-1 at 250 mA g-1 up to 500 cycles, especially; for SIBs, a high capacity of 100 mAh g-1 was maintained at 25 mA g-1 after 115 cycles in the potential range of 2.9-0.5 V.

  5. Subchronic toxic effects of fluoride ion on the survival and behaviour of the aquatic snail Potamopyrgus antipodarum (Hydrobiidae, Mollusca).

    PubMed

    Alonso, Álvaro; Camargo, Julio A

    2011-04-01

    Short-term bioassays usually assess lethal effects of pollutants in animals, whereas subchronic bioassays are more suited for assessing effects on animal behaviour. Among them, videotaped bioassays are an improvement in the behavioural monitoring because they are easily and cheaply implemented. The present study focuses on the assessment of subchronic (14-day) effects of fluoride ion on the survival, proportion of dead plus immobile animals, and velocity (monitored by a videotaping and image analysis system) of the aquatic snail Potamopyrgus antipodarum (Hydrobiidae, Mollusca). One control and three nominal fluoride concentrations (5, 20, and 40 mg F(-)/l [actual mean concentrations of 5.2, 17.5, and 37.0 mg F(-)/l, respectively]) were used. Each treatment (including the control) was replicated 12 times. Mortality, number of dead plus immobile animals, and velocity were monitored after 0, 7, and 14 days of exposure. After 14 days, animals exposed to 40 mg F(-)/l showed higher mortality, number of dead, and immobile individuals than control animals. Snails exposed to 5 and 20 mg F(-)/l were not affected by fluoride ion regarding these endpoints. In contrast, snails exposed to 20 mg F(-)/l for 7 and 14 days showed lower velocity than control animals. Therefore, velocity was sensitive to environmental fluoride concentrations and as such is a useful parameter for ecologic risk assessment. In addition, videotaping allowed us to detect behavioural patrons in velocity at very short exposures (seconds) during the monitoring process by showing that the velocity of snails must be monitored at least during the course of several minutes. We conclude that in P. antipodarum, velocity is a more sensitive endpoint than the classic mortality and immobility endpoints.

  6. Fluorometric selective detection of fluoride ions in aqueous media using Ag doped CdS/ZnS core/shell nanoparticles.

    PubMed

    Boxi, Siddhartha Sankar; Paria, Santanu

    2016-01-14

    The presence of fluoride ions in drinking water plays an important role in human health. For that reason, maintaining the optimum concentration of fluoride ions in drinking water is essential, as both low and excess (above the permissible level) concentrations can cause different health problems, such as fluorosis, urolithiasis, kidney failure, cancer, and can even lead to death. So, development of a simple and low cost method for the detection of fluoride ions in water is highly desirable. In this study, a fluorometric method based on Ag-CdS/Ag-ZnS core/shell nanoparticles is developed for fluoride ion detection. The method was tested in aqueous solution at different pH values. The selectivity and sensitivity of the fluorescence probe was checked in the presence of other anions (Cl(-), Br(-), I(-), NO3(-) SO4(2-), HCO3(-), HPO4(2-), CH3COO(-), and H2PO4(-)) and found there is no significant interference of these associated ions. The fluoride ion concentration was varied in the range 190-22 800 μg L(-1) and a lower detection limit was obtained as 99.7 μg L(-1).

  7. Synthesis of a phenolic precursor and its efficient O-[18F]fluoroethylation with purified no-carrier-added [18F]2-fluoroethyl brosylate as the labeling agent.

    PubMed

    Jarkas, Nashwa; Voll, Ronald J; Goodman, Mark M

    2013-09-01

    [(18)F]2-Fluoroethyl-p-toluenesulfonate also called [(18)F]2-fluoroethyl tosylate has been widely used for labeling radioligands for positron emission tomography (PET). [(18)F]2-Fluoroethyl-4-bromobenzenesulfonate, also called [(18)F]2-fluoroethyl brosylate ([(18)F]F(CH2)2OBs), was used as an alternative radiolabeling agent to prepare [(18)F]FEOHOMADAM, a fluoroethoxy derivative of HOMADAM, by O-fluoroethylating the phenolic precursor. Purified by reverse-phase HPLC, the no-carrier-added [(18)F]F(CH2)2OBs was obtained in an average radiochemical yield (RCY) of 35%. The reaction of the purified and dried [(18)F]F(CH2)2OBs with the phenolic precursor was performed by heating in DMF and successfully produced [(18)F]FEOHOMADAM, after HPLC purification, in RCY of 21%.

  8. Chemical modification of the poly(vinylidene fluoride-trifluoroethylene) copolymer surface through fluorocarbon ion beam deposition

    SciTech Connect

    Hsu, W.-D.; Jang, Inkook; Sinnott, Susan B.

    2007-07-15

    Classical molecular dynamics simulations are used to study the effects of continuous fluorocarbon ion beam deposition on a poly(vinylidene fluoride-trifluoroethylene) [P(VDF-trFE)] surface, a polymer with electromechanical properties. Fluorocarbon plasma processing is widely used to chemically modify surfaces and deposit thin films. It is well accepted that polyatomic ions and neutrals within low-energy plasmas have a significant effect on the surface chemistry induced by the plasma. The deposition of mass selected fluorocarbon ions is useful to isolate the effects specific to polyatomic ions. Here, the differences in the chemical interactions of C{sub 3}F{sub 5}{sup +} and CF{sub 3}{sup +} ions with the P(VDF-trFE) surface are examined. The incident energy of the ions in both beams is 50 eV. The CF{sub 3}{sup +} ions are predicted to be more effective at fluorinating the P(VDF-trFE) surface than C{sub 3}F{sub 5}{sup +} ions. At the same time, the C{sub 3}F{sub 5}{sup +} ions are predicted to be more effective at growing fluorocarbon thin films. The simulations also reveal how the deposition process might ultimately modify the electromechanical properties of this polymer surface.

  9. Bridging the gaps in 18F PET tracer development

    NASA Astrophysics Data System (ADS)

    Campbell, Michael G.; Mercier, Joel; Genicot, Christophe; Gouverneur, Véronique; Hooker, Jacob M.; Ritter, Tobias

    2017-01-01

    As compared to the drug discovery process, the development of new 18F PET tracers lacks a well-established pipeline that advances compounds from academic research to candidacy for (pre)clinical imaging. In order to bridge the gaps between methodological advances and clinical success, we must rethink the development process from training to implementation.

  10. 17 CFR 270.18f-3 - Multiple class companies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Multiple class companies. 270... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.18f-3 Multiple class companies... registered open-end management investment company or series or class thereof established in accordance...

  11. 17 CFR 270.18f-3 - Multiple class companies.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Multiple class companies. 270... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.18f-3 Multiple class companies... registered open-end management investment company or series or class thereof established in accordance...

  12. 17 CFR 270.18f-3 - Multiple class companies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Multiple class companies. 270... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.18f-3 Multiple class companies... registered open-end management investment company or series or class thereof established in accordance...

  13. 17 CFR 270.18f-3 - Multiple class companies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Multiple class companies. 270... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.18f-3 Multiple class companies... registered open-end management investment company or series or class thereof established in accordance...

  14. 17 CFR 270.18f-3 - Multiple class companies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Multiple class companies. 270... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.18f-3 Multiple class companies... registered open-end management investment company or series or class thereof established in accordance...

  15. Carbon Nanohorns Carried Iron Fluoride Nanocomposite with ultrahigh rate lithium ion storage properties

    PubMed Central

    Fan, Lishuang; Li, Bingjiang; Zhang, Naiqing; Sun, Kening

    2015-01-01

    Novel hierarchical carbon nanohorns (CNHs) carried iron fluoride nanocomposites have been constructed by direct growth of FeF3·0.33H2O nanoparticles on CNHs. In the FeF3·0.33H2O@CNHs nanocomposite, the mesopore CNHs play the role as conductive matrix and robust carrier to support the FeF3·0.33H2O nanoparticles. The intimate conductive contact between the two components can build up an express way of electron transfer for rapid Li+ insertion/extraction. The CNHs can not only suppress the growth and agglomeration of FeF3·0.33H2O during the crystallization process, but also sever as an “elastic confinement” to support FeF3·0.33H2O. As was to be expected, the hierarchical FeF3·0.33H2O@CNHs nanocomposite exhibits impressive rate capability and excellent cycle performance. Markedly, the nanocomposite proves stable, ultrahigh rate lithium ion storage properties of 81 mAh g−1 at charge/discharge rate of 50 C (a discharge/charge process only takes 72 s). The integration of high electron conductivity, confined nano sized FeF3·0.33H2O (~5 nm), hierarchical mesopores CNHs and the “elastic confinement” support, the FeF3·0.33H2O@CNHs nanocomposite demonstrates excellent ultrahigh rate capability and good cycling properties. PMID:26173994

  16. Application of Palladium-Mediated 18F-Fluorination to PET Radiotracer Development: Overcoming Hurdles to Translation

    PubMed Central

    Kamlet, Adam S.; Neumann, Constanze N.; Lee, Eunsung; Carlin, Stephen M.; Moseley, Christian K.; Stephenson, Nickeisha; Hooker, Jacob M.; Ritter, Tobias

    2013-01-01

    New chemistry methods for the synthesis of radiolabeled small molecules have the potential to impact clinical positron emission tomography (PET) imaging, if they can be successfully translated. However, progression of modern reactions from the stage of synthetic chemistry development to the preparation of radiotracer doses ready for use in human PET imaging is challenging and rare. Here we describe the process of and the successful translation of a modern palladium-mediated fluorination reaction to non-human primate (NHP) baboon PET imaging–an important milestone on the path to human PET imaging. The method, which transforms [18F]fluoride into an electrophilic fluorination reagent, provides access to aryl–18F bonds that would be challenging to synthesize via conventional radiochemistry methods. PMID:23554994

  17. Application of palladium-mediated (18)F-fluorination to PET radiotracer development: overcoming hurdles to translation.

    PubMed

    Kamlet, Adam S; Neumann, Constanze N; Lee, Eunsung; Carlin, Stephen M; Moseley, Christian K; Stephenson, Nickeisha; Hooker, Jacob M; Ritter, Tobias

    2013-01-01

    New chemistry methods for the synthesis of radiolabeled small molecules have the potential to impact clinical positron emission tomography (PET) imaging, if they can be successfully translated. However, progression of modern reactions from the stage of synthetic chemistry development to the preparation of radiotracer doses ready for use in human PET imaging is challenging and rare. Here we describe the process of and the successful translation of a modern palladium-mediated fluorination reaction to non-human primate (NHP) baboon PET imaging-an important milestone on the path to human PET imaging. The method, which transforms [(18)F]fluoride into an electrophilic fluorination reagent, provides access to aryl-(18)F bonds that would be challenging to synthesize via conventional radiochemistry methods.

  18. 5 d-4 f luminescence of Nd3+, Gd3+, Er3+, Tm3+, and Ho3+ ions in crystals of alkaline earth fluorides

    NASA Astrophysics Data System (ADS)

    Radzhabov, E. A.; Prosekina, E. A.

    2011-09-01

    The vacuum ultraviolet emission spectra of alkaline-earth fluoride (CaF2, SrF2, BaF2) crystals with rare earth impurity ions (Nd, Gd, Er, Tm, Ho) have been investigated. The main luminescence bands are described well by the transitions from the lowest excited 5 d state to different 4 f levels of rare earth ions.

  19. 18F-fluorodeoxyglucose and 18F-flumazenil positron emission tomography in patients with refractory epilepsy

    PubMed Central

    Topakian, Raffi; Pichler, Robert

    2016-01-01

    Abstract Background Epilepsy is a neurological disorder characterized by epileptic seizures as a result of excessive neuronal activity in the brain. Approximately 65 million people worldwide suffer from epilepsy; 20–40% of them are refractory to medication therapy. Early detection of disease is crucial in the management of patients with epilepsy. Correct localization of the ictal onset zone is associated with a better surgical outcome. The modern non-invasive techniques used for structural-functional localization of the seizure focus includes electroencephalography (EEG) monitoring, magnetic resonance imaging (MRI), single photon emission tomography/computed tomography (SPECT/CT) and positron emission tomography/computed tomography (PET/CT). PET/CT can predict surgical outcome in patients with refractory epilepsy. The aim of the article is to review the current role of routinely used tracer 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) as well as non routinely used 18F-Flumazenil (18F-FMZ) tracers PET/CT in patients with refractory epilepsy. Conclusions Functional information delivered by PET and the morphologic information delivered by CT or MRI are essential in presurgical evaluation of epilepsy. Nowadays 18F-FDG PET/CT is a routinely performed imaging modality in localization of the ictal onset zone in patients with refractory epilepsy who are unresponsive to medication therapy. Unfortunately, 18F-FDG is not an ideal PET tracer regarding the management of patients with epilepsy: areas of glucose hypometabolism do not correlate precisely with the proven degree of change within hippocampal sclerosis, as observed by histopathology or MRI. Benzodiazepine-receptor imaging is a promising alternative in nuclear medicine imaging of epileptogenic focus. The use of 11C-FMZ in clinical practice has been limited by its short half-life and necessitating an on-site cyclotron for production. Therefore, 18F-FMZ might be established as one of the tracers of choice for patients

  20. Corrosion investigations on zircaloy-4 and titanium dissolver materials for MOX fuel dissolution in concentrated nitric acid containing fluoride ions

    NASA Astrophysics Data System (ADS)

    Jayaraj, J.; Krishnaveni, P.; Krishna, D. Nanda Gopala; Mallika, C.; Mudali, U. Kamachi

    2016-05-01

    Aqueous reprocessing of plutonium-rich mixed oxide fuels require fluoride as a dissolution catalyst in boiling nitric acid for an effective dissolution of the spent fuel. High corrosion rates were obtained for the candidate dissolver materials zircaloy-4 (Zr-4) and commercial pure titanium (CP-Ti grade 2) in boiling 11.5 M HNO3 + 0.05 M NaF. Complexing the fluoride ions either with Al(NO3)3 or ZrO(NO3)2 aided in decreasing the corrosion rates of Zr-4 and CP-Ti. From the obtained corrosion rates it is concluded that CP-Ti is a better dissolver material than Zr-4 for extended service life in boiling 11.5 M HNO3 + 0.05 M NaF, when complexed with 0.15 M ZrO(NO3)2. XPS analysis confirmed the presence of TiO2 and absence of fluoride on the surface of CP-Ti samples, indicating that effective complexation had occurred in solution leading to passivation of the metal and imparting high corrosion resistance.

  1. Reproducibility of Static and Dynamic 18F-FDG, 18F-FLT, and 18F-FMISO MicroPET Studies in a Murine Model of HER2+ Breast Cancer

    PubMed Central

    Whisenant, Jennifer G.; Peterson, Todd E.; Fluckiger, Jacob U.; Tantawy, Mohammed Noor; Ayers, Gregory D.; Yankeelov, Thomas E.

    2013-01-01

    Purpose The objective of this study is to determine the reproducibility of static 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG), 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT), and [18F]-fluoromisonidazole (18F-FMISO) microPET measurements, as well as kinetic parameters returned from analyses of dynamic 18F-FLT and 18F-FMISO data. Procedures HER2+ xenografts were established in nude mice. Dynamic data were acquired for 60 min, followed by a repeat injection and second scan 6 h later. Reproducibility was assessed for the percent-injected dose per gram (%ID/g) for each radiotracer, and with kinetic parameters (K1–k4, Ki) for 18F-FLT and 18F-FMISO. Results The value needed to reflect a change in tumor physiology is given by the 95 % confidence interval (CI), which is ±14, ±5, and ±6 % for 18F-FDG (n=12), 18F-FLT (n=11), and 18F-FMISO (n=11) %ID/g, respectively. Vd (=K1/k2), k3, and KFLT are the most reproducible 18F-FLT (n=9) kinetic parameters, with 95 % CIs of ±18, ±10, and ±18 %, respectively. Vd and KFMISO are the most reproducible 18F-FMISO kinetic parameters (n=7) with 95 % CIs of ±16 and ±14 %, respectively. Conclusions Percent-injected dose per gram measurements are reproducible and appropriate for detecting treatment-induced changes. Kinetic parameters have larger threshold values, but are potentially sufficiently reproducible to detect treatment response. PMID:22644988

  2. Origins of Large Voltage Hysteresis in High-Energy-Density Metal Fluoride Lithium-Ion Battery Conversion Electrodes.

    PubMed

    Li, Linsen; Jacobs, Ryan; Gao, Peng; Gan, Liyang; Wang, Feng; Morgan, Dane; Jin, Song

    2016-03-02

    Metal fluorides and oxides can store multiple lithium ions through conversion chemistry to enable high-energy-density lithium-ion batteries. However, their practical applications have been hindered by an unusually large voltage hysteresis between charge and discharge voltage profiles and the consequent low-energy efficiency (<80%). The physical origins of such hysteresis are rarely studied and poorly understood. Here we employ in situ X-ray absorption spectroscopy, transmission electron microscopy, density functional theory calculations, and galvanostatic intermittent titration technique to first correlate the voltage profile of iron fluoride (FeF3), a representative conversion electrode material, with evolution and spatial distribution of intermediate phases in the electrode. The results reveal that, contrary to conventional belief, the phase evolution in the electrode is symmetrical during discharge and charge. However, the spatial evolution of the electrochemically active phases, which is controlled by reaction kinetics, is different. We further propose that the voltage hysteresis in the FeF3 electrode is kinetic in nature. It is the result of ohmic voltage drop, reaction overpotential, and different spatial distributions of electrochemically active phases (i.e., compositional inhomogeneity). Therefore, the large hysteresis can be expected to be mitigated by rational design and optimization of material microstructure and electrode architecture to improve the energy efficiency of lithium-ion batteries based on conversion chemistry.

  3. Anthraimidazoledione Based Reversible and Reusable Selective Chemosensors for Fluoride Ion: Naked-Eye, Colorimetric and Fluorescence "ON-OFF".

    PubMed

    Bhattacharyya, Bhaswati; Kundu, Arijit; Guchhait, Nikhil; Dhara, Kaliprasanna

    2017-02-09

    Novel anthraimidazoledione-based compounds (1-3) are synthesized as selective colorimetric and fluorescent sensors for fluoride ion. The binding properties of the probes (1-3) are studied with different anions in acetonitrile solvent. Spectral red shifts in the absorption spectra and 'turn-off' emission are observed when fluoride is added to 1-3. The striking green to orange color change in the ambient light is thought to be due to the deprotonation of the N-H proton of the imidazole moiety of the probes by the basic F(-) ion. Interestingly, in all three cases the nonfluorescent probe-F(-) solutions, on treatment with copper perchlorate, show distinct color change from orange to golden yellow with resumption of fluorescence intensity. Furthermore, the reversibility of sensors (1-3) for the detection of F(-) ion is tested for four cycles indicating that "ON-OFF-ON" mechanism is operative. Test strip based on sensor 2 acts as a reusable cost-effective F(-) sensor.

  4. Fluoridated Water

    MedlinePlus

    ... Genetics Services Directory Cancer Prevention Overview Research Fluoridated Water On This Page What is fluoride, and where is it found? What is water fluoridation? When did water fluoridation begin in the ...

  5. Fluoridation Basics

    MedlinePlus

    ... Water Fluoridation Journal Articles for Community Water Fluoridation Water Fluoridation Basics Recommend on Facebook Tweet Share Compartir ... because of tooth decay. History of Fluoride in Water In the 1930s, scientists examined the relationship between ...

  6. PET neuroimaging studies of [18F]CABS13 in a double transgenic mouse model of Alzheimer’s disease and non-human primates

    PubMed Central

    Liang, Steven H.; Holland, Jason P.; Stephenson, Nickeisha A.; Kassenbrock, Alina; Rotstein, Benjamin H.; Daignault, Cory P.; Lewis, Rebecca; Collier, Lee; Hooker, Jacob M.; Vasdev, Neil

    2016-01-01

    Fluorine-18 labeled 2-fluoro-8-hydroxyquinoline ([18F]CABS13) is a promising positron emission tomography (PET) radiopharmaceutical based on a metal chelator developed to probe the “metal hypothesis of Alzheimer’s disease”. Herein, a practical radiosynthesis of [18F]CABS13 was achieved by radiofluorination followed by deprotection of an O-benzyloxymethyl group. Automated production and formulation of [18F]CABS13 resulted in 19 ± 5% uncorrected radiochemical yield, relative to starting [18F]fluoride, with ≥95% chemical and radiochemical purities, and high specific activity (>2.5 Ci/μmol) within 80 minutes. Temporal PET neuroimaging studies were carried out in female transgenic B6C3- Tg(APPswe,PSEN1dE9)85Dbo/J (APP/PS1) and age-matched wild-type (WT) B6C3F1/J control mice at 3, 7 and 10 months of age. [18F]CABS13 showed an overall higher uptake and retention of radioactivity in the central nervous system of APP/PS1 mice versus WT mice with increasing age. However, PET/magnetic resonance imaging in normal non-human primates revealed that the tracer had low uptake in the brain and rapid formation of a hydrophilic radiometabolite. Identification of more metabolically stable 18F-hydroxyquinolines that can be readily accessed by the radiochemical strategy presented herein is underway. PMID:25776827

  7. A Comparative Study of Noninvasive Hypoxia Imaging with 18F-Fluoroerythronitroimidazole and 18F-Fluoromisonidazole PET/CT in Patients with Lung Cancer

    PubMed Central

    Huang, Yong; Yu, Qingxi; Zhu, Shouhui; Wang, Suzhen; Zhao, Shuqiang; Hu, Xudong; Yu, Jinming; Yuan, Shuanghu

    2016-01-01

    Purpose This is a clinical study to compare noninvasive hypoxia imaging using 18F-fluoroerythronitroimidazole (18F-FETNIM) and 18F-fluoromisonidazole (18F-FMISO) positron emission tomography/computed tomography (PET/CT) in patients with inoperable stages III–IV lung cancer. Methods A total of forty-two patients with inoperable stages III–IV lung cancer underwent 18F-FETNIM PET/CT (n = 18) and 18F-FMISO PET/CT (n = 24) before chemo/radiation therapy. The standard uptake values (SUVs) of malignant and normal tissues depict 18F-FETNIM PET/CT and 18F-FMISO PET/CT uptake. Tumor-to-blood ratios (T/B) were used to quantify hypoxia. Results All patients with lung cancer underwent 18F-FETNIM PET/CT and 18F-FMISO PET/CT successfully. Compared to 18F-FMISO, 18F-FETNIM showed similar uptake in muscle, thyroid, spleen, pancreas, heart, lung and different uptake in blood, liver, and kidney. Significantly higher SUV and T/B ratio with 18F-FMISO (2.56±0.77, 1.98±0.54), as compared to 18F-FETNIM (2.12±0.56, 1.42±0.33) were seen in tumor, P = 0.022, <0.001. For the patients with different histopathological subtypes, no significant difference of SUV (or T/B ratio) was observed both in 18F-FMISO and 18F-FETNIM in tumor. A significantly different SUV (or T/B ratio) was detected between < = 2cm, 2~5cm, and >5cm groups in 18F-FMISO PET/CT, P = 0.015 (or P = 0.029), whereas no difference was detected in 18F-FMISO PET/CT, P = 0.446 (or P = 0.707). Both 18F-FETNIM and 18F-FMISO showed significantly higher SUVs (or T/B ratios) in stage IV than stage III, P = 0.021, 0.013 (or P = 0.032, 0.02). Conclusion 18F-FMISO showed significantly higher uptake than 18F-FETNIM in tumor/non-tumor ratio and might be a better hypoxia tracer in lung cancer. PMID:27322586

  8. No-carrier-added [.sup.18 F]-N-fluoroalkylspiroperidols

    DOEpatents

    Shiue, Chyng-Yann; Wolf, Alfred P.; Bai, Lan-Qin; Teng, Ren-Tui

    1989-01-01

    There is disclosed radioligands labeled with the position emitting radionuclide [.sup.18 F] suitable for dynamic study in living humans with position emission transaxial tomography. These new [.sup.18 F]-N-fluoroalkylspiroperidols, wherein the alkyl group contains from 2-6 carbon atoms, exhibit extremely high affinity for the dopamine receptors and provide enhanced uptake and retention in the brain concomitant with reduced radiation burden. These characteristics all combine to make these new radioligands useful for mapping dopamine receptors in normal and disease states in the living brain. Additionally, a new synthetic procedure for these radioligands as well as a new procedure for preparing the radiolabeled alkyl halide alkylating reagents are also disclosed.

  9. No-carrier-added (/sup 18/F)-N-methylspiroperidol

    DOEpatents

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

    1985-10-04

    The present invention is directed to the synthesis of a radioligand, labeled with a positron emitting radionuclide which is suitable for dynamic studies in humans using positron emission transaxial tomography. No-carrier-added (NCA) (/sup 18/F)-N-methylspiroperiodl is prepared from four different sustrates: p-nitrobenzonitrile, cyclopropyl p-nitrophenyl ketone, p-cyclopropanoyl-N,N,N-trimethylanilinium iodide and p-cyclopropanoyl-N,N,N-trimethylanilinium perchlorate. The process for the production of NCA (/sup 18/F)-N-methylspiroperidol is a nucleophilic aromatic substitution reaction. Furthermore, the compound of this invention is shown to be effective as a new drug of choice for in vivo examination of dopamine binding sites in a human brain. In particular, this drug is primarily useful in the noninvasive technique of positron emission transaxial tomography (PETT).

  10. Visualization of Fluoride Ions In Vivo Using a Gadolinium(III)-Coumarin Complex-Based Fluorescence/MRI Dual-Modal Probe

    PubMed Central

    Wang, Yue; Song, Renfeng; Feng, Huan; Guo, Ke; Meng, Qingtao; Chi, Haijun; Zhang, Run; Zhang, Zhiqiang

    2016-01-01

    A new Gadolinium(III)–coumarin complex, DO3A-Gd-CA, was designed and prepared as a dual-modal probe for simultaneous fluorescence and relaxivity responses to fluoride ions (F−) in aqueous media and mice. DO3A-Gd-CA was designed by using Gd(III) center as an MRI signal output unit and fluoride binding site, and the 4-(diethylamino)-coumarin-3-carboxylic acid (CA) as a fluorescence reporter. Upon the addition of fluoride ions to the solution of DO3A-Gd-CA, the liberation of the coordinated CA ligand led to a 5.7-fold fluorescence enhancement and a 75% increase in the longitudinal relaxivity (r1). The fluorescent detection limit for fluoride ions was determined to be 8 μM based on a 3σ/slope. The desirable features of the proposed DO3A-Gd-CA, such as high sensitivity and specificity, reliability at physiological pH and low cytotoxicity enable its application in visualization of fluoride ion in mice. The successful in vivo imaging indicates that DO3A-Gd-CA could be potentially used in biomedical diagnosis fields. PMID:27999298

  11. Direct observation of Nd{sup 3+} and Tm{sup 3+} ion distributions in oxy-fluoride glass ceramics containing PbF{sub 2} nanocrystals

    SciTech Connect

    Zhang, Jihong; Zhao, Zhiyong; Liu, Chao; Zhang, Gaoke; Zhao, Xiujian; Heo, Jong; Jiang, Yang

    2014-12-15

    Nd{sup 3+} and Tm{sup 3+}, doped oxy-fluoride glasses and glass ceramics were prepared by conventional melt-quenching and subsequent heat-treatment, respectively. β-PbF{sub 2} nanocrystals with diameter 50 –100 nm formed in the glass matrix after heat treatment. The Stark splitting in absorption peaks, enhanced photoluminescence and prolonged lifetimes that β-PbF{sub 2} nanocrystal formation increased the luminescence of rare earth ions. Both Nd{sup 3+} and Tm{sup 3+} ions were incorporated into nanocrystals that were enriched in lead and fluorine, and deficient in oxygen. - Highlights: • EELS analysis for rare-earth ion distribution in oxy-fluoride glass ceramics • No significant changes in lifetimes of Nd{sup 3+}, while obvious change for Tm{sup 3+} • Direct evidence of Nd{sup 3+} and Tm{sup 3+} aggregation into fluoride nanocrystals.

  12. Kinetic Modeling and Graphical Analysis of 18F-Fluoromethylcholine (FCho), 18F-Fluoroethyltyrosine (FET) and 18F-Fluorodeoxyglucose (FDG) PET for the Fiscrimination between High-Grade Glioma and Radiation Necrosis in Rats

    PubMed Central

    Lybaert, Kelly; Moerman, Lieselotte; Descamps, Benedicte; Deblaere, Karel; Boterberg, Tom; Kalala, Jean-Pierre; Van den Broecke, Caroline; De Vos, Filip; Vanhove, Christian; Goethals, Ingeborg

    2016-01-01

    Background Discrimination between glioblastoma (GB) and radiation necrosis (RN) post-irradiation remains challenging but has a large impact on further treatment and prognosis. In this study, the uptake mechanisms of 18F-fluorodeoxyglucose (18F-FDG), 18F-fluoroethyltyrosine (18F-FET) and 18F-fluoromethylcholine (18F-FCho) positron emission tomography (PET) tracers were investigated in a F98 GB and RN rat model applying kinetic modeling (KM) and graphical analysis (GA) to clarify our previous results. Methods Dynamic 18F-FDG (GB n = 6 and RN n = 5), 18F-FET (GB n = 5 and RN n = 5) and 18F-FCho PET (GB n = 5 and RN n = 5) were acquired with continuous arterial blood sampling. Arterial input function (AIF) corrections, KM and GA were performed. Results The influx rate (Ki) of 18F-FDG uptake described by a 2-compartmental model (CM) or using Patlak GA, showed more trapping (k3) in GB (0.07 min-1) compared to RN (0.04 min-1) (p = 0.017). K1 of 18F-FET was significantly higher in GB (0.06 ml/ccm/min) compared to RN (0.02 ml/ccm/min), quantified using a 1-CM and Logan GA (p = 0.036). 18F-FCho was rapidly oxidized complicating data interpretation. Using a 1-CM and Logan GA no clear differences were found to discriminate GB from RN. Conclusions Based on our results we concluded that using KM and GA both 18F-FDG and 18F-FET were able to discriminate GB from RN. Using a 2-CM model more trapping of 18F-FDG was found in GB compared to RN. Secondly, the influx of 18F-FET was higher in GB compared to RN using a 1-CM model. Important correlations were found between SUV and kinetic or graphical measures for 18F-FDG and 18F-FET. 18F-FCho PET did not allow discrimination between GB and RN. PMID:27559736

  13. CHARACTERIZATION OF TANK 18F WALL AND SCALE SAMPLES

    SciTech Connect

    Hay, Michael; Click, Damon; Diprete, c.; Diprete, David

    2010-03-01

    Samples from the wall of Tank 18F were obtained to determine the associated source term using a special wall sampling device. Two wall samples and a scale sample were obtained and characterized at the Savannah River National Laboratory (SRNL). All the analyses of the Tank 18F wall and scale samples met the targeted detection limits. The upper wall samples show {approx}2X to 6X higher concentrations for U, Pu, and Np on an activity per surface area basis than the lower wall samples. On an activity per mass basis, the upper and lower wall samples show similar compositions for U and Pu. The Np activity is still {approx}2.5X higher in the upper wall sample on a per mass basis. The scale sample contains 2-3X higher concentrations of U, Pu, and Sr-90 than the wall samples on an activity per mass basis. The plutonium isotopics differ for all three wall samples (upper, lower, and scale samples). The Pu-238 appears to increase as a proportion of total plutonium as you move up the tank wall from the lowest sample (scale sample) to the upper wall sample. The elemental composition of the scale sample appears similar to other F-Area PUREX sludge compositions. The composition of the scale sample is markedly different than the material on the floor of Tank 18F. However, the scale sample shows elevated Mg and Ca concentrations relative to typical PUREX sludge as do the floor samples.

  14. Pharmacokinetic evaluation of the tau PET radiotracer 18F-T807 (18F-AV-1451) in human subjects

    PubMed Central

    Wooten, Dustin W.; Guehl, Nicolas J.; Verwer, Eline E.; Shoup, Timothy M.; Yokell, Daniel L.; Zubcevik, Nevena; Vasdev, Neil; Zafonte, Ross D.; Johnson, Keith A.; Fakhri, Georges El; Normandin, Marc D.

    2017-01-01

    18F-T807 is a PET radiotracer developed for imaging tau protein aggregates, which are implicated in neurological disorders including Alzheimer's disease (AD) and traumatic brain injury (TBI). The current study characterizes 18F-T807 pharmacokinetics in human subjects using dynamic PET imaging and metabolite-corrected arterial input functions. Methods Nine subjects (4 control, 3 with history of TBI, 2 mild cognitive impairment (MCI) due to suspected AD) underwent dynamic PET imaging for up to 120 minutes after bolus injection of 18F-T807 with arterial blood sampling. Total volume of distribution (VT) was estimated using compartmental modeling (one- and two-tissue configurations) and graphical analysis techniques (Logan and MA1 regression methods). Reference region-based methods of quantification were explored including Logan distribution volume ratio (DVR) and static standardized uptake value ratio (SUVR) utilizing the cerebellum as a reference tissue. Results Percent unmetabolized 18F-T807 in plasma followed a single exponential with T1/2 of 17.0±4.2 minutes. Metabolite corrected plasma radioactivity concentration fit a bi-exponential (T1/2: 18.1±5.8; 2.4±0.5 minutes). 18F-T807 in gray matter peaked quickly (SUV >2 at ∼5 minutes). Compartmental modeling resulted in good fits and the two-tissue model with estimated blood volume correction (2Tv) performed best, particularly in regions with elevated binding. VT was greater in MCI subjects than controls in the occipital, parietal, and temporal cortices as well as the posterior cingulate gyrus, precuneus, and mesial temporal cortex. High focal uptake was found in the posterior corpus callosum of a TBI subject. Plots from Logan and MA1 graphical methods became linear by 30 minutes, yielding regional estimates of VT in excellent agreement with compartmental analysis and providing high quality parametric maps when applied in voxelwise fashion. Reference region based approaches including Logan DVR (t*=55 min) and SUVR

  15. Direct radiolabelling of proteins at cysteine using [18F]-fluorosugars.

    PubMed

    Boutureira, Omar; Bernardes, Gonçalo J L; D'Hooge, François; Davis, Benjamin G

    2011-09-28

    A strategy for the site-specific attachment of 2-deoxy-2-fluorosugars to cysteine and dehydroalanine tagged proteins is reported. When combined with thionation of fluorosugars, such as the widely available (18)F probe 2-deoxy-2-[(18)F]fluoroglucose ([(18)F]FDG), this methodology allows fast and direct access to site-specific [(18)F]FDG-labelled proteins.

  16. A fluoride-derived electrophilic late-stage fluorination reagent for PET imaging.

    PubMed

    Lee, Eunsung; Kamlet, Adam S; Powers, David C; Neumann, Constanze N; Boursalian, Gregory B; Furuya, Takeru; Choi, Daniel C; Hooker, Jacob M; Ritter, Tobias

    2011-11-04

    The unnatural isotope fluorine-18 ((18)F) is used as a positron emitter in molecular imaging. Currently, many potentially useful (18)F-labeled probe molecules are inaccessible for imaging because no fluorination chemistry is available to make them. The 110-minute half-life of (18)F requires rapid syntheses for which [(18)F]fluoride is the preferred source of fluorine because of its practical access and suitable isotope enrichment. However, conventional [(18)F]fluoride chemistry has been limited to nucleophilic fluorination reactions. We report the development of a palladium-based electrophilic fluorination reagent derived from fluoride and its application to the synthesis of aromatic (18)F-labeled molecules via late-stage fluorination. Late-stage fluorination enables the synthesis of conventionally unavailable positron emission tomography (PET) tracers for anticipated applications in pharmaceutical development as well as preclinical and clinical PET imaging.

  17. 18F-FDG super bone marrow uptake

    PubMed Central

    Alam, Mohammed Shah; Fu, Lilan; Ren, Yun-Yan; Wu, Hu-Bing; Wang, Quan-Shi; Han, Yan-Jiang; Zhou, Wen-Lan; Li, Hong-Sheng; Wang, Zhen

    2016-01-01

    Abstract The present study was performed to investigate whether the markedly 2-deoxy-2-(fluorine-18) fluoro-D-glucose (18F-FDG) uptake in the bone marrow (BM) is a presentation of malignant infiltration (MI). Super bone marrow uptake (super BMU) was used to name the markedly 18F-FDG uptake on BM, which was similar to or higher than that of the brain. From April 2008 to December 2015, 31 patients with such presentation were retrospectively reviewed. The 18F-FDG uptake was semiquantified using SUVmax and BM to cerebellum (BM/C) ratio. The origin of super BMU was diagnosed by pathology. Some blood parameters, as well as fever, were also collected and analyzed. For comparison, 106 patients with mildly and moderately uptake in BM and 20 healthy subjects were selected as the control group. Bone marrow MI was diagnosed in 93.5% (29/31) patients with super BMU, which mostly originated from acute leukemia and highly aggressive lymphoma. The super BMU group had markedly higher 18F-FDG uptake in the BM than those of mildly and moderately uptake, and the control subjects (all P = 0.000) and the BM/C ratio reached a high of 1.24 ± 0.36. The incidence of bone marrow MI in the super BMU group was markedly higher than that of mildly and moderately uptake (93.5% vs 36.8%, P = 0.000). Based on the receiver operating characteristic analysis, when cut-off values of BM/C and SUVmax were set at 0.835 and 6.560, the diagnostic specificity for bone marrow MI reached the high levels of 91.4% and 95.7%, respectively. In 15 patients with bone marrow MI, the extra-BM malignant lesions were simultaneously detected by 18F-FDG PET/CT. The liver and the nasal cavity involvements were only found in the patients with lymphoma, but not in those with leukemia. A decrease of leukocyte, hemoglobin, and platelet counts was noted in 48.4%, 86.2%, and 51.5% of patients with bone marrow MI, respectively. The present study revealed that super BMU was a highly potent indicator for the bone

  18. Fluoride ions as modifiers of the oxide layer produced by plasma electrolytic oxidation on AZ91D magnesium alloy

    NASA Astrophysics Data System (ADS)

    Kazanski, Barbara; Kossenko, Alexey; Zinigrad, Michael; Lugovskoy, Alex

    2013-12-01

    Plasma electrolytic oxidation (PEO) is a powerful technique allowing hardening and corrosion protection of valve metals due to formation of an oxide layer on the metal surface. PEO produces much thicker oxide layers as compared to anodizing, which is of critical importance for many technological applications. The present research investigated the influence of the fluoride ion concentration on the composition, structure and morphology of PEO layers on the magnesium alloy AZ91D. The obtained oxide layers were characterized with XRD, SEM, EDS and tested for corrosion resistance by linear sweep voltammetry in 3.5% NaCl medium. During this investigation it was found that KF addition produces significant changes in the structure and properties of the oxide layers. Fluorine was detected as an amorphous phase in the vicinity of the base metal for both alloys and plausible mechanism was suggested to explain these phenomena. Fluoride ions have pronounced catalytic activity and their presence considerably increases the thickness of the oxide layer. Depending on the process parameters, significant improvement of the corrosion stability of AZ91D alloy is achieved by the use of PEO.

  19. Fluoride coatings on orthodontic wire for controlled release of fluorine ion.

    PubMed

    Lee, Su-Hee; Kim, Hae-Won; Kong, Young-Min; Kim, Hyoun-Ee; Lee, Sung-Ho; Chang, Young-Il

    2005-10-01

    The purpose of this study was to develop a new method of releasing fluorine in a controlled manner for applications in the field of orthodontic Ti-based wire, namely the coating of fluorides on Ti. Thin films of two fluoride compounds, CaF(2) and MgF(2), were coated on Ti via the electron-beam evaporation method. The fluorine was released rapidly from the as-deposited MgF(2) coating within a short period(,) and then the release rate slowed down. When the MgF(2) coating was heat treated, this initial burst effect was decreased, but a significant amount of cracks were generated. On the other hand, in the case of the as-deposited CaF(2) coating, fluorine was released linearly for the entire period, without an initial burst. In the heat-treated CaF(2) coatings the trend was similarly observed. The linear fluorine release from the CaF(2) coatings, even in the as-deposited state, was attributed to the high degree of crystallinity of the coatings. A preliminary cell test showed favorable cell viability on both the fluoride coatings. Given their sustained and controlled fluorine release, these fluoride coatings, particularly CaF(2), are suggested to be potentially useful in the field of orthodontic Ti-based wire.

  20. One-Step Synthesis of Titanium Oxyhydroxy-Fluoride Rods and Research on the Electrochemical Performance for Lithium-ion Batteries and Sodium-ion Batteries.

    PubMed

    Li, Biao; Gao, Zhan; Wang, Dake; Hao, Qiaoyan; Wang, Yan; Wang, Yongkun; Tang, Kaibin

    2015-12-01

    Titanium oxyhydroxy-fluoride, TiO0.9(OH)0.9F1.2 · 0.59H2O rods with a hexagonal tungsten bronze (HTB) structure, was synthesized via a facile one-step solvothermal method. The structure, morphology, and component of the products were characterized by X-ray powder diffraction (XRD), thermogravimetry (TG), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution TEM (HRTEM), inductively coupled plasma optical emission spectroscopy (ICP-OES), ion chromatograph, energy-dispersive X-ray (EDX) analyses, and so on. Different rod morphologies which ranged from nanoscale to submicron scale were simply obtained by adjusting reaction conditions. With one-dimension channels for Li/Na intercalation/de-intercalation, the electrochemical performance of titanium oxyhydroxy-fluoride for both lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs) was also studied. Electrochemical tests revealed that, for LIBs, titanium oxyhydroxy-fluoride exhibited a stabilized reversible capacity of 200 mAh g(-1) at 25 mA g(-1) up to 120 cycles in the electrode potential range of 3.0-1.2 V and 140 mAh g(-1) at 250 mA g(-1) up to 500 cycles, especially; for SIBs, a high capacity of 100 mAh g(-1) was maintained at 25 mA g(-1) after 115 cycles in the potential range of 2.9-0.5 V.

  1. Improved and optimized one-pot method for N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB) synthesis using microwaves.

    PubMed

    Li, Kang-Po; Hu, Ming-Kuan; Kwang-Fu Shen, Clifton; Lin, Wei-Yu; Hou, Shuang; Zhao, Li-Bo; Cheng, Cheng-Yi; Shen, Daniel H

    2014-12-01

    N-Succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB) is a potential prosthetic agent for novel tracer development in positron emission tomography (PET). Previously, we reported a microwave-assisted one-pot synthesis of [(18)F]SFB with high efficacy. Herein, we reveal an improved and optimized approach based on this former model for producing [(18)F]SFB. With optimized approaches, the entire protocol can be completed within 25min, and [(18)F]SFB is generated in satisfactory quality for direct use without further purification via high-performance liquid chromatography.

  2. Fully automated synthesis of [(18) F]fluoro-dihydrotestosterone ([(18) F]FDHT) using the FlexLab module.

    PubMed

    Ackermann, Uwe; Lewis, Jason S; Young, Kenneth; Morris, Michael J; Weickhardt, Andrew; Davis, Ian D; Scott, Andrew M

    2016-08-01

    Imaging of androgen receptor expression in prostate cancer using F-18 FDHT is becoming increasingly popular. With the radiolabelling precursor now commercially available, developing a fully automated synthesis of [(18) F] FDHT is important. We have fully automated the synthesis of F-18 FDHT using the iPhase FlexLab module using only commercially available components. Total synthesis time was 90 min, radiochemical yields were 25-33% (n = 11). Radiochemical purity of the final formulation was > 99% and specific activity was > 18.5 GBq/µmol for all batches. This method can be up-scaled as desired, thus making it possible to study multiple patients in a day. Furthermore, our procedure uses 4 mg of precursor only and is therefore cost-effective. The synthesis has now been validated at Austin Health and is currently used for [(18) F]FDHT studies in patients. We believe that this method can easily adapted by other modules to further widen the availability of [(18) F]FDHT.

  3. Two dimensional fluoride ion conductor RbSn {2}F {5} studied by impedance spectroscopy and {19}F, {119}Sn, and {87}Rb NMR

    NASA Astrophysics Data System (ADS)

    Yamada, K.; Ahmad, M. M.; Ogiso, Y.; Okuda, T.; Chikami, J.; Miehe, G.; Ehrenberg, H.; Fuess, H.

    2004-07-01

    RbSn2F5 is a two-dimensional fluoride ion conductor. It undergoes a first-order phase transition to a superionic state at 368 K. The structure of the low temperature phase has been determined from the Rietveld analysis of the X-ray powder diffraction. The dynamic properties of the fluoride ions in RbSn2F5 have been studied by impedance spectroscopy and solid state NMR. The dc ionic conductivity of this sample shows an abrupt increase at the phase transition temperature. We have obtained the hopping frequency and the concentration of the charge carriers (F- ions) at different temperatures from the analysis of the conductivity spectra using Almond-West formalism. The estimated values of the charge carriers’ concentration agree well with that determined from the structure and were found to be independent of temperature. The relatively small value of the power-law exponent, n ≈ 0.55, supports the two-dimensional property of the investigated material. Furthermore, 19F NMR with simulation has suggested the diffusive motions of the fluoride ions between different sites. In contrast, 119Sn and 87Rb NMR spectra below 250 K supported the intrinsic disordered nature due to the random distribution of the fluoride ion vacancies.

  4. Stereotactic Comparison Study of 18F-Alfatide and 18F-FDG PET Imaging in an LLC Tumor-Bearing C57BL/6 Mouse Model

    PubMed Central

    Wei, Yu-Chun; Gao, Yongsheng; Zhang, Jianbo; Fu, Zheng; Zheng, Jinsong; Liu, Ning; Hu, Xudong; Hou, Wenhong; Yu, Jinming; Yuan, Shuanghu

    2016-01-01

    This study aimed to stereotactically compare the PET imaging performance of 18F-Alfatide (18F-ALF-NOTA-PRGD2, denoted as 18F-Alfatide) and 18F-fluorodeoxyglucose (FDG) and immunohistochemistry (IHC) staining in Lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mouse model. 18F-FDG standard uptake values (SUVs) were higher than 18F-Alfatide SUVs in tumors, most of the normal tissues and organs except for the bladder. Tumor-to-brain, tumor-to-lung, and tumor-to-heart ratios of 18F-Alfatide PET were significantly higher than those of 18F-FDG PET (P < 0.001). The spatial heterogeneity of the tumors was detected, and the tracer accumulation enhanced from the outer layer to the inner layer consistently using the two tracers. The parameters of the tumors were significantly correlated with each other between 18F-FDG SUV and GLUT-1 (R = 0.895, P < 0.001), 18F-Alfatide SUV and αvβ3 (R = 0.595, P = 0.019), 18F-FDG SUV and 18F-Alfatide SUV (R = 0.917, P < 0.001), and GLUT-1 and αvβ3 (R = 0.637, P = 0.011). Therefore, 18F-Alfatide PET may be an effective tracer for tumor detection, spatial heterogeneity imaging and an alternative supplement to 18F-FDG PET, particularly for patients with enhanced characteristics in the brain, chest tumors or diabetes, meriting further study. PMID:27350554

  5. Long-term quality assurance of [18F]-fluorodeoxyglucose (FDG) manufacturing

    PubMed Central

    Gaspar, Ludovit; Reich, Michal; Kassai, Zoltan; Macasek, Fedor; Rodrigo, Luis; Kruzliak, Peter; Kovac, Peter

    2016-01-01

    Nine years of experience with 2286 commercial synthesis allowed us to deliver comprehensive information on the quality of 18F-FDG production. Semi-automated FDG production line using Cyclone 18/9 machine (IBA Belgium), TRACERLab MXFDG synthesiser (GE Health, USA) using alkalic hydrolysis, grade “A” isolator with dispensing robotic unit (Tema Sinergie, Italy), and automatic control system under GAMP5 (minus2, Slovakia) was assessed by TQM tools as highly reliable aseptic production line, fully compliant with Good Manufacturing Practice and just-in-time delivery of FDG radiopharmaceutical. Fluoride-18 is received in steady yield and of very high radioactive purity. Synthesis yields exhibited high variance connected probably with quality of disposable cassettes and chemicals sets. Most performance non-conformities within the manufacturing cycle occur at mechanical nodes of dispensing unit. The long-term monitoring of 2286 commercial synthesis indicated high reliability of automatic synthesizers. Shewhart chart and ANOVA analysis showed that minor non-compliances occurred were mostly caused by the declinations of less experienced staff from standard operation procedures, and also by quality of automatic cassettes. Only 15 syntheses were found unfinished and in 4 cases the product was out-of-specification of European Pharmacopoeia. Most vulnerable step of manufacturing was dispensing and filling in grade “A” isolator. Its cleanliness and sterility was fully controlled under the investigated period by applying hydrogen peroxide vapours (VHP). Our experience with quality assurance in the production of [18F]-fluorodeoxyglucose (FDG) at production facility of BIONT based on TRACERlab MXFDG production module can be used for bench-marking of the emerging manufacturing and automated manufacturing systems. PMID:27508102

  6. Long-term quality assurance of [(18)F]-fluorodeoxyglucose (FDG) manufacturing.

    PubMed

    Gaspar, Ludovit; Reich, Michal; Kassai, Zoltan; Macasek, Fedor; Rodrigo, Luis; Kruzliak, Peter; Kovac, Peter

    2016-01-01

    Nine years of experience with 2286 commercial synthesis allowed us to deliver comprehensive information on the quality of (18)F-FDG production. Semi-automated FDG production line using Cyclone 18/9 machine (IBA Belgium), TRACERLab MXFDG synthesiser (GE Health, USA) using alkalic hydrolysis, grade "A" isolator with dispensing robotic unit (Tema Sinergie, Italy), and automatic control system under GAMP5 (minus2, Slovakia) was assessed by TQM tools as highly reliable aseptic production line, fully compliant with Good Manufacturing Practice and just-in-time delivery of FDG radiopharmaceutical. Fluoride-18 is received in steady yield and of very high radioactive purity. Synthesis yields exhibited high variance connected probably with quality of disposable cassettes and chemicals sets. Most performance non-conformities within the manufacturing cycle occur at mechanical nodes of dispensing unit. The long-term monitoring of 2286 commercial synthesis indicated high reliability of automatic synthesizers. Shewhart chart and ANOVA analysis showed that minor non-compliances occurred were mostly caused by the declinations of less experienced staff from standard operation procedures, and also by quality of automatic cassettes. Only 15 syntheses were found unfinished and in 4 cases the product was out-of-specification of European Pharmacopoeia. Most vulnerable step of manufacturing was dispensing and filling in grade "A" isolator. Its cleanliness and sterility was fully controlled under the investigated period by applying hydrogen peroxide vapours (VHP). Our experience with quality assurance in the production of [(18)F]-fluorodeoxyglucose (FDG) at production facility of BIONT based on TRACERlab MXFDG production module can be used for bench-marking of the emerging manufacturing and automated manufacturing systems.

  7. In Vivo Imaging with an αvβ6 Specific Peptide Radiolabeled using 18F-“Click” Chemistry: Evaluation and Comparison with the Corresponding 4-[18F]Fluorobenzoyl- and 2-[18F]Fluoropropionyl-Peptides

    PubMed Central

    Hausner, Sven H.; Marik, Jan; Gagnon, M. Karen J.; Sutcliffe, Julie L.

    2009-01-01

    Numerous radiolabeled peptides have been utilized for in vivo imaging of a variety of cell-surface receptors. For applications in PET using [18F]fluorine, peptides are radiolabeled via a prosthetic group approach. We previously developed solution-phase 18F-“click” radiolabeling and solid-phase radiolabeling using 4-[18F]fluorobenzoic and 2-[18F]fluoropropionic acids. Here we compare the 3 different radiolabeling approaches and report the effects on PET imaging and pharmacokinetics. The prosthetic groups did have an influence; metabolites with significantly different polarities were observed. PMID:18785727

  8. Radiosynthesis and preliminary PET evaluation of (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile for imaging AMPA receptors.

    PubMed

    Yuan, Gengyang; Jones, Graham B; Vasdev, Neil; Liang, Steven H

    2016-10-01

    To prompt the development of (18)F-labeled positron emission tomography (PET) tracers for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, we have prepared (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile ([(18)F]8). The radiosynthesis was achieved by a one-pot two-step method that utilized a spirocyclic hypervalent iodine(III) mediated radiofluorination to prepare the (18)F-labeled 1-bromo-3-fluorobenzene ([(18)F]15) intermediate with K(18)F. A subsequent copper(I) iodide mediated coupling reaction was carried out with 2-(2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile (10) to [(18)F]8 in 10±2% uncorrected radiochemical yield relative to starting (18)F-fluoride with >99% radiochemical purity and 29.6±7.4Gbq/μmol specific activity at the time of injection. PET imaging studies with the title radiotracer in normal mice demonstrated good brain uptake (peak standardized uptake value (SUV)=2.3±0.1) and warrants further in vivo validation.

  9. Optimization of the ion chromatographic quantification of airborne fluoride, acetate and formate in the Metropolitan Museum of Art, New York.

    PubMed

    Kontozova-Deutsch, Velichka; Deutsch, Felix; Bencs, László; Krata, Agnieszka; Van Grieken, René; De Wael, Karolien

    2011-10-30

    Ion chromatographic (IC) methods have been compared in order to achieve an optimal separation of fluoride, acetate and formate under various elution conditions on two formerly introduced analytical columns (i and ii) and a novel one (iii): (i) an IonPac AS14 (250 mm × 4 mm I.D.), (ii) Allsep A-2 (150 mm × 4.6mm I.D.), and (iii) an IC SI-50 4E (250 mm (length) × 4mm (internal diameter - I.D.)). The IC conditions for the separation of the anions concerned were optimized on the IC SI-50 4E column. A near baseline separation of these anions was attained on the IonPac AS14, whereas the peaks of fluoride and acetate could not be resolved on the Allsep A-2. A baseline separation for the three anions was achieved on the IC SI-50 4E column, when applying an eluent mixture of 3.2 mmol/L Na(2)CO(3) and 1.0 mmol/L NaHCO(3) with a flow rate of 1.0 mL/min. The highest precision of 1.7, 3.0 and 2.8% and the best limits of detection (LODs) of 0.014, 0.22 and 0.17 mg/L for fluoride, acetate and formate, respectively, were obtained with the IC SI-50 4E column. Hence, this column was applied for the determination of the acetic and formic acid contents of air samples taken by means of passive gaseous sampling at the Metropolitan Museum of Art in New York, USA. Atmospheric concentrations of acetic and formic acid up to 1050 and 450 μg/m(3), respectively, were found in non-aerated showcases of the museum. In galleries and outdoors, rather low levels of acetic and formic acid were detected with average concentrations of 50 and 10 μg/m(3), respectively. The LOD data of acetate and formate on the IC SI-50 4E column correspond to around 0.5 μg/m(3) for both acetic and formic acid in air samples.

  10. Mechanisms underlying 18F-fluorodeoxyglucose accumulation in colorectal cancer

    PubMed Central

    Kawada, Kenji; Iwamoto, Masayoshi; Sakai, Yoshiharu

    2016-01-01

    Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) is a diagnostic tool to evaluate metabolic activity by measuring accumulation of FDG, an analogue of glucose, and has been widely used for detecting small tumors, monitoring treatment response and predicting patients’ prognosis in a variety of cancers. However, the molecular mechanism of FDG accumulation into tumors remains to be investigated. It is well-known that most cancers are metabolically active with elevated glucose metabolism, a phenomenon known as the Warburg effect. The underlying mechanisms for elevated glucose metabolism in cancer tissues are complex. Recent reports have indicated the potential of FDG-PET/CT scans in predicting mutational status (e.g., KRAS gene mutation) of colorectal cancer (CRC), which suggests that FDG-PET/CT scans may play a key role in determining therapeutic strategies by non-invasively predicting treatment response to anti-epidermal growth factor receptor (EGFR) therapy. In this review, we summarize the current findings investigating the molecular mechanism of 18F-FDG accumulation in CRC. PMID:27928469

  11. [18F FDG PET-Applications in Oncology].

    PubMed

    Răileanu, Irena; Rusu, V; Stefănescu, Cipriana; Cinotti, L; Hountis, D

    2002-01-01

    In the first part our intention was, essentially, to present the particularities of glucose tumoral cells metabolism, PET components, the synthesis of 18F FDG and the detection of unknown cancers. This second part makes reference about mainly types of tumors who benefit by FDG-PET indications. Clinical PET has a rapid growth because of its use in cancer diagnosis and management. According with published studies all over the world, the sensibility and specificity of FDG-PET, noninvasive method, is higher than that of the conventional methods like CT, IRM, ultrasonography. PET is en excellent detection method of most of common cancer types and depends not on the histological neoplasm type; the more aggressive is the tumor, more it will uptake the radiotracer. The cost is significant, so the indications must be very precise: evaluating the malignity of solitary pulmonary nodules, evaluating the recurrences of melanoma, colon cancer diagnosis, differentiation between recurrent brain tumor and radiation injury, differential diagnosis of the benign lymph and malign lymph nodes, staging of Hodgkin's and non-Hodgkin's lymphoma, evaluation the response to therapy. Because the PET images are difficult to interpret, appears the necessity of correlation with anatomic images: this was the fusion images beginnings (the PET and CT images combination); now the physiologic information has precise anatomic localization. The growing of this method is very probably, both using 18F FDG -thanks to its highly favorable physical characteristics- and other new radiopharmaceuticals. The clinical cases that illustrate the applications are investigated at CERMEP, Lyon, France.

  12. Preparation and characterization of poly (arylene ether isoxazole)s by fluoride ion-mediated aromatic nucleophilic displacement reactions

    NASA Technical Reports Server (NTRS)

    Herbert, C. G.; Bass, R. G.

    1994-01-01

    As part of a continuing effort to prepare novel thermally stable high-performance polymers, poly(arylene ether isoxazole)s have been prepared by fluoride ion-catalyzed aromatic nucleophilic substitution reactions with bis(trimethylsiloxyphenyl) isoxazoles and activated bisarylhalides in diphenyl sulfone. Initial investigation involving the preparation of these materials with isoxazole bisphenols and activated bisarylhalides in the presence of potassium carbonate indicated that, under reaction conditions necessary to prepare high-molecular-weight materials, the isoxazole monomer was converted to an enamino ketone. This side reaction was avoided by using fluoride as a base. However, trimethylsilyl ether derivatives of the isoxazole bisphenols were required in these polymerizations for the preparation of high-molecular-weight materials. Moderate to high inherent viscosity eta(sub inh): 0.43-0.87 dl/g) materials with good thermal stability (air: 409-477 C, helium: 435-512 C) can be prepared by the silyl ether method. Glass transition temperatures ranged from 182 to 225 C for polymers with phenyl pendants and from 170 to 214 C for those without. Molecular weight control by 2% endcapping and the incorporation of a phenyl pendant at the 4 position of the isoxazole is necessary to yield polymers soluble in polar aprotic solvents at room temperature. There is evidence, however, indicating the existence of crosslinks between the polymer chains when the silyl ether approach is utilized.

  13. Sorption of doubly charged metal ions from ammonium fluoride solutions by KFP-23 cation-exchange resin

    SciTech Connect

    Ganyaev, V.P.; Pimneva, L.A.; Pakholkov, V.S.

    1982-10-20

    This report examines the results of a study of sorption of a number of doubly charged cations by the macroporous cation-exchange KFP-12 from 0.1 N MeF/sub 2/ solutions containing NH/sub 4/F in concentrations from 0 to 3.0 M. As the result of an investigation of the sorption, under dynamic conditions, of copper, zinc, cadmium, manganese, cobalt, and nickel ions from ammonium fluoride solutions by KFP-12 cation-exchange resin in the influence of the ionic form (H/sup +/ or NH/sub 4//sup +/) of the resin and of the NH/sub 4/F concentration on the degree of sorption and on the breakthrough capacity was established. The character of bonding and coordination of the sorbed cations with the ionic groups of the resin has been established. The possibilty of thorough purification of ammonium fluoride and (NH/sub 4/)/sub 2/BeF/sub 4/ solutions with the aid of KFP-12 resin in NH/sub 4//sup +/ form has been demonstrated. The purification co-efficients were calculated.

  14. Perspectives on Li and transition metal fluoride phosphates as cathode materials for a new generation of Li-ion batteries

    PubMed Central

    Antipov, Evgeny V.; Khasanova, Nellie R.; Fedotov, Stanislav S.

    2015-01-01

    To satisfy the needs of rapidly growing applications, Li-ion batteries require further significant improvements of their key properties: specific energy and power, cyclability, safety and costs. The first generation of cathode materials for Li-ion batteries based on mixed oxides with either spinel or rock-salt derivatives has already been widely commercialized, but the potential to improve the performance of these materials further is almost exhausted. Li and transition metal inorganic compounds containing different polyanions are now considered as the most promising cathode materials for the next generation of Li-ion batteries. Further advances in cathode materials are considered to lie in combining different anions [such as (XO4)n− and F−] in the anion sublattice, which is expected to enhance the specific energy and power of these materials. This review focuses on recent advances related to the new class of cathode materials for Li-ion batteries containing phosphate and fluoride anions. Special attention is given to their crystal structures and the relationships between structure and properties, which are important for their possible practical applications. PMID:25610630

  15. Perspectives on Li and transition metal fluoride phosphates as cathode materials for a new generation of Li-ion batteries.

    PubMed

    Antipov, Evgeny V; Khasanova, Nellie R; Fedotov, Stanislav S

    2015-01-01

    To satisfy the needs of rapidly growing applications, Li-ion batteries require further significant improvements of their key properties: specific energy and power, cyclability, safety and costs. The first generation of cathode materials for Li-ion batteries based on mixed oxides with either spinel or rock-salt derivatives has already been widely commercialized, but the potential to improve the performance of these materials further is almost exhausted. Li and transition metal inorganic compounds containing different polyanions are now considered as the most promising cathode materials for the next generation of Li-ion batteries. Further advances in cathode materials are considered to lie in combining different anions [such as (XO4) (n-) and F(-)] in the anion sublattice, which is expected to enhance the specific energy and power of these materials. This review focuses on recent advances related to the new class of cathode materials for Li-ion batteries containing phosphate and fluoride anions. Special attention is given to their crystal structures and the relationships between structure and properties, which are important for their possible practical applications.

  16. Preparation of 18F-labeled peptides using the copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition.

    PubMed

    Gill, Herman S; Marik, Jan

    2011-10-13

    An optimized procedure for preparing fluorine-18 ((18)F)-labeled peptides by the copper-catalyzed azide-alkyne 1,3-dipolar cyloaddition (CuAAC) is presented here. The two-step radiosynthesis begins with the microwave-assisted nucleophilic (18)F-fluorination of a precursor containing a terminal p-toluenesulfonyl, terminal azide and polyethylene glycol backbone. The resulting (18)F-fluorinated azide-containing building block is coupled to an alkyne-decorated peptide by the CuAAC. The reaction is accelerated by the copper(I)-stabilizing ligand bathophenanthroline disulfonate and can be performed in either reducing or nonreducing conditions (e.g., to preserve disulfide bonds). After an HPLC purification, (18)F-labeled peptide can be obtained with a 31 ± 6% radiochemical yield (n = 4, decay-corrected from (18)F-fluoride elution) and a specific activity of 39.0 ± 12.4 Ci μmol(-1) within 77 ± 4 min.

  17. (18)F-labeled positron emission tomographic radiopharmaceuticals in oncology: an overview of radiochemistry and mechanisms of tumor localization.

    PubMed

    Vallabhajosula, Shankar

    2007-11-01

    Molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in a living system. At present, positron emission tomography/computed tomography (PET/CT) is one the most rapidly growing areas of medical imaging, with many applications in the clinical management of patients with cancer. Although [(18)F]fluorodeoxyglucose (FDG)-PET/CT imaging provides high specificity and sensitivity in several kinds of cancer and has many applications, it is important to recognize that FDG is not a "specific" radiotracer for imaging malignant disease. Highly "tumor-specific" and "tumor cell signal-specific" PET radiopharmaceuticals are essential to meet the growing demand of radioisotope-based molecular imaging technology. In the last 15 years, many alternative PET tracers have been proposed and evaluated in preclinical and clinical studies to characterize the tumor biology more appropriately. The potential clinical utility of several (18)F-labeled radiotracers (eg, fluoride, FDOPA, FLT, FMISO, FES, and FCH) is being reviewed by several investigators in this issue. An overview of design and development of (18)F-labeled PET radiopharmaceuticals, radiochemistry, and mechanism(s) of tumor cell uptake and localization of radiotracers are presented here. The approval of clinical indications for FDG-PET in the year 2000 by the Food and Drug Administration, based on a review of literature, was a major breakthrough to the rapid incorporation of PET into nuclear medicine practice, particularly in oncology. Approval of a radiopharmaceutical typically involves submission of a "New Drug Application" by a manufacturer or a company clearly documenting 2 major aspects of the drug: (1) manufacturing of PET drug using current good manufacturing practices and (2) the safety and effectiveness of a drug with specific indications. The potential routine clinical utility of (18)F-labeled PET radiopharmaceuticals depends also on

  18. Comparability of [(18)F]THK5317 and [(11)C]PIB blood flow proxy images with [(18)F]FDG positron emission tomography in Alzheimer's disease.

    PubMed

    Rodriguez-Vieitez, Elena; Leuzy, Antoine; Chiotis, Konstantinos; Saint-Aubert, Laure; Wall, Anders; Nordberg, Agneta

    2017-02-01

    For amyloid positron emission tomography tracers, the simplified reference tissue model derived ratio of influx rate in target relative to reference region (R1) has been shown to serve as a marker of brain perfusion, and, due to the strong coupling between perfusion and metabolism, as a proxy for glucose metabolism. In the present study, 11 prodromal Alzheimer's disease and nine Alzheimer's disease dementia patients underwent [(18)F]THK5317, carbon-11 Pittsburgh Compound-B ([(11)C]PIB), and 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) positron emission tomography to assess the possible use of early-phase [(18)F]THK5317 and R1 as proxies for brain perfusion, and thus, for glucose metabolism. Discriminative performance (prodromal vs Alzheimer's disease dementia) of [(18)F]THK5317 (early-phase SUVr and R1) was compared with that of [(11)C]PIB (early-phase SUVr and R1) and [(18)F]FDG. Strong positive correlations were found between [(18)F]THK5317 (early-phase, R1) and [(18)F]FDG, particularly in frontal and temporoparietal regions. Differences in correlations between early-phase and R1 ([(18)F]THK5317 and [(11)C]PIB) and [(18)F]FDG, were not statistically significant, nor were differences in area under the curve values in the discriminative analysis. Our findings suggest that early-phase [(18)F]THK5317 and R1 provide information on brain perfusion, closely related to glucose metabolism. As such, a single positron emission tomography study with [(18)F]THK5317 may provide information about both tau pathology and brain perfusion in Alzheimer's disease, with potential clinical applications.

  19. Monitoring of anti-cancer treatment with (18)F-FDG and (18)F-FLT PET: a comprehensive review of pre-clinical studies.

    PubMed

    Jensen, Mette Munk; Kjaer, Andreas

    2015-01-01

    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 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 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. It is hypothesized that decreases in glycolysis and cell proliferation may occur in tumors that are sensitive to the applied cancer therapeutics and that tumors that are resistant to treatment will show unchanged glucose metabolism and cell proliferation. Whether (18)F-FDG and/or (18)F-FLT PET can be used for prediction of treatment response has been analyzed in many studies both following treatment with conventional chemotherapeutic agents but also following treatment with different targeted therapies, e.g. monoclonal antibodies and small molecules inhibitors. The results from these studies have been most variable; in some studies early changes in (18)F-FDG and (18)F-FLT uptake predicted later tumor regression whereas in other studies no change in tracer uptake was observed despite the treatment being effective. The present review gives an overview of pre-clinical studies that have used (18)F-FDG and/or (18)F-FLT PET for response monitoring of cancer therapeutics.

  20. Synthesis and bioevaluation of [18F]4-fluoro-m-hydroxyphenethylguanidine ([18F]4F-MHPG): a novel radiotracer for quantitative PET studies of cardiac sympathetic innervation

    PubMed Central

    Jang, Keun Sam; Jung, Yong-Woon; Sherman, Phillip S.; Quesada, Carole A.; Gu, Guie; Raffel, David M.

    2013-01-01

    A new cardiac sympathetic nerve imaging agent, [18F]4-fluoro-m-hydroxyphenethylguanidine ([18F]4F-MHPG), was synthesized and evaluated. The radiosynthetic intermediate [18F]4-fluoro-m-tyramine ([18F]4F-MTA) was prepared and then sequentially reacted with cyanogen bromide and NH4Br/NH4OH to afford [18F]4F-MHPG. Initial bioevaluations of [18F]4F-MHPG (biodistribution studies in rats and kinetic studies in the isolated rat heart) were similar to results previously reported for the carbon-11 labeled analog [11C]4F-MHPG. The neuronal uptake rate of [18F]4F-MHPG into the isolated rat heart was 0.68 ml/min/g wet and its retention time in sympathetic neurons was very long (T1/2 > 13 h). A PET imaging study in a nonhuman primate with [18F]4F-MHPG provided high quality images of the heart, with heart-to-blood ratios at 80–90 min after injection of 5-to-1. These initial kinetic and imaging studies of [18F]4F-MHPG suggest that this radiotracer may allow for more accurate quantification of regional cardiac sympathetic nerve density than is currently possible with existing neuronal imaging agents. PMID:23416009

  1. Eukaryotic resistance to fluoride toxicity mediated by a widespread family of fluoride export proteins.

    PubMed

    Li, Sanshu; Smith, Kathryn D; Davis, Jared H; Gordon, Patricia B; Breaker, Ronald R; Strobel, Scott A

    2013-11-19

    Fluorine is an abundant element and is toxic to organisms from bacteria to humans, but the mechanisms by which eukaryotes resist fluoride toxicity are unknown. The Escherichia coli gene crcB was recently shown to be regulated by a fluoride-responsive riboswitch, implicating it in fluoride response. There are >8,000 crcB homologs across all domains of life, indicating that it has an important role in biology. Here we demonstrate that eukaryotic homologs [renamed FEX (fluoride exporter)] function in fluoride export. FEX KOs in three eukaryotic model organisms, Neurospora crassa, Saccharomyces cerevisiae, and Candida albicans, are highly sensitized to fluoride (>200-fold) but not to other halides. Some of these KO strains are unable to grow in fluoride concentrations found in tap water. Using the radioactive isotope of fluoride, (18)F, we developed an assay to measure the intracellular fluoride concentration and show that the FEX deletion strains accumulate fluoride in excess of the external concentration, providing direct evidence of FEX function in fluoride efflux. In addition, they are more sensitive to lower pH in the presence of fluoride. These results demonstrate that eukaryotic FEX genes encode a previously unrecognized class of fluoride exporter necessary for survival in standard environmental conditions.

  2. 18F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance in Lymphoma

    PubMed Central

    Giraudo, Chiara; Raderer, Markus; Karanikas, Georgios; Weber, Michael; Kiesewetter, Barbara; Dolak, Werner; Simonitsch-Klupp, Ingrid; Mayerhoefer, Marius E.

    2016-01-01

    Objectives The aim of this study was to compare 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance (MR) (with and without diffusion-weighted imaging [DWI]) to 18F-FDG PET/computed tomography (CT), with regard to the assessment of nodal and extranodal involvement, in patients with Hodgkin lymphoma and non-Hodgkin lymphoma, without restriction to FDG-avid subytpes. Materials and Methods Patients with histologically proven lymphoma were enrolled in this prospective, institutional review board–approved study. After a single 18F-FDG injection, patients consecutively underwent 18F-FDG PET⁄CT and 18F-FDG PET/MR on the same day for staging or restaging. Three sets of images were analyzed separately: 18F-FDG PET/CT, 18F-FDG PET/MR without DWI, and 18F-FDG PET/MR with DWI. Region-based agreement and examination-based sensitivity and specificity were calculated for 18F-FDG PET/CT, 18F-FDG PET/MR without DWI, and 18F-FDG PET/MR DWI. Maximum and mean standardized uptake values (SUVmax, SUVmean) on 18F-FDG PET/CT and 18F-FDG PET/MR were compared and correlated with minimum and mean apparent diffusion coefficients (ADCmin, ADCmean). Results Thirty-four patients with a total of 40 examinations were included. Examination-based sensitivities for 18F-FDG PET/CT, 18F-FDG PET/MR, and 18F-FDG PET/MR DWI were 82.1%, 85.7%, and 100%, respectively; specificities were 100% for all 3 techniques; and accuracies were 87.5%, 90%, and 100%, respectively. 18F-FDG PET/CT was false negative in 5 of 40 examinations (all with mucosa-associated lymphoid tissue lymphoma), and 18F-FDG PET/MR (without DWI) was false negative in 4 of 40 examinations. Region-based percentages of agreement were 99% (κ, 0.95) between 18F-FDG PET/MR DWI and 18F-FDG PET/CT, 99.2% (κ, 0.96) between 18F-FDG PET/MR and 18F-FDG PET/CT, and 99.4% (κ, 0.97) between 18F-FDG PET/MR DWI and 18F-FDG PET/MR. There was a strong correlation between 18F-FDG PET/CT and 18F-FDG PET/MR for SUVmax (r = 0

  3. [Extension study and evaluation of the therapeutic response in a patient with metastatic lung adenocarcinoma using sequential study with ¹⁸F-FDG PET-CT and ¹⁸F-fluoride PET-CT].

    PubMed

    Moragas, M; Soler, M; Riera, E; García, J R

    2015-01-01

    We report a case of a patient with lung adenocarcinoma and bone and extraosseus metastases studied with (18)F-FDG PET-CT, (99m)Tc-HMDP and (18)F-fluoride PET-CT. It assesses the usefulness of (18)F-FDG PET-CT for initial staging of the disease and monitoring response to therapy. For the study of the sclerotic bone metastases it shows the superiority of 99mTc-HMDP bone scintigraphy and (18)F-fluoride PET-CT over (18)F-FDG PET-CT, and (18)F-fluoride PET-CT over bone scintigraphy. It also shows the usefulness of (18)F-fluoride PET-CT for monitoring the bone metastases.

  4. A new NIST primary standardization of 18F.

    PubMed

    Fitzgerald, R; Zimmerman, B E; Bergeron, D E; Cessna, J C; Pibida, L; Moreira, D S

    2014-02-01

    A new primary standardization of (18)F by NIST is reported. The standard is based on live-timed beta-gamma anticoincidence counting with confirmatory measurements by three other methods: (i) liquid scintillation (LS) counting using CIEMAT/NIST (3)H efficiency tracing; (ii) triple-to-double coincidence ratio (TDCR) counting; and (iii) NaI integral counting and HPGe γ-ray spectrometry. The results are reported as calibration factors for NIST-maintained ionization chambers (including some "dose calibrators"). The LS-based methods reveal evidence for cocktail instability for one LS cocktail. Using an ionization chamber to link this work with previous NIST results, the new value differs from the previous reports by about 4%, but appears to be in good agreement with the key comparison reference value (KCRV) of 2005.

  5. Optimal Fluoridation

    PubMed Central

    Lee, John R.

    1975-01-01

    Optimal fluoridation has been defined as that fluoride exposure which confers maximal cariostasis with minimal toxicity and its values have been previously determined to be 0.5 to 1 mg per day for infants and 1 to 1.5 mg per day for an average child. Total fluoride ingestion and urine excretion were studied in Marin County, California, children in 1973 before municipal water fluoridation. Results showed fluoride exposure to be higher than anticipated and fulfilled previously accepted criteria for optimal fluoridation. Present and future water fluoridation plans need to be reevaluated in light of total environmental fluoride exposure. PMID:1130041

  6. Interaction between nuclear graphite and molten fluoride salts: a synchrotron radiation study of the substitution of graphitic hydrogen by fluoride ion.

    PubMed

    Yang, Xinmei; Feng, Shanglei; Zhou, Xingtai; Xu, Hongjie; Sham, T K

    2012-01-26

    The interaction between nuclear graphite and molten fluoride salts (46.5 mol % LiF/11.5 mol % NaF/42 mol % KF) is investigated by synchrotron X-ray diffraction and C K-edge X-ray absorption near-edge structure (XANES). It is found that there are a large number of H atoms in IG-110 nuclear graphite, which is attributed to the residual C-H bond after the graphitization process of petroleum coke and pitch binder. The elastic recoil detection analysis indicates that H atoms are uniformly distributed in IG-110 nuclear graphite, in excellent agreement with the XANES results. The XANES results indicate that the immersion in molten fluoride salts at 500 °C led to H atoms in nuclear graphite partly substituted by the fluorine from fluoride salts to form C-F bond. The implications of these findings are discussed.

  7. Hopping rates and concentrations of mobile fluoride ions in Pb1-xSnxF2 solid solutions

    NASA Astrophysics Data System (ADS)

    Ahmad, Mohamad M.; Yamada, Koji

    2007-09-01

    In the present paper, the ion dynamics and relaxation of fluoride ions in Pb1-xSnxF2 (with x =0.2-0.6) solid solutions, prepared by mechanochemical milling, are studied in the conductivity formalism over wide ranges of frequencies and temperatures. The conductivity spectra of the investigated materials are analyzed by the Almond-West (AW) power-law model. The estimated values of the hopping rates and the dc conductivity of different compositions are thermally activated with almost the same activation energy. The calculated values of the concentration of mobile ions, nc, are almost independent of temperature and composition for x =0.2-0.4. The maximum value of nc is obtained for the x =0.6 sample, although it does not show the maximum conductivity. Therefore, the composition dependence of the ionic conductivity of these solid solutions could be explained based on the extracted parameters. The results presented in the current work indicate that the AW model represents a reasonable approximation of the overall frequency-dependent conductivity behavior of the investigated materials. The conductivity spectra at different temperatures for each composition are successfully scaled to a single master curve, indicating a temperature-independent relaxation mechanism. For different compositions, however, the conductivity spectra cannot be scaled properly, indicating composition-dependent relaxation dynamics.

  8. STATISTICAL ANALYSIS OF TANK 18F FLOOR SAMPLE RESULTS

    SciTech Connect

    Harris, S.

    2010-09-02

    Representative sampling has been completed for characterization of the residual material on the floor of Tank 18F as per the statistical sampling plan developed by Shine [1]. Samples from eight locations have been obtained from the tank floor and two of the samples were archived as a contingency. Six samples, referred to in this report as the current scrape samples, have been submitted to and analyzed by SRNL [2]. This report contains the statistical analysis of the floor sample analytical results to determine if further data are needed to reduce uncertainty. Included are comparisons with the prior Mantis samples results [3] to determine if they can be pooled with the current scrape samples to estimate the upper 95% confidence limits (UCL{sub 95%}) for concentration. Statistical analysis revealed that the Mantis and current scrape sample results are not compatible. Therefore, the Mantis sample results were not used to support the quantification of analytes in the residual material. Significant spatial variability among the current sample results was not found. Constituent concentrations were similar between the North and South hemispheres as well as between the inner and outer regions of the tank floor. The current scrape sample results from all six samples fall within their 3-sigma limits. In view of the results from numerous statistical tests, the data were pooled from all six current scrape samples. As such, an adequate sample size was provided for quantification of the residual material on the floor of Tank 18F. The uncertainty is quantified in this report by an upper 95% confidence limit (UCL{sub 95%}) on each analyte concentration. The uncertainty in analyte concentration was calculated as a function of the number of samples, the average, and the standard deviation of the analytical results. The UCL{sub 95%} was based entirely on the six current scrape sample results (each averaged across three analytical determinations).

  9. A Novel Method for Direct site-specific Radiolabeling of Peptides Using [18F]FDG

    PubMed Central

    Namavari, Mohammad; Cheng, Zhen; Zhang, Rong; De, Abhijit; Levi, Jelena; Hoerner, Joshua K.; Yaghoubi, Shahriar S.; Syud, Faisal A.; Gambhir, Sanjiv S.

    2009-01-01

    We have used the well-accepted and easily available 2-[18F]Fluoro-2-deoxyglucose ([18F]FDG) positron emission tomography (PET) tracer as a prosthetic group for synthesis of 18F-labeled peptides. We herein report the synthesis of [18F]FDG-RGD (18F labeled linear RGD) and [18F]FDG-cyclo(RGDDYK) (18F labeled cyclic RGD) as examples of the use of [18F]FDG. We have successfully prepared [18F]FDG-RGD and [18F]FDG-cyclo(RGDDYK) in 27.5% and 41% radiochemical yields (decay corrected) respectively. The receptor binding affinity study of FDG-cyclo(RGDDYK) for integrin αvβ3 , using αvβ3 positive U87MG cells confirmed a competitive displacement with 125I-echistatin as a radioligand. The IC50 value for FDG-cyclo(RGDDYK) was determined to be 0.67 ± 0.19µM. High contrast small animal PET images with relatively moderate tumor uptake were observed for [18F]FDG-RGD and [18F]FDG-cyclo(RGDDYK) as PET probes in xenografts models expressing αvβ3 integrin. In conclusion, we have successfully used [18F]FDG as a prosthetic group to prepare 18F]FDG-RGD and [18F]FDG-cyclic[RGDDYK] based on a simple one step radiosynthesis. The one step radiosynthesis methodology consists of chemoselective oxime formation between an aminooxy functionalized peptide and [18F]FDG. The results have implications for radiolabeling of other macromolecules and would lead to a very simple strategy for routine pre-clinical and clinical use. PMID:19226160

  10. Synthesis and Reactivity of (18)F-Labeled α,α-Difluoro-α-(aryloxy)acetic Acids.

    PubMed

    Khotavivattana, Tanatorn; Calderwood, Samuel; Verhoog, Stefan; Pfeifer, Lukas; Preshlock, Sean; Vasdev, Neil; Collier, Thomas L; Gouverneur, Véronique

    2017-02-03

    In this work, we describe the (18)F-labeling of α,α-difluoro-α-(aryloxy)acetic acid derivatives and demonstrate that these building blocks are amenable to post-(18)F-fluorination functionalization. Protodecarboxylation offers a new entry to (18)F-difluoromethoxyarene, and the value of this approach is further demonstrated with coupling processes leading to representative (18)F-labeled TRPV1 inhibitors and TRPV1 antagonists.

  11. Metabolites of 6-(/sup 18/F)fluoro-L-dopa in human blood

    SciTech Connect

    Firnau, G.; Sood, S.; Chirakal, R.; Nahmias, C.; Garnett, E.S.

    1988-03-01

    The metabolites of 6-(/sup 18/F)fluoro-L-dopa in the blood plasma of healthy humans have been identified as 3-O-sulfato-6(/sup 18/F)fluoro-L-dopa, 3-O-methyl-6-(/sup 18/F)fluoro-L-dopa, 6-(/sup 18/F) fluorodopamine, and 6-(/sup 18/F)fluorohomovanillic acid. The time course of these metabolites was followed up to 2 hr. The findings have implications for the use of 6-(/sup 18/F)fluoro-L-dopa as tracer for cerebral dopamine metabolism. Despite the variety of metabolites in the peripheral blood there are only two /sup 18/F-carrying compounds, 6-(/sup 18/F)fluoro-L-dopa and 3-O-methyl-6-(/sup 18/F)fluoro-L-dopa, that can cross the blood-brain barrier. After 1 hr, the plasma concentration of 3-O-methyl-6-(/sup 18/F)fluoro-L-dopa reaches approximately 20% that of 6-(/sup 18/F)fluoro-L-dopa but the mean concentration of the O-methylated metabolite over the same interval is less than 5% that of 6-(/sup 18/F)-fluoro-L-dopa.

  12. Longitudinal Characterization of [18F]-FDG and [18F]-AV45 Uptake in the Double Transgenic TASTPM Mouse Model

    PubMed Central

    Waldron, Ann-Marie; wyffels, Leonie; Verhaeghe, Jeroen; Richardson, Jill C.; Schmidt, Mark; Stroobants, Sigrid; Langlois, Xavier; Staelens, Steven

    2016-01-01

    We aimed to monitor the timing of amyloid-β deposition in relation to changes in brain function using in vivo imaging with [18F]-AV45 and [18F]-FDG in a mouse model of Alzheimer’s disease. TASTPM transgenic mice and wild-type controls were scanned longitudinally with [18F]-AV45 and [18F]-FDG before (3 months of age) and at multiple time points after the onset of amyloid deposition (6, 9, 12, and 15 months of age). As expected with increasing amyloidosis, TASTPM mice demonstrated progressive age-dependent increases in [18F]-AV45 uptake that were significantly higher than for WT from 9 months onwards and correlated to ex vivo measures of amyloid burden. The metabolism of [18F]-AV45 produces several brain penetrant radiometabolites and normalization to a reference region helps to negate this non-specific binding and improve the sensitivity of [18F]-AV45. The observed trajectory of [18F]-FDG alterations deviated from our proposed hypothesis of gradual decreases with worsening amyloidosis. While [18F]-FDG uptake in TASTPM mice was significantly lower than that of WT at 9 months, reduced [18F]-FDG was not associated with aging in TASTPM mice. Moreover, [18F]-FDG uptake did not correlate to measures of ex vivo amyloid burden. Our findings suggest that while amyloid-β is sufficient to induce hypometabolism, these pathologies are not linked in a dose-dependent manner in TASTPM mice. PMID:27911309

  13. A video-based tracking analysis to assess the chronic toxic effects of fluoride ion on the aquatic snail Potamopyrgus antipodarum (Hydrobiidae, Mollusca).

    PubMed

    Alonso, Álvaro; Camargo, Julio A

    2012-07-01

    Short-term lethal bioassays are not suited for assessing the real effects of pollutants in natural ecosystems, as their concentrations are usually unrealistic under an ecological point of view. By contrast, chronic bioassays are more realistic for assessing effects on aquatic animals, especially when behavioural endpoints are used. These endpoints are a good link between physiological and ecological effects. Among behavioural bioassays, those based on automated image analysis following video-recording have the advantage of being quantitative and non-subjective tests. The present study focuses on the assessment of chronic (63 days) effects of fluoride ion (F⁻) on the survival, proportion of affected animals (dead plus immobile animals) and several behavioural endpoints (monitored by video-recording and image analysis system) of the aquatic snail Potamopyrgus antipodarum (Hydrobiidae, Mollusca). The bioassay consisted of one control and three actual fluoride concentrations (4.68, 18.6, and 37.1 mg F⁻/L) with 12 replicates in each treatment. The endpoints were monitored every 7 day of continuous exposure to fluoride ion. The highest fluoride concentrations killed all animals at the end of the bioassay. By contrast no animals died in the lowest fluoride treatment, but snails showed several alterations of behaviour: increase heterogeneity of velocity among successive recording periods, increase of the time to escape from a marked circle, and reduction of the heterogeneity in the utilization of space. Therefore, most of the behavioural endpoints were sensitive to environmentally realistic non-lethal fluoride concentrations, being useful parameters for ecological risk assessment. The ecological relevance of these findings is discussed.

  14. [18F]- and [11C]-Labeled N-benzyl-isatin sulfonamide analogues as PET tracers for apoptosis: synthesis, radiolabeling mechanism, and in vivo imaging of apoptosis in Fas-treated mice

    PubMed Central

    Zhou, Dong; Chu, Wenhua; Chen, Delphine L.; Wang, Qi; Reichert, David E.; Rothfuss, Justin; D'Avignon, Andre; Welch, Michael J.; Mach, Robert H.

    2011-01-01

    Summary The radiolabeled isatin sulfonamide caspase-3 inhibitor, [18F]2 (WC-II-89), is a potential PET radiotracer for noninvasive imaging of apoptosis. The radiolabeling mechanism was studied by 13C NMR, ESI/MS, and computational calculations. It was found that the high electrophilicity of the C3 carbonyl group in the isatin ring, which served as a trap for [18F]fluoride, was responsible for the failure of the radiolabeling via nucleophilic substitution of the mesylate group in 7a by [18F]fluoride. Once treated with a strong base, 7a opened the isatin ring completely to form an isatinate intermediate 16, which lost the ability to trap [18F]fluoride, thereby allowing the displacement of the mesylate group to afford the 18F-labeled isatinate 17. [18F]17 can be converted to isatin [18F]2 efficiently under acidic conditions. The ring-opening and re-closure of the isatin ring under basic and acidic conditions were confirmed by reversed phase HPLC analysis, ESI/MS and 13C NMR studies. Computational studies of model compounds also support the above proposed mechanism. Similarly, the ring-opening and re-closure method was used successfully in the synthesis of the 11C labeled isatin sulfonamide analogue [11C]4 (WC-98). A microPET imaging study using [11C]4 in the Fas liver apoptosis model demonstrated retained activity in the target organ (liver) of the treated mice. Increased caspase-3 activation in the liver was verified by the fluorometric caspase-3 enzyme assay. Therefore, this study provides a useful method for radio-synthesis of isatin derivative radiotracers for PET and SPECT studies, and [11C]4 is a potential PET radiotracer for noninvasive imaging of apoptosis. PMID:19300818

  15. Effect of Fluoride Ions on the Anodic Behavior of Mill Annealed and Aged Alloy 22

    SciTech Connect

    Rodriguez, M A; Carranza-, R M; Rebak, R B

    2003-10-07

    Alloy 22 (N06022) is the current candidate alloy to fabricate the external wall of the high level nuclear waste containers for the Yucca Mountain repository. It was of interest to study and compare the general and localized corrosion susceptibility of Alloy 22 in saturated NaF solutions ({approx} 1 M NaF) at 90 C. Standard electrochemical tests such as cyclic potentiodynamic polarization, amperometry, potentiometry, and electrochemical impedance spectroscopy were used. Studied variables included the solution pH and the alloy microstructure (thermal aging). Results show that Alloy 22 is highly resistant to general and localized corrosion in pure fluoride solutions. Thermal aging is not detrimental and even seems to be slightly beneficial for general corrosion in alkaline solutions.

  16. Aqueous Glycosylation of Unprotected Sucrose Employing Glycosyl Fluorides in the Presence of Calcium Ion and Trimethylamine

    PubMed Central

    Pelletier, Guillaume; Zwicker, Aaron; Allen, C. Liana; Schepartz, Alanna; Miller, Scott J.

    2016-01-01

    We report a synthetic glycosylation reaction between sucrosyl acceptors and glycosyl fluoride donors to yield the derived trisaccharides. This reaction proceeds at room temperature in an aqueous solvent mixture. Calcium salts and a tertiary amine base promote the reaction with high site-selectivity for either the 3′-position or 1′-position of the fructofuranoside unit. Because non-enzymatic aqueous oligosaccharide syntheses are underdeveloped, mechanistic studies were carried out in order to identify the origin of the selectivity, which we hypothesized was related to the structure of hydroxyl group array in sucrose. The solution conformation of various mono-deoxysucrose analogs revealed the cooperative nature of the hydroxyl group in mediating both this aqueous glycosyl bond-forming reaction and the site-selectivity at the same time. PMID:26859619

  17. Bifunctional colorimetric chemosensing of fluoride and cyanide ions by nickel-POCOP pincer receptors.

    PubMed

    Salomón-Flores, María K; Bazany-Rodríguez, Iván J; Martínez-Otero, Diego; García-Eleno, Marco A; Guerra-García, Jorge J; Morales-Morales, David; Dorazco-González, Alejandro

    2017-03-08

    Three Ni(ii)-POCOP pincer complexes [NiCl{C6H2-4-OH-2,6-(OPPh2)2}], 1; [NiCl{C6H2-4-OH-2,6-(OPtBu2)2}], 2 and [NiCl{C6H2-4-OH-2,6-(OPiPr2)2}], 3 were studied as bifunctional molecular sensors for inorganic anions and acetate. In CH3CN, fluoride generates a bathochromic shift with a colorimetric change for 1-3 with a simultaneous fluorescence turn on, this optical effect is based on deprotonation of the para-hydroxy group of the POCOP ligand. On the other hand, in a neutral aqueous solution of 80 vol% CH3CN, additions of cyanide produce a distinct change of color by forming very stable complexes with the nickel-based receptors 1-3 with log Ka in the range of 4.38-5.03 M(-1) and pronounced selectivity over other common anions such as iodide, phosphate, and acetate. Additionally, bromide shows a modest spectral change and affinity, but lower than those observed for cyanide. On the basis of (1)H NMR experiments, UV-vis titrations, ESI-MS experiments, and the crystal structure of the neutral bromo complex of 1, it is proposed that the colorimetric change involves an exchange of chloride by CN(-) on the Ni(ii) atom. The Ni(ii)-based sensor 1 allows the fluorescent selective detection of fluoride with a limit of 5.66 μmol L(-1) and colorimetric sensing of cyanide in aqueous medium in the micromolar concentration range.

  18. 18F-Labelled Intermediates for Radiosynthesis by Modular Build-Up Reactions: Newer Developments

    PubMed Central

    Ermert, Johannes

    2014-01-01

    This brief review gives an overview of newer developments in 18F-chemistry with the focus on small 18F-labelled molecules as intermediates for modular build-up syntheses. The short half-life (<2 h) of the radionuclide requires efficient syntheses of these intermediates considering that multistep syntheses are often time consuming and characterized by a loss of yield in each reaction step. Recent examples of improved synthesis of 18F-labelled intermediates show new possibilities for no-carrier-added ring-fluorinated arenes, novel intermediates for tri[18F]fluoromethylation reactions, and 18F-fluorovinylation methods. PMID:25343144

  19. A Comparative Study of the Hypoxia PET Tracers [{sup 18}F]HX4, [{sup 18}F]FAZA, and [{sup 18}F]FMISO in a Preclinical Tumor Model

    SciTech Connect

    Peeters, Sarah G.J.A.; Zegers, Catharina M.L.; Lieuwes, Natasja G.; Elmpt, Wouter van; Eriksson, Jonas; Dongen, Guus A.M.S. van; Dubois, Ludwig; Lambin, Philippe

    2015-02-01

    Purpose: Several individual clinical and preclinical studies have shown the possibility of evaluating tumor hypoxia by using noninvasive positron emission tomography (PET). The current study compared 3 hypoxia PET tracers frequently used in the clinic, [{sup 18}F]FMISO, [{sup 18}F]FAZA, and [{sup 18}F]HX4, in a preclinical tumor model. Tracer uptake was evaluated for the optimal time point for imaging, tumor-to-blood ratios (TBR), spatial reproducibility, and sensitivity to oxygen modification. Methods and Materials: PET/computed tomography (CT) images of rhabdomyosarcoma R1-bearing WAG/Rij rats were acquired at multiple time points post injection (p.i.) with one of the hypoxia tracers. TBR values were calculated, and reproducibility was investigated by voxel-to-voxel analysis, represented as correlation coefficients (R) or Dice similarity coefficient of the high-uptake volume. Tumor oxygen modifications were induced by exposure to either carbogen/nicotinamide treatment or 7% oxygen breathing. Results: TBR was stabilized and maximal at 2 hours p.i. for [{sup 18}F]FAZA (4.0 ± 0.5) and at 3 hours p.i. for [{sup 18}F]HX4 (7.2 ± 0.7), whereas [{sup 18}F]FMISO showed a constant increasing TBR (9.0 ± 0.8 at 6 hours p.i.). High spatial reproducibility was observed by voxel-to-voxel comparisons and Dice similarity coefficient calculations on the 30% highest uptake volume for both [{sup 18}F]FMISO (R = 0.86; Dice coefficient = 0.76) and [{sup 18}F]HX4 (R = 0.76; Dice coefficient = 0.70), whereas [{sup 18}F]FAZA was less reproducible (R = 0.52; Dice coefficient = 0.49). Modifying the hypoxic fraction resulted in enhanced mean standardized uptake values for both [{sup 18}F]HX4 and [{sup 18}F]FAZA upon 7% oxygen breathing. Only [{sup 18}F]FMISO uptake was found to be reversible upon exposure to nicotinamide and carbogen. Conclusions: This study indicates that each tracer has its own strengths and, depending on the question to be answered, a different tracer can be put

  20. Improved synthesis of [(18)F]FLETT via a fully automated vacuum distillation method for [(18)F]2-fluoroethyl azide purification.

    PubMed

    Ackermann, Uwe; Plougastel, Lucie; Goh, Yit Wooi; Yeoh, Shinn Dee; Scott, Andrew M

    2014-12-01

    The synthesis of [(18)F]2-fluoroethyl azide and its subsequent click reaction with 5-ethynyl-2'-deoxyuridine (EDU) to form [(18)F]FLETT was performed using an iPhase FlexLab module. The implementation of a vacuum distillation method afforded [(18)F]2-fluoroethyl azide in 87±5.3% radiochemical yield. The use of Cu(CH3CN)4PF6 and TBTA as catalyst enabled us to fully automate the [(18)F]FLETT synthesis without the need for the operator to enter the radiation field. [(18)F]FLETT was produced in higher overall yield (41.3±6.5%) and shorter synthesis time (67min) than with our previously reported manual method (32.5±2.5% in 130min).

  1. Simultaneous determination of fluoride, chloride, sulfate, phosphate, monofluorophosphate, glycerophosphate, sorbate, and saccharin in gargles by ion chromatography.

    PubMed

    Zhang, Yan-zhen; Zhou, Yan-chun; Liu, Li; Zhu, Yan

    2007-07-01

    Simple, reliable and sensitive analytical methods to determine anticariogenic agents, preservatives, and artificial sweeteners contained in commercial gargles are necessary for evaluating their effectiveness, safety, and quality. An ion chromatography (IC) method has been described to analyze simultaneously eight anions including fluoride, chloride, sulfate, phosphate, monofluorophosphate, glycerophosphate (anticariogenic agents), sorbate (a preservative), and saccharin (an artificial sweetener) in gargles. In this IC system, we applied a mobile phased gradient elution with KOH, separation by IonPac AS18 columns, and suppressed conductivity detection. Optimized analytical conditions were further evaluated for accuracy. The relative standard deviations (RSDs) of the inter-day's retention time and peak area of all species were less than 0.938% and 8.731%, respectively, while RSDs of 5-day retention time and peak area were less than 1.265% and 8.934%, respectively. The correlation coefficients for targeted analytes ranged from 0.999 7 to 1.000 0. The spiked recoveries for the anions were 90% approximately 102.5%. We concluded that the method can be applied for comprehensive evaluation of commercial gargles.

  2. Novel polyvinylidene fluoride nanofiltration membrane blended with functionalized halloysite nanotubes for dye and heavy metal ions removal.

    PubMed

    Zeng, Guangyong; He, Yi; Zhan, Yingqing; Zhang, Lei; Pan, Yang; Zhang, Chunli; Yu, Zongxue

    2016-11-05

    Membrane separation is an effective method for the removal of hazardous materials from wastewater. Halloysite nanotubes (HNTs) were functionalized with 3-aminopropyltriethoxysilane (APTES), and novel polyvinylidene fluoride (PVDF) nanofiltration membranes were prepared by blending with various concentrations of APTES grafted HNTs (A-HNTs). The morphology structure of the membranes were characterized by scanning electron microscope (SEM) and atomic force microscopy (AFM). The contact angle (CA), pure water flux (PWF) and antifouling capacity of membranes were investigated in detail. In addition, the separation performance of membranes were reflected by the removal of dye and heavy metal ions in simulated wastewater. The results revealed that the hydrophilicity of A-HNTs blended PVDF membrane (A-HNTs@PVDF) was enhanced significantly. Owing to the electrostatic interaction between membrane surface and dye molecules, the dye rejection ratio of 3% A-HNTs@PVDF membrane reached 94.9%. The heavy metal ions rejection ratio and adsorption capacity of membrane were also improved with the addition of A-HNTs. More importantly, A-HNTs@PVDF membrane exhibited excellent rejection stability and reuse performances after several times fouling and washing tests. It can be expected that the present work will provide insight into a new method for membrane modification in the field of wastewater treatment.

  3. Conductivity degradation of polyvinylidene fluoride composite binder during cycling: Measurements and simulations for lithium-ion batteries

    SciTech Connect

    Grillet, Anne M.; Humplik, Thomas; Stirrup, Emily K.; Roberts, Scott A.; Barringer, David A.; Snyder, Chelsea M.; Janvrin, Madison R.; Apblett, Christopher A.

    2016-07-02

    The polymer-composite binder used in lithium-ion battery electrodes must both hold the electrodes together and augment their electrical conductivity while subjected to mechanical stresses caused by active material volume changes due to lithiation and delithiation. We have discovered that cyclic mechanical stresses cause significant degradation in the binder electrical conductivity. After just 160 mechanical cycles, the conductivity of polyvinylidene fluoride (PVDF):carbon black binder dropped between 45–75%. This degradation in binder conductivity has been shown to be quite general, occurring over a range of carbon black concentrations, with and without absorbed electrolyte solvent and for different polymer manufacturers. Mechanical cycling of lithium cobalt oxide (LiCoO2) cathodes caused a similar degradation, reducing the effective electrical conductivity by 30–40%. Mesoscale simulations on a reconstructed experimental cathode geometry predicted the binder conductivity degradation will have a proportional impact on cathode electrical conductivity, in qualitative agreement with the experimental measurements. Lastly, ohmic resistance measurements were made on complete batteries. Direct comparisons between electrochemical cycling and mechanical cycling show consistent trends in the conductivity decline. This evidence supports a new mechanism for performance decline of rechargeable lithium-ion batteries during operation – electrochemically-induced mechanical stresses that degrade binder conductivity, increasing the internal resistance of the battery with cycling.

  4. Conductivity degradation of polyvinylidene fluoride composite binder during cycling: Measurements and simulations for lithium-ion batteries

    DOE PAGES

    Grillet, Anne M.; Humplik, Thomas; Stirrup, Emily K.; ...

    2016-07-02

    The polymer-composite binder used in lithium-ion battery electrodes must both hold the electrodes together and augment their electrical conductivity while subjected to mechanical stresses caused by active material volume changes due to lithiation and delithiation. We have discovered that cyclic mechanical stresses cause significant degradation in the binder electrical conductivity. After just 160 mechanical cycles, the conductivity of polyvinylidene fluoride (PVDF):carbon black binder dropped between 45–75%. This degradation in binder conductivity has been shown to be quite general, occurring over a range of carbon black concentrations, with and without absorbed electrolyte solvent and for different polymer manufacturers. Mechanical cycling ofmore » lithium cobalt oxide (LiCoO2) cathodes caused a similar degradation, reducing the effective electrical conductivity by 30–40%. Mesoscale simulations on a reconstructed experimental cathode geometry predicted the binder conductivity degradation will have a proportional impact on cathode electrical conductivity, in qualitative agreement with the experimental measurements. Lastly, ohmic resistance measurements were made on complete batteries. Direct comparisons between electrochemical cycling and mechanical cycling show consistent trends in the conductivity decline. This evidence supports a new mechanism for performance decline of rechargeable lithium-ion batteries during operation – electrochemically-induced mechanical stresses that degrade binder conductivity, increasing the internal resistance of the battery with cycling.« less

  5. Preclinical Applications of 3'-Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic Review

    PubMed Central

    Schelhaas, Sonja; Heinzmann, Kathrin; Bollineni, Vikram R.; Kramer, Gerbrand M.; Liu, Yan; Waterton, John C.; Aboagye, Eric O.; Shields, Anthony F.; Soloviev, Dmitry; Jacobs, Andreas H.

    2017-01-01

    The positron emission tomography (PET) tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) has been proposed to measure cell proliferation non-invasively in vivo. Hence, it should provide valuable information for response assessment to tumor therapies. To date, [18F]FLT uptake has found limited use as a response biomarker in clinical trials in part because a better understanding is needed of the determinants of [18F]FLT uptake and therapy-induced changes of its retention in the tumor. In this systematic review of preclinical [18F]FLT studies, comprising 174 reports, we identify the factors governing [18F]FLT uptake in tumors, among which thymidine kinase 1 plays a primary role. The majority of publications (83 %) report that decreased [18F]FLT uptake reflects the effects of anticancer therapies. 144 times [18F]FLT uptake was related to changes in proliferation as determined by ex vivo analyses. Of these approaches, 77 % describe a positive relation, implying a good concordance of tracer accumulation and tumor biology. These preclinical data indicate that [18F]FLT uptake holds promise as an imaging biomarker for response assessment in clinical studies. Understanding of the parameters which influence cellular [18F]FLT uptake and retention as well as the mechanism of changes induced by therapy is essential for successful implementation of this PET tracer. Hence, our systematic review provides the background for the use of [18F]FLT in future clinical studies. PMID:28042315

  6. Systemic fluoride.

    PubMed

    Sampaio, Fábio Correia; Levy, Steven Marc

    2011-01-01

    There is substantial evidence that fluoride, through different applications and formulas, works to control caries development. The first observations of fluoride's effects on dental caries were linked to fluoride naturally present in the drinking water, and then from controlled water fluoridation programs. Other systemic methods to deliver fluoride were later suggested, including dietary fluoride supplements such as salt and milk. These systemic methods are now being questioned due to the fact that many studies have indicated that fluoride's action relies mainly on its post-eruptive effect from topical contact with the tooth structure. It is known that even the methods of delivering fluoride known as 'systemic' act mainly through a topical effect when they are in contact with the teeth. The effectiveness of water fluoridation in many geographic areas is lower than in previous eras due to the widespread use of other fluoride modalities. Nevertheless, this evidence should not be interpreted as an indication that systemic methods are no longer relevant ways to deliver fluoride on an individual basis or for collective health programs. Caution must be taken to avoid excess ingestion of fluoride when prescribing dietary fluoride supplements for children in order to minimize the risk of dental fluorosis, particularly if there are other relevant sources of fluoride intake - such as drinking water, salt or milk and/or dentifrice. Safe and effective doses of fluoride can be achieved when combining topical and systemic methods.

  7. Adsorption of fluoride onto crystalline titanium dioxide: effect of pH, ionic strength, and co-existing ions.

    PubMed

    Babaeivelni, Kamel; Khodadoust, Amid P

    2013-03-15

    Adsorption of fluoride from water onto titanium dioxide (TiO(2)) powder was investigated. The sorbent was crystalline TiO(2) composed of mostly anatase with a specific surface area of 56 m(2)/g. Adsorption kinetics and isotherm experiments were performed using an aqueous solution with bicarbonate alkalinity representative of natural waters. Adsorption kinetics data showed that maximum adsorption of fluoride occurred within 3h, following a pseudo-second order kinetics model. Adsorption isotherm data followed the Langmuir equation, indicating favorable adsorption of fluoride onto TiO(2), while results from the Dubinin-Radushkevich model are indicative of physical adsorption of fluoride. Adsorption of fluoride increased with decreasing solution pH. Maximum adsorption of fluoride occurred within the pH range of 2-5, while approximately 75% of maximum adsorption was obtained in the pH range of 7-8 with rapidly declining adsorption above pH 9. The pH(pzc) data for TiO(2) indicated the preferred adsorption of fluoride onto the acidic surface of TiO(2). Higher bicarbonate concentrations in solution increased the solution pH which was conducive to a decrease in adsorption of fluoride onto the surface of TiO(2) at higher pH. Overall, the solution pH was the main factor controlling the uptake of fluoride by TiO(2).

  8. Preparation and stability of ethanol-free solution of [18F]florbetapir ([18F]AV-45) for positron emission tomography amyloid imaging.

    PubMed

    Hayashi, Kazutaka; Tachibana, Akiko; Tazawa, Shusaku; Mizukawa, Yosuke; Osaki, Katsuhiko; Morimoto, Yoko; Zochi, Riyo; Kurahashi, Masahiro; Aki, Hatsumi; Takahashi, Kazuhiro

    2013-05-15

    We have developed an ethanol-free formulation method of [(18) F]florbetapir ([(1) (8) F]AV-45) using a commercially available automated JFE multi-purpose synthesizer. We have also evaluated the radiochemical stability in an ethanol-free solution of [(18) F]AV-45 under visible light irradiation and dark conditions by comparison with a conventional 10% ethanol solution of [(18) F]AV-45. [(18) F]AV-45 was obtained with a radiochemical yield of 55.1 ± 2.2% (decay-corrected to end of bombardment), specific activity of 591.6 ± 90.3 GBq/µmol and radiochemical purity of >99% within a total synthesis time of about 73 min. The radiochemical purity of [(18) F]AV-45 formulated by dissolving the ethanol-free solution was found to decrease as a function of the period of exposure to visible light. In contrast, the visible light photolysis could be suppressed by adding 10% ethanol to the formulation or by avoiding exposure to visible light. In the radiosynthesis of [(18) F]AV-45 formulated by dissolving the ethanol-free solution, [(18) F]AV-45 could be obtained with high radiochemical purity and high stability by avoiding exposure to visible light.

  9. Specific, reversible binding of [18F]benperidol to baboon D2 receptors: PET evaluation of an improved 18F-labeled ligand.

    PubMed

    Moerlein, S M; Perlmutter, J S; Welch, M J

    1995-08-01

    [18F]Benperidol ([18F]BP), a positron-emitting analogue of the dopaminergic D2 antagonist benperidol, was evaluated as a radiopharmaceutical for use with positron emission tomography (PET). PET imaging of baboons after i.v. injection of [18F]BP indicated that the radiofluorinated ligand rapidly localized in vivo within dopaminergic receptor-rich cerebral tissues, and that selective disposition was retained for over 2 h. Pretreatment of an animal with unlabeled receptor-specific antagonists prior to injection of [18F]BP confirmed that the radioligand bound specifically to central D2 receptors in vivo, and not to S2 or D1 receptors. [18F]BP bound to D2 receptors in a reversible manner; unlabeled eticlopride displaced D2 receptor-bound [18F]BP in vivo. The radioligand was metabolized in the periphery to polar metabolites which are not expected to cross the blood-brain barrier. [18F]BP has advantages over other tracers as a radiopharmaceutical for PET study of central D2 receptor activity, and can be applied for noninvasive evaluation of the interaction of unlabeled drugs with central D2 receptor sites.

  10. [18F]CFT [(18F)WIN 35,428], a radioligand to study the dopamine transporter with PET: characterization in human subjects.

    PubMed

    Laakso, A; Bergman, J; Haaparanta, M; Vilkman, H; Solin, O; Hietala, J

    1998-03-01

    We have characterized the usage of [18F]CFT (also known as [18F]WIN 35,428) as a radioligand for in vivo studies of human dopamine transporter by PET. CFT was labeled with 18F to a high specific activity, and dynamic PET scans were conducted in healthy volunteers at various time points up to 5 h from [18F]CFT injection. The regional distribution of [18F]CFT uptake correlated well with the known distribution of dopaminergic nerve terminals in the human brain and also with that of other dopamine transporter radioligands. Striatal binding peaked at 225 min after injection and declined thereafter, demonstrating the reversible nature of the binding to the dopamine transporter. Therefore, due to the relatively long half-life of 18F (109.8 min), PET scans with [18F]CFT could easily be conducted during the binding equilibrium, allowing estimation of Bmax/Kd values (i.e., binding potential). Binding potentials for putamen and caudate measured at equilibrium were 4.79+/-0.11 and 4.50+/-0.23, respectively. We were able to also visualize midbrain dopaminergic neurons (substantia nigra) with [18F]CFT in some subjects. In conclusion, the labeling of CFT with 18F allows PET scans to be conducted at binding equilibrium, and therefore a high signal-to-noise ratio and reliable quantification of binding potential can be achieved. With a high resolution 3D PET scanner, the quantification of extrastriatal dopamine transporters should become possible.

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

    PubMed Central

    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 [18F]FDG, have inadequate resolution for detection of small (2–3 mm) pancreatic tumors. We demonstrated the efficacy of PET imaging with an 18F-labeled lactose derivative, [18F]FEDL, that targets HIP/PAP, a biomarker that is overexpressed in the peritumoral pancreas. We developed another analogue, 1-[18F]fluoroethyl lactose ([18F]FEL), which is simpler to synthesize, 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. Tumor growth was monitored by bioluminescence imaging (BLI); accuracy of BLI tumor size estimates was verified by MRI in two representative mice. When the tumor size reached approximately 2–3 mm, the animals were injected with [18F]FEL (3.7 MBq) and underwent static PET/CT scans. Blood samples were collected at 2, 5, 10, 20 and 60 min after [18F]FEL injection to track blood clearance. Following imaging, animals were sacrificed and their organs and tumors/pancreatic tissue were collected and counted on a gamma counter. Pancreas, including tumor, was frozen, sliced and used for autoradiography and immunohistochemical analysis of HIP/PAP expression. Results Tumor growth was rapid, as observed by BLI and MRI. Blood clearance of [18F]FEL was bi-exponential, with half-lives of approximately 3.5 min and 40 min. Mean accumulation of [18F]FEL in the peritumoral 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. [18F]FEL was cleared predominantly by the kidneys. Comparative analysis of autoradiographic images and immunostaining results demonstrated a correlation between [18F]FEL binding and HIP/PAP expression. Conclusion

  12. Evaluation of [(18) F]BR420 and [(18) F]BR351 as radiotracers for MMP-9 imaging in colorectal cancer.

    PubMed

    Vazquez, Naiara; Missault, Stephan; Vangestel, Christel; Deleye, Steven; Thomae, David; Van der Veken, Pieter; Augustyns, Koen; Staelens, Steven; Dedeurwaerdere, Stefanie; Wyffels, Leonie

    2017-01-01

    MMP-9 is a zinc-dependent endopeptidase that is involved in the proteolytic degradation of the extracellular matrix and plays an important role in cancer migration, invasion, and metastasis. The aim of this study was to evaluate the potential of MMP-tracers [(18) F]BR420 and [(18) F]BR351 for MMP-9 imaging in a colorectal cancer xenograft model. [(18) F]BR420 and [(18) F]BR351 were synthesized using an automated synthesis module. For [(18) F]BR420, a novel and improved radiosynthesis was developed. Plasma stability and MMP-9-targeting capacity of both radiotracers was compared in the Colo205 colorectal cancer model. MMP-9 and MMP-2 expression levels in the tumors were evaluated by immunohistochemistry and in situ zymography. μPET imaging as well as ex vivo biodistribution revealed a higher tumor uptake for [(18) F]BR420 (3.15% ± 0.03% ID/g vs 0.94% ± 0.18% ID/g for [(18) F]BR351 at 2 hours pi) but slower blood clearance compared with [(18) F]BR351. [(18) F]BR351 was quickly metabolized in plasma with 20.28% ± 5.41% of intact tracer remaining at 15 minutes postinjection (PI). By contrast, [(18) F]BR420 displayed a higher metabolic stability with >86% intact tracer remaining at 2 hours PI. Immunohistochemistry revealed the presence of MMP-9 and MMP-2 in the tumor tissue, which was confirmed by in situ zymography. However, an autoradiography analysis of tracer distribution in the tumors did not correlate with MMP-9 expression. [(18) F]BR420 displayed a higher tumor uptake and higher stability compared with [(18) F]BR351 but a low tumor-to-blood ratio and discrepancy between tracer distribution and MMP-9 immunohistochemistry. Therefore, both tracers will not be usefulness for MMP-9 imaging in colorectal cancer.

  13. Multiphoton ionization/dissociation dynamics of formyl fluoride by velocity mapping ion imaging.

    PubMed

    Wang, Fengyan; Zhang, Yongwei; Wang, Hua; Liu, Jie; Jiang, Bo; Wang, Xiuyan; Yang, Xueming

    2009-10-21

    The dissociation dynamics of HFCO(+) ion has been studied using the velocity map ion imaging technique. The HFCO(+) ion is prepared by one-photon resonant three-photon ionization in the region of 43100-43860 cm(-1) excitation energy. The HFCO(+) ions, produced by multiphoton ionization, have sufficient internal energy to dissociate into the F and HCO(+) fragments without further absorption of another photon. Images of HCO(+) have been recorded at various excitation energies. It is noticed that the angular distributions of HCO(+) change dramatically from parallel distribution to perpendicular distribution and then back to parallel distribution in a very narrow excitation energy region of 43 473-43 500 cm(-1). Analysis of anisotropy parameters of beta(n) (n = 2, 4 and 6) reveals that the electronic states in the three-photon excitation of HFCO are mainly: HFCO(X(1)A') --> HFCO(A(1)A'') --> HFCO(A') --> HFCO(+)(A(2)A'';B(2)A'). The purely perpendicular resonant transitions are likely responsible for the perpendicular angular distribution of the HCO(+) ion fragment.

  14. Fluorides and non-fluoride remineralization systems.

    PubMed

    Amaechi, Bennett T; van Loveren, Cor

    2013-01-01

    Caries develops when the equilibrium between de- and remineralization is unbalanced favoring demineralization. De- and remineralization occur depending on the degree of saturation of the interstitial fluids with respect to the tooth mineral. This equilibrium is positively influenced when fluoride, calcium and phosphate ions are added favoring remineralization. In addition, when fluoride is present, it will be incorporated into the newly formed mineral which is then less soluble. Toothpastes may contain fluoride and calcium ions separately or together in various compounds (remineralization systems) and may therefore reduce demineralization and promote remineralization. Formulating all these compounds in one paste may be challenging due to possible premature calcium-fluoride interactions and the low solubility of CaF2. There is a large amount of clinical evidence supporting the potent caries preventive effect of fluoride toothpastes indisputably. The amount of clinical evidence of the effectiveness of the other remineralization systems is far less convincing. Evidence is lacking for head to head comparisons of the various remineralization systems.

  15. Synthesis and biological evaluation of positron emission tomography radiotracers targeting serotonin 4 receptors in brain: [18F]MNI-698 and [18F]MNI-699.

    PubMed

    Caillé, Fabien; Morley, Thomas J; Tavares, Adriana Alexandre S; Papin, Caroline; Twardy, Nicole M; Alagille, David; Lee, H Sharon; Baldwin, Ronald M; Seibyl, John P; Barret, Olivier; Tamagnan, Gilles D

    2013-12-01

    Two new benzodioxane derivatives were synthesized as candidates to image the serotonin 4 receptors by positron emission tomography (PET) and radiolabeled with fluorine-18 via a two-step procedure. Competition binding assays demonstrated that MNI-698 and MNI-699 had sub-nanomolar binding affinities against rat striatal 5-HT4 receptors (Ki of 0.20 and 0.07 nM, respectively). PET imaging in rhesus monkey showed that the regional brain distribution of [(18)F]MNI-698 and [(18)F]MNI-699 were consistent with the known densities of 5-HT4 in brain. [(18)F]MNI-698 and [(18)F]MNI-699 are among the first fluorine-18 radiotracers developed for imaging the 5-HT4 receptors in vivo and are currently under preclinical investigation in primates for future human use.

  16. Lymph Node Metastasis from Tall-Cell Thyroid Cancer Negative on 18F-FDG PET/CT and Detected by 18F-Choline PET/CT.

    PubMed

    Piccardo, Arnoldo; Massollo, Michela; Bandelloni, Roberto; Arlandini, Anselmo; Foppiani, Luca

    2015-08-01

    A 77-year-old woman underwent thyroidectomy and (131)I remnant ablation for tall-cell differentiated cancer (DTC) of the left lobe. Detectable Tg levels (4.1 μg/L) under TSH suppression, with undetectable serum Tg-antibody levels, prompted neck ultrasonography, which revealed a lymph node in the left laterocervical region and in the right retroclavicular region. (18)F-FDG PET/CT showed uptake by the left lymph node. (18)F-choline PET/CT showed increased uptake by both lymph nodes. Histopathology revealed DTC solid metastasis in the left lymph node and solid and cystic metastasis in the right one. (18)F-choline PET/CT can locate virulent DTC recurrence, thereby increasing (18)F-FDG PET/CT information.

  17. Evaluation of [18F]-(−)-Norchlorofluorohomoepibatidine ([18F]-(−)-NCFHEB) as a PET Radioligand to Image the Nicotinic Acetylcholine Receptors in Non-human Primates

    PubMed Central

    Bois, Frederic; Gallezot, Jean-Dominique; Zheng, Ming-Qiang; Lin, Shu-Fei; Esterlis, Irina; Cosgrove, Kelly P.; Carson, Richard E.; Huang, Yiyun

    2015-01-01

    Introduction The aims of the present study were to develop an optimized microfluidic method for the production of the selective nicotinic acetylcholine α4β2 receptor radiotracer [18F]-(−)-NCFHEB ([18F]-Flubatine) and to investigate its receptor binding profile and pharmacokinetic properties in rhesus monkeys in vivo. Methods [18F]-(−)-NCFHEB was prepared in two steps, a nucleophilic fluorination followed by N-Boc deprotection. PET measurements were performed in rhesus monkeys including baseline and preblocking experiments with nicotine (0.24 mg/kg). Radiometabolites in plasma were measured using HPLC. Results [18F]-(−)-NCFHEB was prepared in a total synthesis time of 140 min. The radiochemical purity in its final formulation was >98% and the mean specific radioactivity was 97.3 ± 16.1Bq/μmol (n = 6) at end of synthesis (EOS). In the monkey brain, radioactivity concentration was high in the thalamus, moderate in the putamen, hippocampus, frontal cortex, and lower in the cerebellum. Nicotine blocked 98–100% of [18F]-(−)-NCFHEB specific binding, and the non-displaceable distribution volume (VND) was estimated at 5.9 ± 1.0 mL/cm3 (n = 2), or 6.6 ± 1.1 mL/cm3 after normalization by the plasma free fraction fP. Imaging data are amenable to kinetic modeling analysis using the multilinear analysis (MA1) method, and model-derived binding parameters display good test-retest reproducibility. In rhesus monkeys, [18F]-(−)-NCFHEB can yield robust regional binding potential (BPND) values (thalamus = 4.1 ± 1.5, frontal cortex = 1.2 ± 0.2, putamen = 0.96 ± 0.45, cerebellum = 0.10 ± 0.29). Conclusion An efficient microfluidic synthetic method was developed for preparation of [18F]-(−)-NCFHEB. PET examination in rhesus monkeys showed that [18F]-(−)-NCFHEB entered the brain readily and its regional radioactivity uptake pattern was in accordance with the known distribution of α4β2 receptors. Estimated non-displaceable binding potential (BPND) values in brain

  18. [(18)F]FDG PET monitoring of tumour response to chemotherapy: does [(18)F]FDG uptake correlate with the viable tumour cell fraction?

    PubMed

    Spaepen, Karoline; Stroobants, Sigrid; Dupont, Patrick; Bormans, Guy; Balzarini, Jan; Verhoef, Gregor; Mortelmans, Luc; Vandenberghe, Peter; De Wolf-Peeters, Christine

    2003-05-01

    Because metabolic changes induced by chemotherapy precede the morphological changes, fluorine-18 fluorodeoxyglucose positron emission tomography ([(18)F]FDG PET) is thought to predict response to therapy earlier and more accurately than other modalities. To be a reliable predictor of response, changes in tumour [(18)F]FDG uptake should reflect changes in viable cell fraction, but little is known about the contribution of apoptotic and necrotic cancer cells and inflammatory tissue to the [(18)F]FDG signal. In a tumour mouse model we investigated the relation between chemotherapy-induced changes in various tumoral components and tumour uptake and size. SCID mice were subcutaneously inoculated in the right thigh with 5 x 10(6) Daudi cells. When the tumour measured 15-20 mm, Endoxan was given intravenously. At different time points [1-15 days (d1-d15) after the injection of Endoxan], ex vivo autoradiography and histopathology were performed in two mice and [(18)F]FDG uptake in the tumour and tumour size were correlated with the different cell fractions measured with flow cytometry in five mice. At d1/d3, similar reductions in [(18)F]FDG uptake and viable tumoral cell fraction were observed and these reductions preceded changes in tumour size. By d8/d10, [(18)F]FDG uptake had stabilised despite a further reduction in viable tumoral cell fraction. At these time points a major inflammatory response was observed. At d15, an increase in viable tumour cells was again observed and this was accurately predicted by an increase in [(18)F]FDG uptake, while the tumour volume remained unchanged. In contrast with variations in tumour volume, [(18)F]FDG is a good marker for chemotherapy response monitoring. However, optimal timing seems crucial since a transient increase in stromal reaction may result in overestimation of the fraction of viable cells.

  19. 18F-FLT and 18F-FDG PET/CT in Predicting Response to Chemoradiotherapy in Nasopharyngeal Carcinoma: Preliminary Results

    PubMed Central

    Qi, Shi; Zhongyi, Yang; Yingjian, Zhang; Chaosu, Hu

    2017-01-01

    The purpose of this study was to explore the feasibility of 18F-Fluorothymidine (18F-FLT) and 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in predicting treatment response of nasopharyngeal carcinoma (NPC). Patients with NPC of Stage II-IVB were prospectively enrolled, receiving 2 cycles of neoadjuvant chemotherapy (NACT), followed by concurrent chemoradiotherapy. Each patient underwent pretreatment and post-NACT FLT PET/CT and FDG PET/CT. Standard uptake values (SUV) and tumor volume were measured. Tumor response to NACT was evaluated before radiotherapy by MRI (magnetic resonance imaging), and tumor regression at the end of radiotherapy was evaluated at 55 Gy, according to RECIST 1.1 Criteria. Finally, 20 patients were consecutively enrolled. At the end of radiotherapy, 7 patients reached complete regression while others were partial regression. After 2 cycles of NACT both FLT and FDG parameters declined remarkably. Parameters of FDG PET were more strongly correlated to tumor regression than those of FLT PET.70% SUVmax was the best threshold to define contouring margin around the target. Some residual lesions after NACT showed by MRI were negative in PET/CT. Preliminary results showed both 18F-FDG and 18F-FLT PET have the potential to monitor and predict tumor regression. PMID:28091565

  20. High yield synthesis of 6-(/sup 18/F)fluoro-L-dopa by regioselective fluorination of protected L-dopa with (/sup 18/F)acetylhypofluorite

    SciTech Connect

    Chaly, T.; Diksic, M.

    1986-12-01

    Regioselective fluorination of a completely protected phosgene derivative of 3,4-dihydroxy-phenyl-L-alanine (5-(benzyl-3',4'-carbonate)-oxazolidine-2,5-dione) with gaseous /sup 18/F-labeled acetylhypofluorite and (/sup 18/F)F2 in acetonitrile is described. Fluorination with (/sup 18/F)acetylhypofluorite yields 6-(/sup 18/F)fluoro-L-dopa with 95% radiochemical purity; fluorination of the same substrate with (/sup 18/F)F2 yields a mixture of all three structural isomers in a ratio of 70:16:14 for 6-, 5-, and 2-fluoro compounds. Radiochemical yield, relative to (/sup 18/F) acetylhypofluorite, measured at the end of the synthesis, is (21 +/- 4)% (N = 8). The synthesis requires approximately 40 min (50 min if HPLC was done) and yields the final radiopharmaceutical in a two-step procedure. The specific activity of the final product was approximately 763 mCi/mmol at the end of a 40-min synthesis when 30-min irradiation was used.

  1. Functional imaging of the brain with/sup 18/F-fluorodeoxyglucose

    SciTech Connect

    Reivich, M; Greenberg, J; Alavi, A; Hand, P; Rintelmann, W; Rosenquist, A; Christman, D; Fowler, J; MacGregor, R; Wolf, A

    1980-01-01

    A techniques is reported by which it is possible to determine which regions of the human brain become functionally active in response to a specific stimulus. The method utilizes /sup 18/F-2-fluoro-2-deoxyglucose ((/sup 18/F)-FDG) administered as a bolus. (/sup 18/F)-FDG is used as a tracer for the exchange of glucose between plasma and brain and its phosphorylation. The subject is then scanned during administration of a physiologic stimulus by position emission tomography and the three-dimensional distribution of /sup 18/F activity in the brain determined. (ACR)

  2. Copper-Mediated Radiofluorination of Arylstannanes with [18F]KF

    PubMed Central

    2016-01-01

    A copper-mediated nucleophilic radiofluorination of aryl- and vinylstannanes with [18F]KF is described. This method is fast, uses commercially available reagents, and is compatible with both electron-rich and electron-deficient arene substrates. This method has been applied to the manual synthesis of a variety of clinically relevant radiotracers including protected [18F]F-phenylalanine and [18F]F-DOPA. In addition, an automated synthesis of [18F]MPPF is demonstrated that delivers a clinically validated dose of 200 ± 20 mCi with a high specific activity of 2400 ± 900 Ci/mmol. PMID:27718581

  3. Normal variations and benign findings in pediatric 18F-FDG-PET/CT.

    PubMed

    Grant, Frederick D

    2014-04-01

    (18)F-FDG PET and PET/CT have a wide variety of indications in children and young adults. Oncologic indications are the most common, but others include neurology, sports medicine, cardiology, and infection imaging. Accurate interpretation of pediatric (18)F-FDG PET and PET/CT requires a technically adequate study and knowledgeable interpretation of the images. A successful pediatric (18)F-FDG PET requires age-appropriate patient preparation and consideration of patient age and developmental stage. Accurate interpretation of the study requires familiarity with normal patterns of physiologic (18)F-FDG uptake in children at all stages of development.

  4. Gas-phase reactions of microsolvated fluoride ions: an investigation of different solvents.

    PubMed

    Eyet, Nicole; Villano, Stephanie M; Bierbaum, Veronica M

    2013-02-14

    The gas-phase reactions of F(-)(DMSO), F(-)(CH(3)CN), and F(-)(C(6)H(6)) with t-butyl halides were investigated. Reaction rate constants, kinetic isotope effects, and product ion branching ratios were measured using the flowing afterglow selected ion flow tube technique (FA-SIFT). Additionally, the structure of F(-)(DMSO) was investigated both computationally and experimentally, and two stable isomers were identified. The reactions generally proceed by elimination mechanisms; however, the reaction of F(-)(C(6)H(6)) with t-butyl chloride occurs by a switching mechanism. These reactions are compared to previous studies of microsolvated reactions of t-butyl halides where the solvent molecules were polar, protic molecules.

  5. Structural Investigation of Fluoridated POSS Cages Using Ion Mobility Mass Spectrometry and Molecular Mechanics (Preprint)

    DTIC Science & Technology

    2008-01-09

    organic polymer. For example, the low surface energy properties of fluorinated POSS compounds have been used to augment both fluorinated and non... fluorinated polymers.10-13 Many POSS monomers have been successfully characterized using MALDI techniques14-16 in conjunction with ion mobility mass...nucleophilic attack, are shown in blue. Negative contours, showing susceptibility to electrophilic attack, are shown in red. The positive contour of

  6. Human radiation dosimetry of 6-[{sup 18}F]FDG predicted from preclinical studies

    SciTech Connect

    Muzic, Raymond F.; Chandramouli, Visvanathan; Hatami, Ahmad; Huang, Hsuan-Ming; Wu, Chunying; Ismail-Beigi, Faramarz

    2014-03-15

    Purpose: The authors are developing 6-[{sup 18}F]fluoro-6-deoxy-D-glucose (6-[{sup 18}F]FDG) as an in vivo tracer of glucose transport. While 6-[{sup 18}F]FDG has the same radionuclide half-life as 2-[{sup 18}F]fluoro-2-deoxy-D-glucose (2-[{sup 18}F]FDG) which is ubiquitously used for PET imaging, 6-[{sup 18}F]FDG has special biologic properties and different biodistributions that make it preferable to 2-[{sup 18}F]FDG for assessing glucose transport. In preparation for 6-[{sup 18}F]FDG use in human PET scanning, the authors would like to determine the amount of 6-[{sup 18}F]FDG to inject while maintaining radiation doses in a safe range. Methods: Rats were injected with 6-[{sup 18}F]FDG, euthanized at specified times, and tissues were collected and assayed for activity content. For each tissue sample, the percent of injected dose per gram was calculated and extrapolated to that for humans in order to construct predicted time-courses. Residence times were calculated as areas under the curves and were used as inputs to OLINDA/EXM in order to calculate the radiation doses. Results: Unlike with 2-[{sup 18}F]FDG for which the urinary bladder wall receives the highest absorbed dose due to urinary excretion, with 6-[{sup 18}F]FDG there is little urinary excretion and osteogenic cells and the liver are predicted to receive the highest absorbed doses: 0.027 mGy/MBq (0.100 rad/mCi) and 0.018 mGy/MBq (0.066 rad/mCi), respectively. Also, the effective dose from 6-[{sup 18}F]FDG, i.e., 0.013 mSv/MBq (0.046 rem/mCi), is predicted to be approximately 30% lower than that from 2-[{sup 18}F]FDG. Conclusions: 6-[{sup 18}F]FDG will be safe for use in the PET scanning of humans.

  7. Freestanding manganese dioxide nanosheet network grown on nickel/polyvinylidene fluoride coaxial fiber membrane as anode materials for high performance lithium ion batteries

    NASA Astrophysics Data System (ADS)

    Zhang, Yan; Luo, Zhongping; Xiao, Qizhen; Sun, Tianlei; Lei, Gangtie; Li, Zhaohui; Li, Xiaojing

    2015-11-01

    A novel manganese dioxide (MnO2) nanosheet network grown on nickel/polyvinylidene fluoride (Ni/PVDF) coaxial fiber membrane is successfully fabricated by a three-step route: the polyvinylidene fluoride fiber membrane is prepared by electrospinning method, and then the Ni(shell)/PVDF(core) coaxial fiber membrane with core-shell structure can be obtained by the electroless deposition, and finally the manganese dioxide nanosheet network grown on Ni/PVDF coaxial fiber membrane can be achieved by using a simple hydrothermal treatment. This as-prepared binder-free and flexible composite membrane is directly used as anode for lithium ion batteries. The excellent electrochemical performance of the composite membrane can be attributed to the unique combinative effects of nanosized MnO2 network and conductive Ni/PVDF fiber matrix as well as the porous structure of composite fiber membrane.

  8. Synthesis and Preclinical Characterization of [18F]FPBZA: A Novel PET Probe for Melanoma

    PubMed Central

    Huang, Shih-Pin; Lo, Yen-Chen; Liu, Ren-Shyan; Shen, Chih-Chieh

    2014-01-01

    Introduction. Benzamide can specifically bind to melanoma cells. A 18F-labeled benzamide derivative, [18F]N-(2-diethylaminoethyl)-4-[2-(2-(2-fluoroethoxy) ethoxy)ethoxy]benzamide ([18F]FPBZA), was developed as a promising PET probe for primary and metastatic melanoma. Methods. [18F]FPBZA was synthesized via a one-step radiofluorination in this study. The specific uptake of [18F]FPBZA was studied in B16F0 melanoma cells, A375 amelanotic melanoma cells, and NB-DNJ-pretreated B16F0 melanoma cells. The biological characterization of [18F]FPBZA was performed on mice bearing B16F0 melanoma, A375 amelanotic melanoma, or inflammation lesion. Results. [18F]FPBZA can be prepared efficiently with a yield of 40–50%. The uptake of [18F]FPBZA by B16F0 melanoma cells was significantly higher than those by A375 tumor cells and NB-DNJ-pretreated B16F0 melanoma cells. B16F0 melanoma displayed prominent uptake of [18F]FPBZA at 2 h (7.81 ± 0.82 %ID/g), compared with A375 tumor and inflammation lesion (3.00 ± 0.71 and 1.67 ± 0.56 %ID/g, resp.). [18F]FPBZA microPET scan clearly delineated B16F0 melanoma but not A375 tumor and inflammation lesion. In mice bearing pulmonary metastases, the lung radioactivity reached 4.77 ± 0.36 %ID/g at 2 h (versus 1.16 ± 0.23 %ID/g in normal mice). Conclusions. Our results suggested that [18F]FPBZA PET would provide a promising and specific approach for the detection of primary and metastatic melanoma lesions. PMID:25254219

  9. Inclusive Neutron Production by 790 Mev/nucleon Neon Ions on Lead and Sodium Fluoride

    NASA Astrophysics Data System (ADS)

    Baldwin, Alan Richard

    The inclusive double-differential cross sections for neutron production were measured at angles of 0, 15, 30, 50, 70, 90, 120, and 160 degrees. The neutrons were produced by 790 MeV/nucleon Neon ions bombarding targets of Pb and NaF. A striking peak in the zero degree spectra at a neutron energy slightly below the beam energy per nucleon is suggested to be particle evaporation superimposed on the broader fragmentation process predicted by statistical models. The Lorentz-invariant cross section at 0 degrees in the rest frame of the projectile are interpreted to include three processes of neutron emission: (1) the excitation and evaporative decay of the projectile spectator provides an estimate for the temperature of 3.5 +/- 0.7 and 3.4 +/- 0.7 MeV/k for Ne-Pb and Ne-NaF collisions, (2) the fragmentation of a neutron from the projectile yielded a Fermi momentum of 295 +/- 22 and 259 +/- 22 MeV/c for the Neon ion in the Ne-Pb and Ne-NaF collisions respectively, and (3) the high-energy tail may be explained by backscattering of a neutron in the target from a cluster of nucleons in the projectile with an average cluster size of about 1.2 nucleons.

  10. Ferret thoracic anatomy by 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (18F-FDG PET/CT) imaging.

    PubMed

    Wu, Albert; Zheng, Huaiyu; Kraenzle, Jennifer; Biller, Ashley; Vanover, Carol D; Proctor, Mary; Sherwood, Leslie; Steffen, Marlene; Ng, Chin; Mollura, Daniel J; Jonsson, Colleen B

    2012-01-01

    The domestic ferret (Mustela putorius furo) has been a long-standing animal model used in the evaluation and treatment of human diseases. Molecular imaging techniques such as 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) positron emission tomography (PET) would be an invaluable method of tracking disease in vivo, but this technique has not been reported in the literature. Thus, the aim of this study was to establish baseline imaging characteristics of PET/computed tomography (CT) with (18)F-FDG in the ferret model. Twelve healthy female ferrets were anesthetized and underwent combined PET/CT scanning. After the images were fused, volumes of interest (VOIs) were generated in the liver, heart, thymus, and bilateral lung fields. For each VOI, standardized uptake values (SUVs) were calculated. Additional comparisons were made between radiotracer uptake periods (60, 90, and >90 minutes), intravenous and intraperitoneal injections of (18)F-FDG, and respiratory gated and ungated acquisitions. Pulmonary structures and the surrounding thoracic and upper abdominal anatomy were readily identified on the CT scans of all ferrets and were successfully fused with PET. VOIs were created in various tissues with the following SUV calculations: heart (maximum standardized uptake value [SUV(Max)] 8.60, mean standardized uptake value [SUV(Mean)] 5.42), thymus (SUV(Max) 3.86, SUV(Mean) 2.59), liver (SUV(Max) 1.37, SUV(Mean) 0.99), right lung (SUV(Max) 0.92, SUV(Mean) 0.56), and left lung (SUV(Max) 0.88, SUV(Mean) 0.51). Sixty- to 90-minute uptake periods were sufficient to separate tissues based on background SUV activity. No gross differences in image quality were seen between intraperitoneal and intravenous injections of (18)F-FDG. Respiratory gating also did not have a significant impact on image quality of lung parenchyma. The authors concluded that (18)F-FDG PET and CT imaging can be performed successfully in normal healthy ferrets with the parameters identified in this study. They

  11. Ferret Thoracic Anatomy by 2-Deoxy-2-(18F)Fluoro-D-Glucose (18F-FDG) Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) Imaging

    PubMed Central

    Wu, Albert; Zheng, Huaiyu; Kraenzle, Jennifer; Biller, Ashley; Vanover, Carol D.; Proctor, Mary; Sherwood, Leslie; Steffen, Marlene; Ng, Chin; Mollura, Daniel J.; Jonsson, Colleen B.

    2013-01-01

    The domestic ferret (Mustela putorius furo) has been a long-standing animal model used in the evaluation and treatment of human diseases. Molecular imaging techniques such as 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography (PET) would be an invaluable method of tracking disease in vivo, but this technique has not been reported in the literature. Thus, the aim of this study was to establish baseline imaging characteristics of PET/computed tomography (CT) with 18F-FDG in the ferret model. Twelve healthy female ferrets were anesthetized and underwent combined PET/CT scanning. After the images were fused, volumes of interest (VOIs) were generated in the liver, heart, thymus, and bilateral lung fields. For each VOI, standardized uptake values (SUVs) were calculated. Additional comparisons were made between radiotracer uptake periods (60, 90, and >90 minutes), intravenous and intraperitoneal injections of 18F-FDG, and respiratory gated and ungated acquisitions. Pulmonary structures and the surrounding thoracic and upper abdominal anatomy were readily identified on the CT scans of all ferrets and were successfully fused with PET. VOIs were created in various tissues with the following SUV calculations: heart (maximum standardized uptake value [SUVMax] 8.60, mean standardized uptake value [SUVMean] 5.42), thymus (SUVMax 3.86, SUVMean 2.59), liver (SUVMax 1.37, SUVMean 0.99), right lung (SUVMax 0.92, SUVMean 0.56), and left lung (SUVMax 0.88, SUVMean 0.51). Sixty- to 90-minute uptake periods were sufficient to separate tissues based on background SUV activity. No gross differences in image quality were seen between intraperitoneal and intravenous injections of 18F-FDG. Respiratory gating also did not have a significant impact on image quality of lung parenchyma. The authors concluded that 18F-FDG PET and CT imaging can be performed successfully in normal healthy ferrets with the parameters identified in this study. They obtained similar imaging

  12. Novel indole based dual responsive 'turn-on' chemosensor for fluoride ion detection

    NASA Astrophysics Data System (ADS)

    Jeyanthi, Dharmaraj; Iniya, Murugan; Krishnaveni, Karuppiah; Chellappa, Duraisamy

    2015-02-01

    An efficient new dual channel chemosensor 2,3-bis((E)-(1H-indole-3-yl)methyleneamino)maleonitrile (DN) which exhibits selective sensing of F- ions in DMSO, was synthesized by a facile one step condensation reaction of indole-3-carboxaldehyde with diaminomaleonitrile. The probe DN was characterized by elemental analysis, 1H, 13C-NMR, ESI-MS and IR spectral techniques. Upon addition of F-, DN induces remarkable changes in both absorption and fluorescence spectra on the basis of charge transfer mechanism. The receptor DN serves for highly selective, sensitive detection of F- without the interference of other relevant anions. The Job's plot analysis indicates the binding stoichiometry to be 1:1 (host/guest).

  13. Norharmane: old yet highly selective dual channel ratiometric fluoride and hydrogen sulfate ion sensor.

    PubMed

    Mallick, Arabinda; Katayama, Tetsuro; Ishibasi, Yukihide; Yasuda, Masakazu; Miyasaka, Hiroshi

    2011-01-21

    Norharmane provides a simple unexplored class of anion receptor, that allows for the ratiometric selective detection of F(-) and HSO(4)(-) ions. The presence of a strong base can easily form hydrogen bonds with the acidic hydrogen bond donor moiety and the relatively strong acid can easily protonate the basic hydrogen bond acceptor moiety, which can modulate the optical response and can detect the anions efficiently with high selectivity. In view of that, it is promising to conceive the use of these systems in various sensing applications as well as in other situations, such as anion transport and purification, where the availability of cheap and easy-to-make anion receptors, would be advantageous.

  14. Process for the production of 18F-2-deoxy-2-fluoro-D-glucose

    DOEpatents

    Shiue, Chyng-Yann; Salvadori, Piero A.; Wolf, Alfred P.; Fowler, Joanna S.; MacGregor, Robert R.

    1986-05-06

    Process for the production of 2-deoxy-2-fluoro-D-glucose and the corresponding .sup.18 F-compound by the reaction of acetyl hypofluorite or the corresponding .sup.18 F-compound with 3,4,6-tri-O-acetyl-D-glucal followed by hydrolysis. Process includes the production of the hypofluorite compound at ambient temperature.

  15. Process for the production of 18F-2-deoxy-2-fluoro-D-glucose

    DOEpatents

    Shiue, Chyng-Yann; Salvadori, Piero A.; Wolf, Alfred P.; Fowler, Joanna S.; MacGregor, Robert R.

    1986-01-01

    Process for the production of 2-deoxy-2-fluoro-D-glucose and the corresponding .sup.18 F-compound by the reaction of acetyl hypofluorite or the corresponding .sup.18 F-compound with 3,4,6-tri-O-acetyl-D-glucal followed by hydrolysis. Process includes the production of the hypofluorite compound at ambient temperature.

  16. Process for the production of /sup 18/F-2-deoxy-2-fluoro-d-glucose

    DOEpatents

    Shiue, C.Y.; Salvadori, P.A.; Wolf, A.P.; Fowler, J.S.; MacGregor, R.R.

    Process is given for the production of 2-deoxy-2-fluoro-D-glucose and the corresponding /sup 18/F-compound by the reaction of acetyl hypofluorite or the corresponding /sup 18/F-compound with 3,4,6-tri-0-acetyl-D-glucal followed by hydrolysis. Process includes the production of the hypofluorite compound at ambient temperature.

  17. Candida Esophagitis Incidentally Detected by 18F-FDG PET/CT in Metastatic Lung Adenocarcinoma

    PubMed Central

    Martínez-Amador, N; Martínez-Rodríguez, I; Quirce, R; Jiménez-Bonilla, J; Banzo, I

    2017-01-01

    The diagnostic significance of esophageal 18F-FDG uptake in oncologic patient is challenging. It may represent normal physiological uptake, inflammation, infection, or neoplasia. We present a patient with a recent diagnosis of non-small cell lung cancer stage IV and esophageal mild uptake on 18F-FDG PET/CT scan. Biopsy of esophageal mucosa demonstrated Candida esophagitis.

  18. Limits of [18F]-FLT PET as a Biomarker of Proliferation in Oncology

    PubMed Central

    McKinley, Eliot T.; Ayers, Gregory D.; Smith, R. Adam; Saleh, Samir A.; Zhao, Ping; Washington, Mary Kay; Coffey, Robert J.; Manning, H. Charles

    2013-01-01

    Background Non-invasive imaging biomarkers of cellular proliferation hold great promise for quantifying response to personalized medicine in oncology. An emerging approach to assess tumor proliferation utilizes the positron emission tomography (PET) tracer 3’-deoxy-3’[18F]-fluorothymidine, [18F]-FLT. Though several studies have associated serial changes in [18F]-FLT-PET with elements of therapeutic response, the degree to which [18F]-FLT-PET quantitatively reflects proliferative index has been continuously debated for more that a decade. The goal of this study was to elucidate quantitative relationships between [18F]-FLT-PET and cellular metrics of proliferation in treatment naïve human cell line xenografts commonly employed in cancer research. Methods and Findings [18F]-FLT-PET was conducted in human cancer xenograft-bearing mice. Quantitative relationships between PET, thymidine kinase 1 (TK1) protein levels and immunostaining for proliferation markers (Ki67, TK1, PCNA) were evaluated using imaging-matched tumor specimens. Overall, we determined that [18F]-FLT-PET reflects TK1 protein levels, yet the cell cycle specificity of TK1 expression and the extent to which tumors utilize thymidine salvage for DNA synthesis decouple [18F]-FLT-PET data from standard estimates of proliferative index. Conclusions Our findings illustrate that [18F]-FLT-PET reflects tumor proliferation as a function of thymidine salvage pathway utilization. Unlike more general proliferation markers, such as Ki67, [18F]-FLT PET reflects proliferative indices to variable and potentially unreliable extents. [18F]-FLT-PET cannot discriminate moderately proliferative, thymidine salvage-driven tumors from those of high proliferative index that rely primarily upon de novo thymidine synthesis. Accordingly, the magnitude of [18F]-FLT uptake should not be considered a surrogate of proliferative index. These data rationalize the diversity of [18F]-FLT-PET correlative results previously reported and

  19. Construction and Evaluation of Quantitative Small-Animal PET Probabilistic Atlases for [18F]FDG and [18F]FECT Functional Mapping of the Mouse Brain

    PubMed Central

    Casteels, Cindy; Vunckx, Kathleen; Aelvoet, Sarah-Ann; Baekelandt, Veerle; Bormans, Guy; Van Laere, Koen; Koole, Michel

    2013-01-01

    Automated voxel-based or pre-defined volume-of-interest (VOI) analysis of small-animal PET data in mice is necessary for optimal information usage as the number of available resolution elements is limited. We have mapped metabolic ([18F]FDG) and dopamine transporter ([18F]FECT) small-animal PET data onto a 3D Magnetic Resonance Microscopy (MRM) mouse brain template and aligned them in space to the Paxinos co-ordinate system. In this way, ligand-specific templates for sensitive analysis and accurate anatomical localization were created. Next, using a pre-defined VOI approach, test-retest and intersubject variability of various quantification methods were evaluated. Also, the feasibility of mouse brain statistical parametric mapping (SPM) was explored for [18F]FDG and [18F]FECT imaging of 6-hydroxydopamine-lesioned (6-OHDA) mice. Methods Twenty-three adult C57BL6 mice were scanned with [18F]FDG and [18F]FECT. Registrations and affine spatial normalizations were performed using SPM8. [18F]FDG data were quantified using (1) an image-derived-input function obtained from the liver (cMRglc), using (2) standardized uptake values (SUVglc) corrected for blood glucose levels and by (3) normalizing counts to the whole-brain uptake. Parametric [18F]FECT binding images were constructed by reference to the cerebellum. Registration accuracy was determined using random simulated misalignments and vectorial mismatch determination. Results Registration accuracy was between 0.21–1.11 mm. Regional intersubject variabilities of cMRglc ranged from 15.4% to 19.2%, while test-retest values were between 5.0% and 13.0%. For [18F]FECT uptake in the caudate-putamen, these values were 13.0% and 10.3%, respectively. Regional values of cMRglc positively correlated to SUVglc measured within the 45–60 min time frame (spearman r = 0.71). Next, SPM analysis of 6-OHDA-lesioned mice showed hypometabolism in the bilateral caudate-putamen and cerebellum, and an unilateral striatal decrease in DAT

  20. Synthesis and biological characterisation of 18F-SIG343 and 18F-SIG353, novel and high selectivity σ2 radiotracers, for tumour imaging properties

    PubMed Central

    2013-01-01

    Background Sigma2 (σ2) receptors are highly expressed in cancer cell lines and in tumours. Two novel selective 18F-phthalimido σ2 ligands, 18F-SIG343 and 18F-SIG353, were prepared and characterised for their potential tumour imaging properties. Methods Preparation of 18F-SIG343 and 18F-SIG353 was achieved via nucleophilic substitution of their respective nitro precursors. In vitro studies including radioreceptor binding assays in the rat brain membrane and cell uptake studies in the A375 cell line were performed. In vivo studies were carried out in mice bearing A375 tumours including positron emission tomography (PET) imaging, biodistribution, blocking and metabolite studies. Results In vitro studies showed that SIG343 and SIG353 displayed excellent affinity and selectivity for σ2 receptors (Ki(σ2) = 8 and 3 nM, σ2:σ1 = 200- and 110-fold, respectively). The σ2 selectivity of 18F-SIG343 was further confirmed by blocking studies in A375 cells, however, not noted for 18F-SIG353. Biodistribution studies showed that both radiotracers had similar characteristics including moderately high tumour uptake (4%ID/g to 5%ID/g); low bone uptake (3%ID/g to 4%ID/g); and high tumour-to-muscle uptake ratios (four- to sevenfold) up to 120 min. Although radiotracer uptake in organs known to express σ receptors was significantly blocked by pre-injection of competing σ ligands, the blocking effect was not observed in the tumour. PET imaging studies indicated major radioactive localisation in the chest cavity for both ligands, with approximately 1%ID/g uptake in the tumour at 120 min. Metabolite studies showed that the original radiotracers remained unchanged 65% to 80% in the tumour up to 120 min. Conclusions The lead ligands showed promising in vitro and in vivo characteristics. However, PET imaging indicated low tumour-to-background ratios. Furthermore, we were unable to demonstrate that uptake in the A375 tumour was σ2-specific. 18F-SIG343 and 18F-SIG343 do not

  1. Mapping of fluoride endemic areas and assessment of fluoride exposure.

    PubMed

    Viswanathan, Gopalan; Jaswanth, A; Gopalakrishnan, S; Siva ilango, S

    2009-02-15

    The prevalence of fluorosis is mainly due to the consumption of more fluoride through drinking water. It is necessary to find out the fluoride endemic areas to adopt remedial measures to the people on the risk of fluorosis. The objectives of this study are to estimate the fluoride exposure through drinking water from people of different age group and to elucidate the fluoride endemic areas through mapping. Assessment of fluoride exposure was achieved through the estimation fluoride level in drinking water using fluoride ion selective electrode method. Google earth and isopleth technique were used for mapping of fluoride endemic areas. From the study it was observed that Nilakottai block of Dindigul district in Tamil Nadu is highly fluoride endemic. About 88% of the villages in this block have fluoride level more than the prescribed permissible limit in drinking water. Exposure of fluoride among different age groups was calculated in this block, which comprises 32 villages. The maximum estimated exposure doses were 0.19 mg/kg/day for infants, 0.17 mg/kg/day for children and 0.10 mg/kg/day for adults. When compared with adequate intake of minimal safe level exposure dose of 0.01 mg/kg/day for infants and 0.05 mg/kg/day for other age groups, a health risk due to fluorosis to the people in Nilakottai block has become evident. From the results, the people in Nilakottai block are advised to consume drinking water with fluoride level less than 1 mg/l. It has been recommended to the government authorities to take serious steps to supply drinking water with low fluoride concern for the fluorosis affected villages.

  2. Vacuum ultraviolet photon-mediated production of [(18) F]F2.

    PubMed

    Krzyczmonik, Anna; Keller, Thomas; Kirjavainen, Anna K; Forsback, Sarita; Solin, Olof

    2017-04-01

    The chemistry of F2 and its derivatives are amenable to facile aliphatic or aromatic substitution, as well as electrophilic addition. The main limitation in the use of [(18) F]F2 for radiopharmaceutical synthesis is the low specific activity achieved by the traditional methods of production. The highest specific activities, 55 GBq/μmol, for [(18) F]F2 have been achieved so far by using electrical discharge in the post-target production of [(18) F]F2 gas from [(18) F]CH3 F. We demonstrate that [(18) F]F2 is produced by illuminating a gas mixture of neon/F2 /[(18) F]CH3 F with vacuum ultraviolet photons generated by an excimer laser. We tested several illumination chambers and production conditions. The effects of the initial amount of [(18) F]F(-) , amount of carrier F2 , and number of 193-nm laser pulses at constant power were evaluated regarding radiochemical yield and specific activity. The specific activity attained for [(18) F]F2 -derived [(18) F]NFSi was 10.3 ± 0.9 GBq/μmol, and the average radiochemical yield over a wide range of conditions was 6.7% from [(18) F]F(-) . The production can be improved by optimization of the synthesis device and procedures. The use of a commercially available excimer laser and the simplicity of the process can make this method relatively easy for adaptation in radiochemistry laboratories.

  3. 150 μA 18F- target and beam port upgrade for the IBA 18/9 cyclotron

    NASA Astrophysics Data System (ADS)

    Stokely, M. H.; Peeples, J. L.; Poorman, M. C.; Magerl, M.; Siemer, T.; Brisard, P.; Wieland, B. W.

    2012-12-01

    A high power (˜3 kW) target platform has been developed for the IBA 18/9 cyclotron. New designs for the airlock, collimator and target subsystems have been fabricated and deployed. The primary project goal is reliable commercial production of 18F- at 150 μA or greater, while secondary goals include improving serviceability and extending service intervals relative to OEM systems. Reliable operation in a production environment has been observed at beam currents up to 140 μA. Challenges include ion source lifetime and localized peaking in the beam intensity distribution.

  4. 150 {mu}A 18F{sup -} target and beam port upgrade for the IBA 18/9 cyclotron

    SciTech Connect

    Stokely, M. H.; Peeples, J. L.; Poorman, M. C.; Magerl, M.; Siemer, T.; Brisard, P.; Wieland, B. W.

    2012-12-19

    A high power ({approx}3 kW) target platform has been developed for the IBA 18/9 cyclotron. New designs for the airlock, collimator and target subsystems have been fabricated and deployed. The primary project goal is reliable commercial production of 18F{sup -} at 150 {mu}A or greater, while secondary goals include improving serviceability and extending service intervals relative to OEM systems. Reliable operation in a production environment has been observed at beam currents up to 140 {mu}A. Challenges include ion source lifetime and localized peaking in the beam intensity distribution.

  5. Polyvinylidene fluoride membrane by novel electrospinning system for separator of Li-ion batteries

    NASA Astrophysics Data System (ADS)

    Yang, Cuiru; Jia, Zhidong; Guan, Zhicheng; Wang, Liming

    The remarkable characteristics of nanofibers mats electrospun are large surface area to volume ratio and high porosity, which are crucial to increase the ionic conductivity of membrane full of liquid electrolyte, in this aspect, electrospinning is prior to the other methods, such as dry method, wet method, etc. Therefore, fabricating the separator of Li-ion batteries by electrospinning is potential and promising. The PVDF membranes were fabricated by electrospinning. The experiment demonstrated that the main deficiency in the fabricating separators process by electrospinning was low mechanical property, which induced partial short circuits inside the cells. Several methods were presented to enhance the mechanical strength. The experiments demonstrated that the higher the solution concentration was, the stronger the mechanical strength was, and the higher the voltage was, the stronger the mechanical strength was. Additionally, the spherical hat collection target instead of conditional plane target was applied in the electrospinning system, as a result, the thickness of the membrane was more uniform and the fiber diameter was also more uniform. Therefore, the charge and discharge capacity of the coin type cell composed of the separator collected by spherical hat target exceeded the plane target, and the electrospinning separators exceeded the commercial polypropylene separator.

  6. Vigorous Appraisal of Fluoride on Industrial Proponent in Thermal Power Plant over Anthropoid Biosphere Using F− Ion-Selective Electrode

    PubMed Central

    Pandey, Prem Chandra; Yadav, Manoj; Katiyar, Swati; Mandal, Vinay Prasad; Singh, Ram Kumar; Tomar, Vandana; Rani, Meenu

    2015-01-01

    This study was conducted to analyze the impact of fluoride in the anthropogenic condition in an industrial region promoting and affecting the health of the workers. Fluoride is toxic to humans in high concentrations, such as can occur in persons working in fluoride-containing mineral industries like aluminum industries. When workers are exposed to fluoride-containing minerals, they can suffer from a variety of health problems, such as dental disease. This paper presents the relationship of different clinical conditions correlated against the fluoride level. Contributing clinical aspects, such as morbidity, dysentery, overcrowding, and skin disease, are also studied to assess the consequences of fluoride upon consistent exposure. The relationship between pH and hardness of water with fluoride was measured, and then spatial maps were generated. The investigations resulted in a conclusion that hardness of water had a more pronounced impact on the level of fluoride concentration as compared with pH. Water with more hardness contains more fluoride concentration (25 mg/ml) as compared with soft water (4 mg/ml). This paper also revealed the concentration of fluoride content in the bodies of aluminum plant workers, which varied from 0.06 to 0.17 mg/L of blood serum in the case of pot room workers and 0.01 to 0.04 mg/L in the case of non-pot room workers. In fingernails, it varied from 0.09 to 3.77 mg/L and 0.39 to 1.15 mg/L in the case of pot room and non-pot room workers, respectively. In urine, it varied from 0.53 to 9.50 mg/L in pot room workers and 0.29 to 1.80 mg/L in non-pot room workers. This paper concluded that water was safe for drinking purposes if it has a low hardness (60–140 mg/ml) and pH (7.1–7.4). PMID:27170909

  7. Vigorous Appraisal of Fluoride on Industrial Proponent in Thermal Power Plant over Anthropoid Biosphere Using F(-) Ion-Selective Electrode.

    PubMed

    Pandey, Prem Chandra; Kumar, Pavan; Yadav, Manoj; Katiyar, Swati; Mandal, Vinay Prasad; Singh, Ram Kumar; Tomar, Vandana; Rani, Meenu

    2015-01-01

    This study was conducted to analyze the impact of fluoride in the anthropogenic condition in an industrial region promoting and affecting the health of the workers. Fluoride is toxic to humans in high concentrations, such as can occur in persons working in fluoride-containing mineral industries like aluminum industries. When workers are exposed to fluoride-containing minerals, they can suffer from a variety of health problems, such as dental disease. This paper presents the relationship of different clinical conditions correlated against the fluoride level. Contributing clinical aspects, such as morbidity, dysentery, overcrowding, and skin disease, are also studied to assess the consequences of fluoride upon consistent exposure. The relationship between pH and hardness of water with fluoride was measured, and then spatial maps were generated. The investigations resulted in a conclusion that hardness of water had a more pronounced impact on the level of fluoride concentration as compared with pH. Water with more hardness contains more fluoride concentration (25 mg/ml) as compared with soft water (4 mg/ml). This paper also revealed the concentration of fluoride content in the bodies of aluminum plant workers, which varied from 0.06 to 0.17 mg/L of blood serum in the case of pot room workers and 0.01 to 0.04 mg/L in the case of non-pot room workers. In fingernails, it varied from 0.09 to 3.77 mg/L and 0.39 to 1.15 mg/L in the case of pot room and non-pot room workers, respectively. In urine, it varied from 0.53 to 9.50 mg/L in pot room workers and 0.29 to 1.80 mg/L in non-pot room workers. This paper concluded that water was safe for drinking purposes if it has a low hardness (60-140 mg/ml) and pH (7.1-7.4).

  8. Physiologic conditions affect toxicity of ingested industrial fluoride.

    PubMed

    Sauerheber, Richard

    2013-01-01

    The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity from ingestion is distinct from fully soluble toxic industrial fluorides. The toxicity of fluoride is determined by environmental conditions and the positive cations present. At a pH typical of gastric juice, fluoride is largely protonated as hydrofluoric acid HF. Industrial fluoride ingested from treated water enters saliva at levels too low to affect dental caries. Blood levels during lifelong consumption can harm heart, bone, brain, and even developing teeth enamel. The widespread policy known as water fluoridation is discussed in light of these findings.

  9. Physiologic Conditions Affect Toxicity of Ingested Industrial Fluoride

    PubMed Central

    Sauerheber, Richard

    2013-01-01

    The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity from ingestion is distinct from fully soluble toxic industrial fluorides. The toxicity of fluoride is determined by environmental conditions and the positive cations present. At a pH typical of gastric juice, fluoride is largely protonated as hydrofluoric acid HF. Industrial fluoride ingested from treated water enters saliva at levels too low to affect dental caries. Blood levels during lifelong consumption can harm heart, bone, brain, and even developing teeth enamel. The widespread policy known as water fluoridation is discussed in light of these findings. PMID:23840230

  10. Instability of Polyvinylidene Fluoride-Based Polymeric Binder in Lithium-Ion Cells: Final Report

    SciTech Connect

    Garcia, M.; Nagasubramanian, G.; Tallant, D.R.; Roth, E.P.

    1999-05-01

    Thermal instabilities were identified in SONY-type lithium-ion cells and correlated with interactions of cell constituents and reaction products. Three temperature regions of interaction were identified and associated with the state of charge (degree of Li intercalation) of the cell. Anodes were shown to undergo exothermic reactions as low as 100 degree C involving the solid electrolyte interface (SEI) layer and the LiPF(6) salt in the electrolyte (EC-PC:DEC/IM LiPF(6)). These reactions could account for the thermal runaway observed in these cells beginning at 100 degree C. Exothermic reactions were also observed in the 200 degree C to 300 degree C region between the intercalated lithium anodes, the LiPF(6) salt, and the PVDF. These reactions were followed by a high-temperature reaction region, 300 degree C to 400 degree C, also involving the PVDF binder and the intercalated lithium anodes. The solvent was not directly involved in these reactions but served as a moderator and transport medium. Cathode exothermic reactions with the PVDF binder were observed above 200 degree C and increased with the state of charge (decreasing Li content). The stability of the PVDF binder as a function of electrochemical cycling was studied using FTIR. The infrared spectra from the extracts of both electrodes indicate that PVDF is chemically modified by exposure to the lithium cell electrolyte (as well as electrochemical cycling) in conjunction with NMP extraction. Preconditioning of PVDF to dehydrohalogenation, which may be occurring by reaction with LiPf(6), makes the PVDF susceptible to attack by a range of nucleophiles.

  11. Synthesis of 2'-deoxy-2'-[.sup.18F]fluoro-5-methyl-1-B-D-arabinofuranosyluracil (.sup.18F-FMAU)

    DOEpatents

    Li, Zibo; Cai, Hancheng; Conti, Peter S

    2014-12-16

    The present invention relates to methods of synthesizing .sup.18F-FMAU. In particular, .sup.18F-FMAU is synthesized using one-pot reaction conditions in the presence of Friedel-Crafts catalysts. The one-pot reaction conditions are incorporated into a fully automated cGMP-compliant radiosynthesis module, which results in a reduction in synthesis time and simplifies reaction conditions. The one-pot reaction conditions are also suitable for the production of 5-substituted thymidine or cytidine analogs. The products from the one-pot reaction (e.g. the labeled thymidine or cytidine analogs) can be used as probes for imaging tumor proliferative activity. More specifically, these [.sup.18F]-labeled thymidine or cytidine analogs can be used as a PET tracer for certain medical conditions, including, but not limited to, cancer disease, autoimmunity inflammation, and bone marrow transplant.

  12. Radiosynthesis and pharmacokinetics of [18F]fluoroethyl bufalin in hepatocellular carcinoma-bearing mice

    PubMed Central

    Yang, Zhaoshuo; Liu, Jianhua; Huang, Qingqing; Zhang, Zhouji; Zhang, Jiawei; Pan, Yanjia; Yang, Yunke; Cheng, Dengfeng

    2017-01-01

    Purpose Bufalin, the main component of a Chinese traditional medicine chansu, shows convincing anticancer effects in a lot of tumor cell lines. However, its in vivo behavior is still unclear. This research aimed to evaluate how bufalin was dynamically absorbed after intravenous injection in animal models. We developed a radiosynthesis method of [18F]fluoroethyl bufalin to noninvasively evaluate the tissue biodistribution and pharmacokinetics in hepatocellular carcinoma-bearing mice. Methods [18F]fluoroethyl bufalin was synthesized with conjugation of 18F-CH2CH2OTs and bufalin. The radiochemical purity was proved by the radio-high-performance liquid chromatography (HPLC). The pharmacokinetic studies of [18F]fluoroethyl bufalin were then performed in Institute of Cancer Research (ICR) mice. Furthermore, the biodistribution and metabolism of [18F]fluoroethyl bufalin in HepG2 and SMMC-7721 tumor-bearing nude mice were studied in vivo by micro-positron emission tomography (micro-PET). Results The radiochemical purity (RCP) of [18F]fluoroethyl bufalin confirmed by radio-HPLC was 99%±0.18%, and [18F]fluoroethyl bufalin showed good in vitro and in vivo stabilities. Blood dynamics of [18F]fluoroethyl bufalin conformed to the two compartments in the ICR mice model. The pharmacokinetic parameters of [18F]fluoroethyl bufalin were calculated by DAS 2.0 software. The area under concentration–time curve (AUC0–t) and the values of clearance (CL) were 540.137 μg/L·min and 0.001 L/min/kg, respectively. The half-life of distribution (t1/2α) and half-life of elimination (t1/2β) were 0.693 and 510.223 min, respectively. Micro-PET imaging showed that [18F]fluoroethyl bufalin was quickly distributed via the blood circulation; the major tissue biodistribution of [18F]fluoroethyl bufalin in HepG2 and SMMC-7721 tumor-bearing mice was liver and bladder. Conclusion [18F]fluoroethyl bufalin was accumulated rapidly in the liver at an early time point (5 min) post injection (pi) and

  13. [18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity

    PubMed Central

    Kim, Woosuk; Le, Thuc M.; Wei, Liu; Poddar, Soumya; Bazzy, Jimmy; Wang, Xuemeng; Uong, Nhu T.; Abt, Evan R.; Capri, Joseph R.; Austin, Wayne R.; Van Valkenburgh, Juno S.; Steele, Dalton; Gipson, Raymond M.; Slavik, Roger; Cabebe, Anthony E.; Taechariyakul, Thotsophon; Yaghoubi, Shahriar S.; Lee, Jason T.; Sadeghi, Saman; Lavie, Arnon; Faull, Kym F.; Witte, Owen N.; Donahue, Timothy R.; Phelps, Michael E.; Herschman, Harvey R.; Herrmann, Ken; Czernin, Johannes; Radu, Caius G.

    2016-01-01

    Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside (dN) salvage pathway, is an important therapeutic and positron emission tomography (PET) imaging target in cancer. PET probes for dCK have been developed and are effective in mice but have suboptimal specificity and sensitivity in humans. To identify a more suitable probe for clinical dCK PET imaging, we compared the selectivity of two candidate compounds—[18F]Clofarabine; 2-chloro-2′-deoxy-2′-[18F]fluoro-9-β-d-arabinofuranosyl-adenine ([18F]CFA) and 2′-deoxy-2′-[18F]fluoro-9-β-d-arabinofuranosyl-guanine ([18F]F-AraG)—for dCK and deoxyguanosine kinase (dGK), a dCK-related mitochondrial enzyme. We demonstrate that, in the tracer concentration range used for PET imaging, [18F]CFA is primarily a substrate for dCK, with minimal cross-reactivity. In contrast, [18F]F-AraG is a better substrate for dGK than for dCK. [18F]CFA accumulation in leukemia cells correlated with dCK expression and was abrogated by treatment with a dCK inhibitor. Although [18F]CFA uptake was reduced by deoxycytidine (dC) competition, this inhibition required high dC concentrations present in murine, but not human, plasma. Expression of cytidine deaminase, a dC-catabolizing enzyme, in leukemia cells both in cell culture and in mice reduced the competition between dC and [18F]CFA, leading to increased dCK-dependent probe accumulation. First-in-human, to our knowledge, [18F]CFA PET/CT studies showed probe accumulation in tissues with high dCK expression: e.g., hematopoietic bone marrow and secondary lymphoid organs. The selectivity of [18F]CFA for dCK and its favorable biodistribution in humans justify further studies to validate [18F]CFA PET as a new cancer biomarker for treatment stratification and monitoring. PMID:27035974

  14. [18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity.

    PubMed

    Kim, Woosuk; Le, Thuc M; Wei, Liu; Poddar, Soumya; Bazzy, Jimmy; Wang, Xuemeng; Uong, Nhu T; Abt, Evan R; Capri, Joseph R; Austin, Wayne R; Van Valkenburgh, Juno S; Steele, Dalton; Gipson, Raymond M; Slavik, Roger; Cabebe, Anthony E; Taechariyakul, Thotsophon; Yaghoubi, Shahriar S; Lee, Jason T; Sadeghi, Saman; Lavie, Arnon; Faull, Kym F; Witte, Owen N; Donahue, Timothy R; Phelps, Michael E; Herschman, Harvey R; Herrmann, Ken; Czernin, Johannes; Radu, Caius G

    2016-04-12

    Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside (dN) salvage pathway, is an important therapeutic and positron emission tomography (PET) imaging target in cancer. PET probes for dCK have been developed and are effective in mice but have suboptimal specificity and sensitivity in humans. To identify a more suitable probe for clinical dCK PET imaging, we compared the selectivity of two candidate compounds-[(18)F]Clofarabine; 2-chloro-2'-deoxy-2'-[(18)F]fluoro-9-β-d-arabinofuranosyl-adenine ([(18)F]CFA) and 2'-deoxy-2'-[(18)F]fluoro-9-β-d-arabinofuranosyl-guanine ([(18)F]F-AraG)-for dCK and deoxyguanosine kinase (dGK), a dCK-related mitochondrial enzyme. We demonstrate that, in the tracer concentration range used for PET imaging, [(18)F]CFA is primarily a substrate for dCK, with minimal cross-reactivity. In contrast, [(18)F]F-AraG is a better substrate for dGK than for dCK. [(18)F]CFA accumulation in leukemia cells correlated with dCK expression and was abrogated by treatment with a dCK inhibitor. Although [(18)F]CFA uptake was reduced by deoxycytidine (dC) competition, this inhibition required high dC concentrations present in murine, but not human, plasma. Expression of cytidine deaminase, a dC-catabolizing enzyme, in leukemia cells both in cell culture and in mice reduced the competition between dC and [(18)F]CFA, leading to increased dCK-dependent probe accumulation. First-in-human, to our knowledge, [(18)F]CFA PET/CT studies showed probe accumulation in tissues with high dCK expression: e.g., hematopoietic bone marrow and secondary lymphoid organs. The selectivity of [(18)F]CFA for dCK and its favorable biodistribution in humans justify further studies to validate [(18)F]CFA PET as a new cancer biomarker for treatment stratification and monitoring.

  15. Effect of fluoride on calcium ion concentration and expression of nuclear transcription factor kappa-B ρ65 in rat hippocampus.

    PubMed

    Zhang, Jing; Zhu, Wen-Jing; Xu, Xiao-Hong; Zhang, Zi-Gui

    2011-07-01

    The study investigated the neurotoxicity of drinking water fluorosis in rat hippocampus. Just weaning male Sprague-Dawley (SD) rats were given 15, 30, 60 mg/L NaF solution and tap water for 9 months. The calcium ion concentration ([Ca(2+)]) in synaptosomes was measured by double wavelength fluorescence spectrophotometer and the expression level of nuclear transcription factor kappa-B ρ65 (NF-κB ρ65) in hippocampal CA3 region was measured by immunohistochemistry. The results showed that [Ca(2+)] significantly increased (F = 33.218, P < 0.01) in moderate fluoride group compared with the control group, and the expression level of NF-κB ρ65 in CA3 region presented an increasing trend as fluoride concentration increased. These results indicate that increase of synaptosomes [Ca(2+)] and NF-κB ρ65 expression level may be the molecular basis of central nervous system damage caused by chronic fluoride intoxication. NF-κB ρ65 in CA3 region is probably a target molecule for fluorosis.

  16. Evaluation of 6-([18F] fluoroacetamido)-1-hexanoic-anilide (18F-FAHA) as imaging probe in tumor xenograft mice model

    NASA Astrophysics Data System (ADS)

    Li, Fiona; Cho, Sung Ju; Yu, Lihai; Hudson, Robert H. E.; Luyt, Leonard G.; Pin, Christopher L.; Kovacs, Michael S.; Koropatnick, James; Lee, Ting-Yim

    2016-03-01

    Alteration in genetic expression is as important as gene mutation in cancer development and proliferation. Epigenetic changes affect gene expression without altering the DNA sequence. Histone deacetylase (HDAC), an enzyme facilitating histone remodelling, can lead to silencing of tumor suppressor genes making HDAC inhibitors viable anticancer drugs against tumors with increased activity of the enzyme. In this study we evaluated 18F-fluroacetamido-1-hexanoicanilide (18F-FAHA), an artificial HDAC substrate, as imaging probe of HDAC activity of human tumor xenografts in immunocompromised host mice. Human breast and melanoma cell lines, MDA-MB-468 and MDA-MB-435 respectively, known to overexpress HDAC activity were xenografted into immunocompromised mice and HDAC activity was imaged using 18F-FAHA. The melanoma group was treated with saline, SAHA (suberoylanilide hydroxamic acid, an approved anticancer HDAC inhibitor) in DMSO, or DMSO as positive control. Tracer kinetic modelling and SUV were used to estimate HDAC activity from dynamic PET data. Both breast tumor and melanoma group showed great variability in binding rate constant (BRC) of 18F-FAHA suggesting highly variable inter- and intra-tumoral HDAC activity. For the SAHA treated melanoma group, HDAC activity, as monitored by BRC of 18F-FAHA, decreased more than the two (positive and negative) control groups but not tumor growth. Our preliminary study showed that noninvasive PET imaging with 18F-FAHA has the potential to identify patients for whom treatment with HDAC inhibitors are appropriate, to assess the effectiveness of that treatment as an early marker of target reduction, and also eliminate the need for invasive tissue biopsy to individualize treatment.

  17. Quantitation of fluoride ion released sarin in red blood cell samples by gas chromatography-chemical ionization mass spectrometry using isotope dilution and large-volume injection.

    PubMed

    Jakubowski, E M; McGuire, J M; Evans, R A; Edwards, J L; Hulet, S W; Benton, B J; Forster, J S; Burnett, D C; Muse, W T; Matson, K; Crouse, C L; Mioduszewski, R J; Thomson, S A

    2004-01-01

    A new method for measuring fluoride ion released isopropyl methylphosphonofluoridate (sarin, GB) in the red blood cell fraction was developed that utilizes an autoinjector, a large-volume injector port (LVI), positive ion ammonia chemical ionization detection in the SIM mode, and a deuterated stable isotope internal standard. This method was applied to red blood cell (RBC) and plasma ethyl acetate extracts from spiked human and animal whole blood samples and from whole blood of minipigs, guinea pigs, and rats exposed by whole-body sarin inhalation. Evidence of nerve agent exposure was detected in plasma and red blood cells at low levels of exposure. The linear method range of quantitation was 10-1000 pg on-column with a detection limit of approximately 2-pg on-column. In the course of method development, several conditions were optimized for the LVI, including type of injector insert, injection volume, initial temperature, pressure, and flow rate. RBC fractions had advantages over the plasma with respect to assessing nerve agent exposure using the fluoride ion method especially in samples with low serum butyrylcholinesterase activity.

  18. Analysis of induced radionuclides in replacement parts and liquid wastes in a medical cyclotron solely used for production of 18F for [18F]FDG.

    PubMed

    Mochizuki, S; Ishigure, N; Ogata, Y; Kobayashi, T

    2013-04-01

    Radioactivities produced in replacement parts and liquid wastes in a medical cyclotron used to produce (18)F for [(18)F]FDG with 10MeV protons were analyzed. Nineteen radionuclides were found in the replacement parts and liquid wastes. Among them, long-lived (56)Co in the Havar foils is critical in terms of radioactive waste management. The estimated dose level of exposure for the operating staff during the replacement of parts was around 310μSv/y, which is smaller than the recommended dose limit for workers.

  19. Transition-state structure for the quintessential SN2 reaction of a carbohydrate: reaction of α-glucopyranosyl fluoride with azide ion in water.

    PubMed

    Chan, Jefferson; Sannikova, Natalia; Tang, Ariel; Bennet, Andrew J

    2014-09-03

    We report that the SN2 reaction of α-d-glucopyranosyl fluoride with azide ion proceeds through a loose (exploded) transition-state (TS) structure. We reached this conclusion by modeling the TS using a suite of five experimental kinetic isotope effects (KIEs) as constraints for the calculations. We also report that the anomeric (13)C-KIE is not abnormally large (k12/k13 = 1.024 ± 0.006), a finding which is at variance with the previous literature value (Zhang et al. J. Am. Chem. Soc. 1994, 116, 7557).

  20. Selective 2-( sup 18 F)fluorodopa uptake for melanogenesis in murine metastatic melanomas

    SciTech Connect

    Ishiwata, K.; Kubota, K.; Kubota, R.; Iwata, R.; Takahashi, T.; Ido, T. )

    1991-01-01

    The relationship between 3,4-dihydroxy-2-({sup 18}F)fluoro-L-phenylalanine (2-({sup 18}F)FDOPA) uptake and melanogenesis was studied using mice bearing two B16 melanomas: B16-F1 has a higher melanin synthesis ability and a slower growing rate than the higher metastatic B16-F10. A significantly higher 2-({sup 18}F)FDOPA uptake by B16-F1 than by B16-F10 and a reverse relationship for the uptake of ({sup 14}C) 2-deoxy-2-fluoro-D-glucose and ({sup 3}H)thymidine were observed 1 hr postinjection. F1-to-F10 ratios of both the 2-({sup 18}F)FDOPA uptake and the acid-insoluble radioactivity increased to about 5 at 6 hr, which paralleled the melanin content. FM3A mammary carcinoma showed a 2-({sup 18}F)FDOPA uptake similar to the B16-F10 but without the acid-insoluble radioactivity. With D,L-DOPA loading, a 55% decreased uptake by FM3A 1 hr postinjection was significantly greater than the 20% reduction in both melanomas. O-Methylated 2-({sup 18}F)FDOPA was a predominant acid-soluble metabolite in all tumors. Whole-body autoradiography discriminated the two melanomas clearly. 2-({sup 18}F)FDOPA may be a promising tracer for the selective imaging of melanogenesis.

  1. Sweetening Pharmaceutical Radiochemistry by 18F-Fluoroglycosylation: A Short Review

    PubMed Central

    Maschauer, Simone

    2014-01-01

    At the time when the highly efficient [18F]FDG synthesis was discovered by the use of the effective precursor 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-β-D-mannopyranose (mannose triflate) for nucleophilic 18F-substitution, the field of PET in nuclear medicine experienced a long-term boom. Thirty years later, various strategies for chemoselective 18F-labeling of biomolecules have been developed, trying to keep up with the emerging field of radiopharmaceutical sciences. Among the new radiochemical strategies, chemoselective 18F-fluoroglycosylation methods aim at the sweetening of pharmaceutical radiochemistry by providing a powerful and highly valuable tool for the design of 18F-glycoconjugates with suitable in vivo properties for PET imaging studies. This paper provides a short review (reflecting the literature not older than 8 years) on the different 18F-fluoroglycosylation reactions that have been applied to the development of various 18F-glycoconjugate tracers, including not only peptides, but also nonpeptidic tracers and high-molecular-weight proteins. PMID:24991541

  2. 18F-fluorodeoxyglucose positron-emission tomography-computed tomography to diagnose recurrent cancer

    PubMed Central

    You, J J; Cline, K J; Gu, C-S; Pritchard, K I; Dayes, I S; Gulenchyn, K Y; Inculet, R I; Dhesy-Thind, S K; Freeman, M A; Chan, A M; Julian, J A; Levine, M N

    2015-01-01

    Background: Sometimes the diagnosis of recurrent cancer in patients with a previous malignancy can be challenging. This prospective cohort study assessed the clinical utility of 18F-fluorodeoxyglucose positron-emission tomography-computed tomography (18F-FDG PET-CT) in the diagnosis of clinically suspected recurrence of cancer. Methods: Patients were eligible if cancer recurrence (non-small-cell lung (NSCL), breast, head and neck, ovarian, oesophageal, Hodgkin's or non-Hodgkin's lymphoma) was suspected clinically, and if conventional imaging was non-diagnostic. Clinicians were asked to indicate their management plan before and after 18F-FDG PET-CT scanning. The primary outcome was change in planned management after 18F-FDG PET-CT. Results: Between April 2009 and June 2011, 101 patients (age, median 65 years; 55% female) were enroled from four cancer centres in Ontario, Canada. Distribution by primary tumour type was: NSCL (55%), breast (19%), ovarian (10%), oesophageal (6%), lymphoma (6%), and head and neck (4%). Of the 99 subjects who underwent 18F-FDG PET-CT, planned management changed after 18F-FDG PET-CT in 52 subjects (53%, 95% confidence interval (CI), 42–63%); a major change in plan from no treatment to treatment was observed in 38 subjects (38%, 95% CI, 29–49%), and was typically associated with 18F-FDG PET-CT findings that were positive for recurrent cancer (37 subjects). After 3 months, the stated post-18F-FDG PET-CT management plan was actually completed in 88 subjects (89%, 95% CI, 81–94%). Conclusion: In patients with suspected cancer recurrence and conventional imaging that is non-diagnostic, 18F-FDG PET-CT often provides new information that leads to important changes in patient management. PMID:25942398

  3. Simple and efficient synthesis of 2-[(18)F]fluoroethyl triflate for high yield (18)fluoroethylation.

    PubMed

    Peters, Tanja; Vogg, Andreas; Oppel, Iris M; Schmaljohann, Jörn

    2014-12-01

    The [(18)F]fluoroethyl moiety has been widely utilized in the synthesis of (18)F-labelled compounds. The aim of this work was the reliable synthesis of [(18)F]FEtOTf with a novel strategy to increase the reactivity of the commonly used [(18)F]FEB and [(18)F]FEtOTos. [(18)F]FEtOTf and the intermediate [(18)F]FEtOH were synthesized in high RCY (78% and 85%, respectively) and purified by SPE. The high potency of [(18)F]FEtOTf was shown by the efficient alkylation of the deactivated nucleophile aniline under mild conditions, as well as by the synthesis of [(18)F]FEC.

  4. Bottled Water and Fluoride

    MedlinePlus

    ... Fluoridation Journal Articles for Community Water Fluoridation Bottled Water Recommend on Facebook Tweet Share Compartir Consumers drink ... questions about bottled water and fluoride. Does bottled water contain fluoride? Bottled water products may contain fluoride, ...

  5. A case of gouty arthritis to tophi on 18F-FDG PET/CT imaging.

    PubMed

    Ito, Kimiteru; Minamimoto, Ryogo; Morooka, Miyako; Kubota, Kazuo

    2012-06-01

    We report a case of gouty arthritis with tophi that was evaluated using 18F-fluorodeoxyglucose (FDG) positron emission tomography. A 77-year-old man with a history of gouty attacks was admitted with severe polyarticular pain and fever. 18F-FDG positron emission tomography/CT demonstrated focal uptake at multiple joints, including the juxta-articular soft-tissue-density masses of the elbows, and the bases of bilateral large toes. Gouty arthritis should be considered with focal 18F-FDG uptake in juxta-articular soft-tissue-density masses (tophi) with or without associated erosions.

  6. Synthesis and evaluation of 18F labeled alanine derivatives as potential tumor imaging agents

    PubMed Central

    Wang, Limin; Zha, Zhihao; Qu, Wenchao; Qiao, Hongwen; Lieberman, Brian P.; Plössl, Karl; Kung, Hank F.

    2012-01-01

    Introduction This paper reports the synthesis and labeling of 18F alanine derivatives. We also investigate their biological characteristics as potential tumor imaging agents mediated by alanine-serine-cysteine preferring (ASC) transporter system. Methods Three new 18F alanine derivatives were prepared from corresponding tosylate-precursors through a two-step labelling reaction. In vitro uptake studies to evaluate and to compare these three analogs were carried out in 9L glioma and PC-3 prostate cancer cell lines. Potential transport mechanisms, protein incorporation and stability of 3-(1-[18F]fluoromethyl)-L-alanine (L[18F]FMA) were investigated in 9L glioma cells. Its biodistribution was determined in a rat-bearing 9L tumor model. PET imaging studies were performed on rat bearing 9L glioma tumors and transgenic mouse carrying spontaneous generated M/tomND tumor (mammary gland adenocarcinoma). Results New 18F alanine derivatives were prepared with 7–34% uncorrected radiochemical yields, excellent enantiomeric purity (>99%) and good radiochemical purity (>99%). In vitro uptake of the L-[18F]FMA in 9L glioma and PC-3 prostate cancer cells was higher than those observed for other two alanine derivatives and [18F]FDG in first 1 h. Inhibition of cell uptake studies suggested that L-[18F]FMA uptake in 9L glioma was predominantly via transport system ASC. After entering into cells, L-[18F]FMA remained stable and was not incorporated into protein within 2 h. In vivo biodistribution studies demonstrated that L-[18F]FMA had relatively high uptake in liver and kidney. Tumor uptake was fast, reaching a maximum within 30 min. The tumor-to-muscle, tumor-to-blood and tumor-to-brain ratios at 60 min post injection were 2.2, 1.9 and 3.0, respectively. In PET imaging studies, tumors were visualized with L-[18F]FMA in both 9L rat and transgenic mouse. Conclusion L-[18F]FMA showed promising properties as a PET imaging agent for up-regulated ASC transporter associated with tumor

  7. Florbetapir (18F) for brain amyloid positron emission tomography: highlights on the European marketing approval.

    PubMed

    Cortes-Blanco, Anabel; Prieto-Yerro, Concha; Martinez-Lazaro, Raul; Zamora, Javier; Jiménez-Huete, Adolfo; Haberkamp, Marion; Pohly, Johannes; Enzmann, Harald; Zinserling, Jörg; Strassmann, Valerie; Broich, Karl

    2014-10-01

    Florbetapir (18F) for brain amyloid positron emission tomography (PET) imaging has been recently approved in Europe to estimate β-amyloid neuritic plaque density in the brain when the subject is still alive. Such density is one of the key issues for the definitive diagnosis of Alzheimer's disease (AD) at autopsy. This capability of florbetapir (18F) is regarded as a significant improvement in the diagnostic procedures for adult patients with cognitive impairment who are being evaluated for AD and other causes of cognitive impairment. The current paper highlights the specific characteristics of the European marketing authorization of florbetapir (18F).

  8. DFT/TDDFT investigation of the modulation of photochromic properties in an organoboron-based diarylethene by fluoride ions.

    PubMed

    Liu, Shujuan; Sun, Shi; Wang, Chuanming; Zhao, Qiang; Sun, Huibin; Li, Fuyou; Fan, Quli; Huang, Wei

    2011-02-07

    The diarylethene derivative 1,2-bis-(5'-dimesitylboryl-2'-methylthieny-3'-yl)-cyclopentene (1) containing dimesitylboryl groups is an interesting photochromic material. The dimesitylboryl groups can bind to F(-), which tunes the optical and electronic properties of the diarylethene compound. Hence, the diarylethene derivative 1 containing dimesitylboryl groups is sensitive to both light and F(-), and its photochromic properties can be tuned by a fluoride ion. Herein, we studied the substituent effect of dimesitylboron groups on the optical properties of both the closed-ring and open-ring isomers of the diarylethene molecule by DFT/TDDFT calculations and found that these methods are reliable for the determination of the lowest singlet excitation energies of diarylethene compounds. The introduction of dimesitylboron groups to the diarylethene compound can elongate its conjugation length and change the excited-state properties from π→π* transition to a charge-transfer state. This explains the modulation of photochromic properties through the introduction of dimesitylboron groups. Furthermore, the photochromic properties can be tuned through the binding of F(-) to a boron center and the excited state of the diarylethene compound is changed from a charge-transfer state to a π→π* transition. Hence, a subtle control of the photochromic spectroscopic properties was realized. In addition, the changes of electronic characteristics by the isomerization reaction of diarylethene compounds were also investigated with theoretical calculations. For the model compound 2 without dimesitylboryl groups, the closed-ring isomer has better hole- and electron-injection abilities, as well as higher charge-transport rates, than the open-ring isomer. The introduction of dimesitylboron groups to diarylethene can dramatically improve the charge-injection and -transport abilities. The closed isomer of compound 1 (1 C) has the best hole- and electron-injection abilities, whereas the

  9. Quantitative differences in [(18)F] NaF PET/CT: TOF versus non-TOF measurements.

    PubMed

    Oldan, Jorge D; Turkington, Timothy G; Choudhury, Kingshuk; Chin, Bennett B

    2015-01-01

    [(18)F] sodium fluoride (NaF) PET/CT is a current, clinically relevant method to assess bone metastases. Time-of-flight (TOF) PET provides better statistical data quality, which can improve either lower image noise or improve resolution, or both, depending on the image reconstruction. Improved resolution can improve quantitative measurements of standardized uptake value (SUV) in small structures. These quantitative differences may be important in both clinical interpretation and multicenter clinical trials where quantification is integral to assessing response to therapy. The purpose of this study is to determine if and by how much SUV quantitatively differs between TOF and conventional non-TOF reconstructions in [(18)F] NaF PET/CT. SUV measurements (mean and maximum) were compared in TOF and non-TOF [(18)F] NaF PET-CT reconstructions for 47 prostate cancer patients in normal regions including: soft tissue (n=282 total regions; liver, aorta, posterior abdominal fat, bladder, brain, and paraspinal muscles), and osseous structures (n=188; T12 vertebral body, femoral diaphyseal cortex, femoral head, and lateral rib). Comparisons were also made for benign degenerative changes (n=281) and metastases (n=159). TOF and non-TOF SUVs were assessed with paired t-test and linear correlations. Normal soft tissue showed lower SUVmean for TOF compared to non-TOF in liver, brain, and adipose. All osseous structures showed higher SUVmean for TOF compared to non-TOF including normal regions, degenerative joint disease, and metastases. For all metastatic lesions, the average SUVmean increased by 2.5%, and in degenerative joint disease it increased by 3.5% on TOF reconstructions. Smaller lesion size was a significant factor influencing this increase in SUVmean. TOF SUVmean values are higher in osseous structures and lower in background soft tissue structures. While these differences are statistically significant, the magnitudes of these changes are relatively modest. Smaller osseous

  10. Facile nucleophilic fluorination reactions using tert-alcohols as a reaction medium: significantly enhanced reactivity of alkali metal fluorides and improved selectivity.

    PubMed

    Kim, Dong Wook; Jeong, Hwan-Jeong; Lim, Seok Tae; Sohn, Myung-Hee; Katzenellenbogen, John A; Chi, Dae Yoon

    2008-02-01

    Although protic solvents are generally not preferred for nucleophilic displacement reactions because of their partial positive charge and hydrogen-bonding capacity that solvate the nucleophile and reduce its reactivity, we recently reported a remarkably beneficial effect of using tertiary alcohols as a reaction media for nucleophilic fluorination with alkali metal fluorides, as well as fluorine-18 radiolabeling with [18F]fluoride ion for the preparation of PET radiopharmaceuticals. In this work, we investigate further the influence of the tert-alcohol reaction medium for nucleophilic fluorination with alkali metal fluorides by studying various interactions among tert-alcohols, the alkali metal fluoride (CsF), and the sulfonyloxy substrate. Factors such as hydrogen bonding between CsF and the tert-alcohol solvent, the formation of a tert-alcohol solvated fluoride, and hydrogen bonding between the sulfonate leaving group and the tert-alcohol appear to contribute to the dramatic increase in the rate of the nucleophilic fluorination reaction in the absence of any kind of catalyst. We found that fluorination of 1-(2-mesyloxyethyl)naphthalene (5) and N-5-bromopentanoyl-3,4-dimethoxyaniline (8) with Bu(4)N(+)F(-) in a tert-alcohol afforded the corresponding fluoro products in much higher yield than obtained by the conventional methods using dipolar aprotic solvents. The protic medium also suppresses formation of byproducts, such as alkenes, ethers, and cyclic adducts.

  11. PRECIPITATION OF URANIUM PEROXIDE OF LOW FLUORIDE CONTENT FROM SOLUTIONS CONTAINING FLUORIDES

    DOEpatents

    King, E.J.; Clark, H.M.

    1958-08-12

    S>A method is described for the preparation of fluoride free uraniunn peroxide precipitates, even though the solution from which the precipitation is made is contaminated with fluorides. This is accomplished by add ing aluminum ions to the solution, where they complex any fluoride present and prevent its precipitation with the uramum peroxide.

  12. Assessment of Amino Acid/Drug Transporters for Renal Transport of [18F]Fluciclovine (anti-[18F]FACBC) in Vitro

    PubMed Central

    Ono, Masahiro; Baden, Atsumi; Okudaira, Hiroyuki; Kobayashi, Masato; Kawai, Keiichi; Oka, Shuntaro; Yoshimura, Hirokatsu

    2016-01-01

    [18F]Fluciclovine (trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid; anti-[18F]FACBC), a positron emission tomography tracer used for the diagnosis of recurrent prostate cancer, is transported via amino acid transporters (AATs) with high affinity (Km: 97–230 μM). However, the mechanism underlying urinary excretion is unknown. In this study, we investigated the involvement of AATs and drug transporters in renal [18F]fluciclovine reuptake. [14C]Fluciclovine (trans-1-amino-3-fluoro[1-14C]cyclobutanecarboxylic acid) was used because of its long half-life. The involvement of AATs in [14C]fluciclovine transport was measured by apical-to-basal transport using an LLC-PK1 monolayer as model for renal proximal tubules. The contribution of drug transporters herein was assessed using vesicles/cells expressing the drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance-associated protein 4 (MRP4), organic anion transporter 1 (OAT1), organic anion transporter 3 (OAT3) , organic cation transporter 2 (OCT2), organic anion transporting polypeptide 1B1 (OATP1B1), and organic anion transporting polypeptide 1B3 (OATP1B3). The apical-to-basal transport of [14C]fluciclovine was attenuated by l-threonine, the substrate for system alanine-serine-cysteine (ASC) AATs. [14C]Fluciclovine uptake by drug transporter-expressing vesicles/cells was not significantly different from that of control vesicles/cells. Fluciclovine inhibited P-gp, MRP4, OAT1, OCT2, and OATP1B1 (IC50 > 2.95 mM). Therefore, system ASC AATs may be partly involved in the renal reuptake of [18F]fluciclovine. Further, given that [18F]fluciclovine is recognized as an inhibitor with millimolar affinity for the tested drug transporters, slow urinary excretion of [18F]fluciclovine may be mediated by system ASC AATs, but not by drug transporters. PMID:27754421

  13. Effects of fluoride-ion-implanted titanium surface on the cytocompatibility in vitro and osseointegatation in vivo for dental implant applications.

    PubMed

    Wang, Xue-jin; Liu, Hui-ying; Ren, Xiang; Sun, Hui-yan; Zhu, Li-ying; Ying, Xiao-xia; Hu, Shu-hai; Qiu, Ze-wen; Wang, Lang-ping; Wang, Xiao-feng; Ma, Guo-wu

    2015-12-01

    As an attractive technique for the improvement of biomaterials, Plasma immersion ion implantation (PIII) has been applied to modifying the titanium material for dental implant application. The present study investigated the cytocompatibility and early osseointegration of fluoride-ion-implanted titanium (F-Ti) surface and implants, both characterizing in their composition of titanium oxide and titanium fluoride. The cytocompatibility of F-Ti was evaluated in vitro by using scanning electron microscope, Cell Counting Kit-8 assay, alkaline phosphatase activity assay, and quantitative real-time polymerase chain reaction. The results showed that the F-Ti weakened the effects that Porphyromonas gingivalis exerted on the MG-63 cells in terms of morphology, proliferation, differentiation, and genetic expression when MG-63 cells and Porphyromonas gingivalis were co-cultured on the surface of F-Ti. Meanwhile, the osteogenic activity of F-Ti implants was assessed in vivo via evaluating the histological morphology and estimating histomorphometric parameters. The analysis of toluidine blue staining indicated that the new bone was more mature in subjects with F-Ti group, which exhibited the Haversian system, and the mean bone-implant contact value of F-Ti group was slightly higher than that of cp-Ti group (p>0.05). Fluorescence bands were wider and brighter in the F-Ti group, and the intensity of fluorochromes deposited at the sites of mineralized bone formation was significantly higher for F-Ti surfaces than for cp-Ti surfaces, within the 2nd, 3rd and 4th weeks (p<0.05). An indication is that the fluoride modified titanium can promote cytocompatibility and early osseointegration, thus providing a promising alternative for clinical use.

  14. The key role of the composition and structural features in fluoride ion conductivity in tysonite Ce1-xSrxF3-x solid solutions.

    PubMed

    Dieudonné, Belto; Chable, Johann; Body, Monique; Legein, Christophe; Durand, Etienne; Mauvy, Fabrice; Fourcade, Sébastien; Leblanc, Marc; Maisonneuve, Vincent; Demourgues, Alain

    2017-03-14

    Pure tysonite-type Ce1-xSrxF3-x solid solutions for 0 ≤ x < 0.15 were prepared by a solid-state route at 900 °C. The cell parameters follow Vegard's laws for 0 ≤ x ≤ 0.10 and the solubility limit is identified (0.10 < xlimit < 0.15). For 0 ≤ x ≤ 0.05, the F2-(Ce,Sr) and F3-(Ce,Sr) bond distances into [Ce1-xSrxF]((2-x)+) slabs strongly vary with x. This slab buckling is maximum around x = 0.025 and strongly affects the more mobile F1 fluoride ions located between the slabs. The (19)F MAS NMR spectra show the occurrence of F1-F2,3 exchange at 64 °C. The fraction of mobile F2,3 atoms deduced from the relative intensity of the NMR resonance is maximum for Ce0.99Sr0.01F2.99 (22% at 64 °C) while this fraction linearly increases with x for La1-xAExF3-x (AE = Ba, Sr). The highest conductivity found for Ce0.975Sr0.025F2.975 (3 × 10(-4) S cm(-1) at RT, Ea = 0.31 eV) is correlated to the largest dispersion of F2-(Ce,Sr) and F3-(Ce,Sr) distances which induces the maximum sheet buckling. Such a relationship between composition, structural features and fluoride ion conductivity is extended to other tysonite-type fluorides. The key role of the difference between AE(2+) and RE(3+) ionic radii and of the thickness of the slab buckling is established and could allow designing new ionic conductors.

  15. Early identification of antigen-specific immune responses in vivo by [18F]-labeled 3'-fluoro-3'-deoxy-thymidine ([18F]FLT) PET imaging.

    PubMed

    Aarntzen, Erik H J G; Srinivas, Mangala; De Wilt, Johannes H W; Jacobs, Joannes F M; Lesterhuis, W Joost; Windhorst, Albert D; Troost, Esther G; Bonenkamp, Johannes J; van Rossum, Michelle M; Blokx, Willeke A M; Mus, Roel D; Boerman, Otto C; Punt, Cornelis J A; Figdor, Carl G; Oyen, Wim J G; de Vries, I Jolanda M

    2011-11-08

    Current biomarkers are unable to adequately predict vaccine-induced immune protection in humans with infectious disease or cancer. However, timely and adequate assessment of antigen-specific immune responses is critical for successful vaccine development. Therefore, we have developed a method for the direct assessment of immune responses in vivo in a clinical setting. Melanoma patients with lymph node (LN) metastases received dendritic cell (DC) vaccine therapy, injected intranodally, followed by [(18)F]-labeled 3'-fluoro-3'-deoxy-thymidine ([(18)F]FLT) PET at varying time points after vaccination. Control LNs received saline or DCs without antigen. De novo immune responses were readily visualized in treated LNs early after the prime vaccination, and these signals persisted for up to 3 wk. This selective [(18)F]FLT uptake was markedly absent in control LNs, although tracer uptake in treated LNs increased profoundly with as little as 4.5 × 10(5) DCs. Immunohistochemical staining confirmed injected DC dispersion to T-cell areas and resultant activation of CD4(+) and CD8(+) T cells. The level of LN tracer uptake significantly correlates to the level of circulating antigen-specific IgG antibodies and antigen-specific proliferation of T cells in peripheral blood. Furthermore, this correlation was not observed with [(18)F]-labeled fluoro-2-deoxy-2-D-glucose. Therefore, [(18)F]FLT PET offers a sensitive tool to study the kinetics, localization, and involvement of lymphocyte subsets in response to vaccination. This technique allows for early discrimination of responding from nonresponding patients in anti-cancer vaccination and aid physicians in individualized decisionmaking.

  16. A Study of Mechanochemical Doping of Fluoride Crystals with a Fluorite Structure by Er3+ Ions via Electron Paramagnetic Resonance Spectra

    NASA Astrophysics Data System (ADS)

    Irisova, I. A.; Rodionov, A. A.; Tayurskii, D. A.; Yusupov, R. V.

    2014-05-01

    Using electron paramagnetic resonance (EPR) spectroscopy, we have shown that, upon mecha- noactivated doping of powders of compounds CaF2, SrF2, and BaF2 with Er3+ ions, impurity centers of single erbium ions with cubic symmetry are formed. Investigations of dependences of EPR spectra intensities on the particle size show that the process of mechanochemical doping with Er3+ ions proceeds differently for CaF2, SrF2, and BaF2 host matrices. In the case of CaF2, impurity centers are localized in a very thin near-surface layer of CaF2 particles, in SrF2, the impurity is distributed over the volume of particles, while, in BaF2, there is a layer of a finite thickness for which the probability of doping in the course of mechanosynthesis is very small and the impurity of the rare-earth element is localized in the core of large particles. These data can be explained assuming that the result of mechanosynthesis of particles of fluorides with a fluorite structure doped with Er3+ ions at room temperature is governed by two processes—mechanoactivated diffusion of rare-earth ions into particles and segregation of impurity ions at grain boundaries. In this case, the typical scales for compounds CaF2, SrF2, and BaF2 considerably differ from each other.

  17. Reference Tissue-Based Kinetic Evaluation of 18F-AV-1451 for Tau Imaging.

    PubMed

    Baker, Suzanne L; Lockhart, Samuel N; Price, Julie C; He, Mark; Huesman, Ronald H; Schonhaut, Daniel; Faria, Jamie; Rabinovici, Gil; Jagust, William J

    2017-02-01

    The goal of this paper was to evaluate the in vivo kinetics of the novel tau-specific PET radioligand (18)F-AV-1451 in cognitively healthy control (HC) and Alzheimer disease (AD) subjects, using reference region analyses.

  18. (18)F-fluoromisonidazole (FMISO) PET may have the potential to detect cardiac sarcoidosis.

    PubMed

    Manabe, Osamu; Hirata, Kenji; Shozo, Okamoto; Shiga, Tohru; Uchiyama, Yuko; Kobayashi, Kentaro; Watanabe, Shiro; Toyonaga, Takuya; Kikuchi, Hisaya; Oyama-Manabe, Noriko; Tamaki, Nagara

    2017-02-01

    (18)F-fluoromisonidazole (FMISO) is a positron emission tomography (PET) tracer that accumulates in hypoxic tissues. We here present a case of suspected cardiac sarcoidosis which was detected with increased FMISO uptake.

  19. Process for the production of 5'-deoxy-5-(/sup 18/F)fluorouridine

    DOEpatents

    Shiue, C.Y.; Wolf, A.P.; Friedkin, M.

    1983-08-10

    Process for the production of 5'-deoxy-5-fluorouridine and the corresponding /sup 18/F compound by the reaction of fluorine or acetyl hypofluorite with 2', 3'-di-O-acetyl-5'-deoxyuridine followed by hydrolysis.

  20. Non-invasive assessment of Alzheimer's disease neurofibrillary pathology using 18F-THK5105 PET.

    PubMed

    Okamura, Nobuyuki; Furumoto, Shozo; Fodero-Tavoletti, Michelle T; Mulligan, Rachel S; Harada, Ryuichi; Yates, Paul; Pejoska, Svetlana; Kudo, Yukitsuka; Masters, Colin L; Yanai, Kazuhiko; Rowe, Christopher C; Villemagne, Victor L

    2014-06-01

    Non-invasive imaging of tau pathology in the living brain would be useful for accurately diagnosing Alzheimer's disease, tracking disease progression, and evaluating the treatment efficacy of disease-specific therapeutics. In this study, we evaluated the clinical usefulness of a novel tau-imaging positron emission tomography tracer 18F-THK5105 in 16 human subjects including eight patients with Alzheimer's disease (three male and five females, 66-82 years) and eight healthy elderly controls (three male and five females, 63-76 years). All participants underwent neuropsychological examination and 3D magnetic resonance imaging, as well as both 18F-THK5105 and 11C-Pittsburgh compound B positron emission tomography scans. Standard uptake value ratios at 90-100 min and 40-70 min post-injection were calculated for 18F-THK5105 and 11C-Pittsburgh compound B, respectively, using the cerebellar cortex as the reference region. As a result, significantly higher 18F-THK5105 retention was observed in the temporal, parietal, posterior cingulate, frontal and mesial temporal cortices of patients with Alzheimer's disease compared with healthy control subjects. In patients with Alzheimer's disease, the inferior temporal cortex, which is an area known to contain high densities of neurofibrillary tangles in the Alzheimer's disease brain, showed prominent 18F-THK5105 retention. Compared with high frequency (100%) of 18F-THK5105 retention in the temporal cortex of patients with Alzheimer's disease, frontal 18F-THK5105 retention was less frequent (37.5%) and was only observed in cases with moderate-to-severe Alzheimer's disease. In contrast, 11C-Pittsburgh compound B retention was highest in the posterior cingulate cortex, followed by the ventrolateral prefrontal, anterior cingulate, and superior temporal cortices, and did not correlate with 18F-THK5105 retention in the neocortex. In healthy control subjects, 18F-THK5105 retention was ∼10% higher in the mesial temporal cortex than in the

  1. Aquifer wise seasonal variations and spatial distribution of major ions with focus on fluoride contamination-Pandharkawada block, Yavatmal district, Maharashtra, India.

    PubMed

    Pandith, Madhnure; Malpe, D B; Rao, A D; Rao, P N

    2016-02-01

    Seasonal variations in groundwater reveal lesser concentrations of major ions except NO3(-) during post-monsoon seasons in shallow aquifers as compared to deeper aquifers. The F(-) concentration from deeper aquifers is high in both seasons and shows a moderate positive relationship with weathering depth and is >5 mg/L in compound lava flow. Groundwater is mainly a Ca-HCO3 type in shallow aquifers and mixed type in deeper aquifers. Fluoride shows a positive correlation with pH, Na(+), HCO3(-) in shallow aquifers and an inverse correlation with Ca(2+) and HCO3(-) from deeper aquifers in both seasons. Approximately 45% of the samples are not suitable for drinking from both aquifers but suitable for irrigation purposes. Rock-water interaction, moderate alkalinity, sluggish movement, and higher residence time are the main causes for high F(-) in deeper aquifers as compared to shallow aquifers. As recommendations, drinking water requirement may be met from shallow aquifers/surface water and fluoride rich groundwater for other purposes. Most effective defluoridation techniques like ion exchange and reverse osmosis may be adopted along with integrated fluorosis mitigation measures and rooftop rainwater harvesting. Supplementary calcium and phosphorous rich food should be provided to children and creating awareness about safe drinking water habits, side effects of high F(-), and NO3(-) rich groundwater, improving oral hygiene conditions are other measures.

  2. Measurement of the 17 O(p,γ)18F reaction rate at astrophysically relevant energies

    NASA Astrophysics Data System (ADS)

    Hager, U.; Buchmann, L.; Davids, B.; Fallis, J.; Fulton, B. R.; Galinski, N.; Greife, U.; Hutcheon, D. A.; Ottewell, D.; Rojas, A.; Ruiz, C.; Setoodehnia, K.

    2012-03-01

    The 17O(p,γ)18F reaction plays an important role in hydrogen-burning nucleosynthesis. Conflicting values for the low-energy behavior of its cross section exist in the literature. We present direct measurements of the astrophysical S factor of the 17O(p,γ)18F reaction at center-of-mass energies between 250 and 500 keV. These measurements were conducted in inverse kinematics at the DRAGON recoil separator.

  3. Process for the production of .sup.18 F-2-deoxy-2-fluoro-D-glucose

    DOEpatents

    Elmaleh, David R.; Levy, Shlomo; Shiue, Chyng-Yann; Wolf, Alfred P.

    1986-01-01

    Process for the production of 2-deoxy-2-fluoro-D-glucose and the corresponding .sup.18 F-compound in which methyl 4,6-O-benzylidine-3-O-methyl-2-O-trifluoromethanesulfonyl-.beta.-D-mannopy ranoside is reacted with a triflating reagent, the resulting compound reacted with CsHF.sub.2, RbF or the corresponding .sup.18 F-compounds, and thereafter the alkyl groups removed by hydrolysis.

  4. Incidental Detection of Femoral Pseudoaneurysm at 18F-FDG PET/CT

    PubMed Central

    Nougaret, Stephanie; Ragucci, Monica; Bach, Ariadne M.; Carollo, Gabriella; Mannelli, Lorenzo

    2016-01-01

    A 72-year-old man with history of lung cancer and melanoma was referred for routine follow-up with 18F-FDG PET/CT. CT images showed a new mass in the right groin associated with mild FDG activity on 18F-FDG PET images. Subsequent ultrasound obtained the same day demonstrated flow within the lesion to be a pseudoaneurysm of the right femoral artery. PMID:26462043

  5. Lateralisation of striatal function: evidence from 18F-dopa PET in Parkinson's disease

    PubMed Central

    Cheesman, A; Barker, R; Lewis, S; Robbins, T; Owen, A; Brooks, D

    2005-01-01

    Objectives: The aetiology of the cognitive changes seen in Parkinson's disease (PD) is multifactorial but it is likely that a significant contribution arises from the disruption of dopaminergic pathways. This study aimed to investigate the contribution of the dopaminergic system to performance on two executive tasks using 18F-6-fluorodopa positron emission tomography (18F-dopa PET) in PD subjects with early cognitive changes. Methods: 16 non-demented, non-depressed PD subjects were evaluated with the Tower of London (TOL) spatial planning task, a verbal working memory task (VWMT) and 18F-dopa PET, all known to be affected in early PD. Statistical parametric mapping (SPM) localised brain regions in which 18F-dopa uptake covaried with performance scores. Frontal cortical resting glucose metabolism was assessed with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET. Results: SPM localised significant covariation between right caudate 18F-dopa uptake (Ki) and TOL scores and between left anterior putamen Ki and VWMT performance. No significant covariation was found between task scores and 18F-dopa Ki values in either limbic or cortical regions. Frontal cortical glucose metabolism was preserved in all cases. Conclusions: These findings support a causative role of striatal dopaminergic depletion in the early impairment of executive functions seen in PD. They suggest that spatial and verbal executive tasks require integrity of the right and left striatum, respectively, and imply that the pattern of cognitive changes manifest by a patient with PD may reflect differential dopamine loss in the two striatal complexes. PMID:16107352

  6. Parametric Binding Images of the TSPO Ligand 18F-DPA-714.

    PubMed

    Golla, Sandeep S V; Boellaard, Ronald; Oikonen, Vesa; Hoffmann, Anja; van Berckel, Bart N M; Windhorst, Albert D; Virta, Jere; Te Beek, Erik T; Groeneveld, Geert Jan; Haaparanta-Solin, Merja; Luoto, Pauliina; Savisto, Nina; Solin, Olof; Valencia, Ray; Thiele, Andrea; Eriksson, Jonas; Schuit, Robert C; Lammertsma, Adriaan A; Rinne, Juha O

    2016-10-01

    (18)F-labeled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide (DPA-714) is a radioligand for the 18-kDa translocator protein. The purpose of the present study was to identify the best method for generating quantitative parametric images of (18)F-DPA-714 binding.

  7. An improved strategy for the synthesis of [18F]-labeled arabinofuranosyl nuclosides

    PubMed Central

    Zhang, Hanwen; Cantorias, Melchor V.; Pillarsetty, NagaVaraKishore; Burnazi, Eva M.; Cai, Shangde; Lewis, Jason S.

    2012-01-01

    The expression of the herpes simplex virus type-1 thymidine kinase (HSV1-tk) gene can be imaged efficaciously using a variety of 2′-[18F]fluoro-2′-deoxy-1-b-D-arabinofuranosyl-uracil derivatives [[18F]-FXAU, X= I(iodo), E(ethyl), and M(methyl)]. However, the application of these derivatives in clinical and translational studies has been impeded by their complicated and long syntheses (3–5 h). To remedy these issues, in the study at hand we have investigated whether microwave or combined catalysts could facilitate the coupling reaction between sugar and nucleobase and, further, have probed the feasibility of establishing a novel approach for [18F]-FXAU synthesis. We have demonstrated that the rate of the trimethylsilyl trifluoromethanesulfonate (TMSOTf)-catalyzed coupling reaction between the 2-deoxy-sugar and uracil derivatives at 90°C can be significantly accelerated by microwave-driven heating or by the addition of Lewis acid catalyst (SnCl4). Further, we have observed that the stability of the α- and β-anomers of [18F]-FXAU derivatives differs during the hydrolysis step. Using the microwave-driven heating approach, overall decay-corrected radiochemical yields of 19–27% were achieved for [18F]-FXAU in 120 min at a specific activity of >22 MBq/nmol (595 Ci/mmol). Ultimately, we believe that these high yielding syntheses of [18F]-FIAU, [18F]-FMAU and [18F]-FEAU will facilitate routine production for clinical applications. PMID:22819195

  8. Action of selected agents on the accumulation of /sup 18/F by Streptococcus mutans

    SciTech Connect

    Yotis, W.W.; Zeb, M.; Brennan, P.C.; Kirchner, F.R.; Glendenin, L.E.; Wu-Yuan, C.D.

    1983-01-01

    The action of certain substances known to induce cellular alterations, or encountered in the oral cavity, on the accumulation of /sup 18/F by Streptococcus mutans GS-5 has been investigated. A 62-67% inhibition in the number of /sup 18/F atoms bound per mg dry weight of cells could be induced by a 15 min pretreatment with 2.7 x 10/sup -4/ M cetyltrimethylammoniumbromide, 1 x 10/sup -1/ M acetic anhydride, or 7 x 10/sup -2/ M HCl. Plate counts indicated that alteration of the cellular composition rather than viability was responsible for this diminution in /sup 18/F accumulation. Prior exposure for 15 min of this organism to 1 M HCHO or 0.1 M NaOH did not alter /sup 18/F accumulation. Of the common salts encountered in the oral cavity, CaCl/sub 2/ enhanced /sup 18/F binding. Pretreatment of the assay cells for 15-160 min with 0.1 mg/ml of trypsin, pronase, protease, ..cap alpha..-glucosidase, dextranase, or lactoferrin had no significant effect on the accumulation of /sup 18/. However, pre-exposure of cells for 60 min to 1-10 mg/ml of either amylase or lipase induced a 40-67% inhibition in the binding of /sup 18/F, while lysozyme enhanced the binding of /sup 18/F by the cells. It would appear then that the binding of /sup 18/F by S. mutans may be altered by certain substances encountered in the oral cavity. 17 references, 1 figure, 5 tables.

  9. Simplified one-pot synthesis of [.sup.18F]SFB for radiolabeling

    DOEpatents

    Olma, Sebastian; Shen, Clifton Kwang-Fu

    2015-08-04

    A non-aqueous single pot synthesis of [.sup.18F]SFB is set forth. The [.sup.18F]SFB produced with this method is then used, for example, to label a peptide or an engineered antibody fragment (diabody) targeting human epidermal growth factor receptor 2 (HER2) as representative examples of labeled compounds for use as an injectable composition to locate abnormal tissue, specifically tumors within an animal or human using a PET scan.

  10. Simplified one-pot synthesis of [.sup.18F]SFB for radiolabeling

    DOEpatents

    Olma, Sebastian; Shen, Clifton Kwang-Fu

    2013-07-16

    A non-aqueous single pot synthesis of [.sup.18F]SFB is set forth. The [.sup.18F]SFB produced with this method is then used, for example, to label a peptide or an engineered antibody fragment (diabody) targeting human epidermal growth factor receptor 2 (HER2) as representative examples of labeled compounds for use as an injectable composition to locate abnormal tissue, specifically tumors within an animal or human using a PET scan.

  11. [(18)F]FDG PET signal is driven by astroglial glutamate transport.

    PubMed

    Zimmer, Eduardo R; Parent, Maxime J; Souza, Débora G; Leuzy, Antoine; Lecrux, Clotilde; Kim, Hyoung-Ihl; Gauthier, Serge; Pellerin, Luc; Hamel, Edith; Rosa-Neto, Pedro

    2017-03-01

    Contributions of glial cells to neuroenergetics have been the focus of extensive debate. Here we provide positron emission tomography evidence that activation of astrocytic glutamate transport via the excitatory amino acid transporter GLT-1 triggers widespread but graded glucose uptake in the rodent brain. Our results highlight the need for a reevaluation of the interpretation of [(18)F]FDG positron emission tomography data, whereby astrocytes would be recognized as contributing to the [(18)F]FDG signal.

  12. Imaging Enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography

    PubMed Central

    Weinstein, Edward A.; Ordonez, Alvaro A.; DeMarco, Vincent P.; Murawski, Allison M.; Pokkali, Supriya; MacDonald, Elizabeth M.; Klunk, Mariah; Mease, Ronnie C.; Pomper, Martin G.; Jain, Sanjay K.

    2015-01-01

    The Enterobacteriaceae are a family of rod-shaped Gram-negative bacteria that normally inhabit the gastrointestinal tract and are the most common cause of Gram-negative bacterial infections in humans. In addition to causing serious multidrug-resistant, hospital-acquired infections, a number of Enterobacteriaceae species are also recognized as biothreat pathogens. As a consequence, new tools are urgently needed to specifically identify and localize infections due to Enterobacteriaceae and to monitor antimicrobial efficacy. In this report, we used commercially available 2-[18F]-fluorodeoxyglucose (18F-FDG) to produce 2-[18F]-fluorodeoxysorbitol (18F-FDS), a radioactive probe for Enterobacteriaceae, in 30 min. 18F-FDS selectively accumulated in Enterobacteriaceae, but not in Gram-positive bacteria or healthy mammalian or cancer cells in vitro. In a murine myositis model, 18F-FDS positron emission tomography (PET) rapidly differentiated true infection from sterile inflammation with a limit of detection of 6.2 ± 0.2 log10 colony-forming units (CFU) for Escherichia coli. Our findings were extended to models of mixed Gram-positive and Gram-negative thigh co-infections, brain infection, Klebsiella pneumonia, and mice undergoing immunosuppressive chemotherapy. This technique rapidly and specifically localized infections due to Enterobacteriaceae, providing a three-dimensional holistic view within the animal. Last, 18F-FDS PET monitored the efficacy of antimicrobial treatment, demonstrating a PET signal proportionate to the bacterial burden. Therapeutic failures associated with multidrug-resistant, extended-spectrum β-lactamase (ESBL)–producing E. coli infections were detected in real time. Together, these data show that 18F-FDS is a candidate imaging probe for translation to human clinical cases of known or suspected infections owing to Enterobacteriaceae. PMID:25338757

  13. Amyloid deposition after cerebral hypoperfusion: evidenced on [(18)F]AV-45 positron emission tomography.

    PubMed

    Huang, Kuo-Lun; Lin, Kun-Ju; Ho, Meng-Yang; Chang, Yeu-Jhy; Chang, Chien-Hung; Wey, Shiaw-Pyng; Hsieh, Chia-Ju; Yen, Tzu-Chen; Hsiao, Ing-Tsung; Lee, Tsong-Hai

    2012-08-15

    Animal studies have shown that cerebral hypoperfusion may be associated with amyloid plaque accumulation. Amyloid plaque is known to be associated with dementia and [(18)F]AV-45 is a positron emission tomography (PET) ligand that binds to extracelluar plaques. We hypothesized that demented patients with cerebral hypoperfusion may have increased [(18)F]AV-45 uptake. Five demented patients with cerebral hypoperfusion due to unilateral carotid artery stenosis (CAS) were examined with [(18)F]AV-45 PET, and the results were compared with six elderly controls. The standard uptake value ratio (SUVR) of each region of interest (ROI) was created using whole cerebellum as the reference region. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information. Patients with dementia and unilateral CAS had a higher global [(18)F]AV-45 SUVR (1.34 ± 0.06) as compared with controls (1.10 ± 0.04, p=0.0043), especially over the frontal, temporal, precuneus, anterior cingulate and occipital regions. The statistical distribution maps revealed a significantly increased [(18)F]AV-45 SUVR in the medial frontal, caudate, thalamus, posterior cingulate, occipital and middle and superior temporal regions ipsilateral to the side of CAS (p<0.01). The present study found that cerebral [(18)F]AV-45 binding is increased in demented patients with CAS, and its distribution is lateralized to the CAS side, suggesting that amyloid-related dementia may occur under cerebral hypoperfusion.

  14. Intra-individual comparison of 18F-FET and 18F-DOPA in PET imaging of recurrent brain tumors

    PubMed Central

    Kratochwil, Clemens; Combs, Stephanie E.; Leotta, Karin; Afshar-Oromieh, Ali; Rieken, Stefan; Debus, Jürgen; Haberkorn, Uwe; Giesel, Frederik L.

    2014-01-01

    Background Both 18F-fluorodihydroxyphenylalanine (18F-DOPA) and 18F-fluoroethyltyrosine (18F-FET) have already been used successfully for imaging of brain tumors. The aim of this study was to evaluate differences between these 2 promising tracers to determine the consequences for imaging protocols and the interpretation of findings. Methods Forty minutes of dynamic PET imaging were performed on 2 consecutive days with both 18F-DOPA and 18F-FET in patients with recurrent low-grade astrocytoma (n = 8) or high-grade glioblastoma (n = 8). Time-activity-curves (TACs), standardized uptake values (SUVs) and compartment modeling of both tracers were analyzed, respectively. Results The TAC of DOPA-PET peaked at 8 minutes p.i. with SUV 5.23 in high-grade gliomas and 10 minutes p.i. with SUV 4.92 in low-grade gliomas. FET-PET peaked at 9 minutes p.i. with SUV 3.17 in high-grade gliomas and 40 minutes p.i. with SUV 3.24 in low-grade gliomas. Neglecting the specific uptake of DOPA into the striatum, the tumor-to-brain and tumor-to-blood ratios were higher for DOPA-PET. Kinetic modeling demonstrated a high flow constant k1 (mL/ccm/min), representing cellular internalization through AS-transporters, for DOPA in both high-grade (k1 = 0.59) and low-grade (k1 = 0.55) tumors, while lower absolute values and a relevant dependency from tumor-grading (high-grade k1 = 0.43; low-grade k1 = 0.33) were observed with FET. Conclusions DOPA-PET demonstrates superior contrast ratios for lesions outside the striatum, but SUVs do not correlate with grading. FET-PET can provide additional information on tumor grading and benefits from lower striatal uptake but presents lower contrast ratios and requires prolonged imaging if histology is not available in advance due to a more variable time-to-peak. PMID:24305717

  15. (18)F-FET PET Uptake Characteristics in Patients with Newly Diagnosed and Untreated Brain Metastasis.

    PubMed

    Unterrainer, Marcus; Galldiks, Norbert; Suchorska, Bogdana; Kowalew, Lara-Caroline; Wenter, Vera; Schmid-Tannwald, Christine; Niyazi, Maximilian; Bartenstein, Peter; Langen, Karl-Josef; Albert, Nathalie L

    2017-04-01

    In patients with brain metastasis, PET using labeled amino acids has gained clinical importance, mainly regarding the differentiation of viable tumor tissue from treatment-related effects. However, there is still limited knowledge concerning the uptake characteristics in patients with newly diagnosed and untreated brain metastases. Hence, we evaluated the uptake characteristics in these patients using dynamic O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) PET. Methods: Patients with newly diagnosed brain metastases without prior local therapy and (18)F-FET PET scanning were retrospectively identified in 2 centers. Static and dynamic PET parameters (maximal/mean tumor-to-brain-ratio [TBRmax/TBRmean], biologic tumor volume [BTV], and time-activity curves with minimal time to peak [TTPmin]) were evaluated and correlated with MRI parameters (maximal lesion diameter, volume of contrast enhancement) and originating primary tumor. Results: Forty-five brain metastases in 30 patients were included. Forty of 45 metastases (89%) had a TBRmax ≥ 1.6 and were classified as (18)F-FET-positive (median TBRmax, 2.53 [range, 1.64-9.47]; TBRmean, 1.86 [range, 1.63-5.48]; and BTV, 3.59 mL [range, 0.04-23.98 mL], respectively). In 39 of 45 brain metastases eligible for dynamic analysis, a wide range of TTPmin was observed (median, 22.5 min; range, 4.5-47.5 min). All (18)F-FET-negative metastases had a diameter of ≤ 1.0 cm, whereas metastases with a > 1.0 cm diameter all showed pathologic (18)F-FET uptake, which did not correlate with lesion size. The highest variability of uptake intensity was observed within the group of melanoma metastases. Conclusion: Untreated metastases predominantly show increased (18)F-FET uptake, and only a third of metastases < 1.0 cm were (18)F-FET-negative, most likely because of scanner resolution and partial-volume effects. In metastases > 1.0 cm, (18)F-FET uptake intensity was highly variable and independent of tumor size (even intraindividually). (18

  16. Beyond Conventional Cathode Materials for Lithium-ion Batteries and Sodium-ion Batteries Nickel fluoride conversion materials and P2 type Sodium-ion intercalation cathodes

    NASA Astrophysics Data System (ADS)

    Lee, Dae Hoe

    The Li-ion battery is one of the most important rechargeable energy storage devices due to its high energy density, long cycle life, and reliable safety. Although the performances of Li-ion batteries have been improved dramatically, the limit in terms of the energy density still needs to be resolved to meet the growing demands for large-scale mobile devices. Choosing the cathode material is the most pivotal issue in achieving higher energy, since the energy density is directly correlated to the specific capacity of the cathode. Intercalation-based cathode materials have been widely utilized in commercial products; however they yield a limited capacity due to restricted crystallographic sites for Li-ions. In this thesis, the NiF2 and NiO doped NiF2/C conversion materials, which display substantially greater capacities, are intensively studied using various synchrotron X-ray techniques and magnetic measurements. The enhanced electronic conductivity of NiO doped NiF2/C is associated with a significant improvement in the reversible conversion reaction. While bimodal Ni nanoparticles are maintained for NiO doped NiF2/C upon the discharge, for pure NiF2 only smaller nanoparticles remain following the 2nd discharge. Based on the electronic conductivity, it is demonstrated that the size of Ni nanoparticles is associated with the conversion kinetics and consequently the reversibility. Although Li-ion batteries offer the highest energy density among all the secondary batteries, the amount of the reserves and the cost associated with the Li sources are still a concern. In the second part of the thesis, P2 type Na2/3[Ni1/3Mn2/3]O2 is investigated to understand the structural stability in the Na-ion batteries. Significantly improved battery performances are obtained by excluding the phase transformation region. In addition, the structural evolution of the P2-Na0.8[Li0.12Ni0.22Mn0.66]O 2 is tracked by in situ technique and revealed no phase transformation during the cycling. It

  17. 123I-MIBG, 18F-DOPA and 18F-FDG in a patient with MEN2 syndrome and recurrent pheochromocytoma.

    PubMed

    Cuenca-Cuenca, J I; Marín-Oyaga, V A; Borrego-Dorado, I; Navarro-González, E; Martos-Martínez, J M; Vázquez-Albertino, R

    2013-01-01

    Pheochromocytoma is a rare tumor located in the medulla of the adrenal gland that is characterized by high catecholamine synthesis. Surgery is the treatment of choice and is usually curative if appropriately diagnosed and excised. Imaging methods, both morphological and functional, are of great importance in presurgical evaluation. We report the case of a female patient with multiple endocrine neoplasia syndrome type 2, with bilateral adrenalectomy due to two pheochromocytomas and progressive elevation of urinary metanephrine. Magnetic resonance imaging showed a nodular image in the right adrenal fossa. The patient was referred to our unit in order to confirm suspicion of recurrence. Due to the absence of pathological findings in the (123)I-MIBG scintigraphy and high suspicion of recurrence, PET/CT imaging with (18)F-DOPA and (18)F-FDG were performed, and the diagnosis was confirmed.

  18. Fluoride Content in Alcoholic Drinks.

    PubMed

    Goschorska, Marta; Gutowska, Izabela; Baranowska-Bosiacka, Irena; Rać, Monika Ewa; Chlubek, Dariusz

    2016-06-01

    The aim of the study was to determine the role of alcoholic drinks as a potential source of dietary fluoride by means of measuring fluoride levels in selected alcoholic drinks available on the Polish market that are also diverse in terms of the percentage content of ethanol. The study was conducted on 48 types of drinks with low, medium, and high alcohol content available on the Polish market and offered by various manufacturers, both Polish and foreign. Fluoride concentrations in individual samples were measured by potentiometric method with a fluoride ion-selective electrode. The highest fluoride levels were determined in the lowest percentage drinks (less than 10 % v/v ethanol), with the lowest fluoride levels observed in the highest percentage drinks (above 40 % v/v ethanol). In terms of types of alcoholic drinks, the highest fluoride levels were determined in beers and wines, while the lowest levels were observed in vodkas. These data confirm the fact that alcoholic beverages need to be considered as a significant source of fluoride delivered into the body.

  19. Divalent fluoride doped cerium fluoride scintillator

    DOEpatents

    Anderson, David F.; Sparrow, Robert W.

    1991-01-01

    The use of divalent fluoride dopants in scintillator materials comprising cerium fluoride is disclosed. The preferred divalent fluoride dopants are calcium fluoride, strontium fluoride, and barium fluoride. The preferred amount of divalent fluoride dopant is less than about two percent by weight of the total scintillator. Cerium fluoride scintillator crystals grown with the addition of a divalent fluoride have exhibited better transmissions and higher light outputs than crystals grown without the addition of such dopants. These scintillators are useful in radiation detection and monitoring applications, and are particularly well suited for high-rate applications such as positron emission tomography (PET).

  20. 18F-AV-1451 positron emission tomography in Alzheimer's disease and progressive supranuclear palsy.

    PubMed

    Passamonti, Luca; Vázquez Rodríguez, Patricia; Hong, Young T; Allinson, Kieren S J; Williamson, David; Borchert, Robin J; Sami, Saber; Cope, Thomas E; Bevan-Jones, W Richard; Jones, P Simon; Arnold, Robert; Surendranathan, Ajenthan; Mak, Elijah; Su, Li; Fryer, Tim D; Aigbirhio, Franklin I; O'Brien, John T; Rowe, James B

    2017-03-01

    The ability to assess the distribution and extent of tau pathology in Alzheimer's disease and progressive supranuclear palsy in vivo would help to develop biomarkers for these tauopathies and clinical trials of disease-modifying therapies. New radioligands for positron emission tomography have generated considerable interest, and controversy, in their potential as tau biomarkers. We assessed the radiotracer 18F-AV-1451 with positron emission tomography imaging to compare the distribution and intensity of tau pathology in 15 patients with Alzheimer's pathology (including amyloid-positive mild cognitive impairment), 19 patients with progressive supranuclear palsy, and 13 age- and sex-matched controls. Regional analysis of variance and a support vector machine were used to compare and discriminate the clinical groups, respectively. We also examined the 18F-AV-1451 autoradiographic binding in post-mortem tissue from patients with Alzheimer's disease, progressive supranuclear palsy, and a control case to assess the 18F-AV-1451 binding specificity to Alzheimer's and non-Alzheimer's tau pathology. There was increased 18F-AV-1451 binding in multiple regions in living patients with Alzheimer's disease and progressive supranuclear palsy relative to controls [main effect of group, F(2,41) = 17.5, P < 0.0001; region of interest × group interaction, F(2,68) = 7.5, P < 0.00001]. More specifically, 18F-AV-1451 binding was significantly increased in patients with Alzheimer's disease, relative to patients with progressive supranuclear palsy and with control subjects, in the hippocampus and in occipital, parietal, temporal, and frontal cortices (t's > 2.2, P's < 0.04). Conversely, in patients with progressive supranuclear palsy, relative to patients with Alzheimer's disease, 18F-AV-1451 binding was elevated in the midbrain (t = 2.1, P < 0.04); while patients with progressive supranuclear palsy showed, relative to controls, increased 18F-AV-1451 uptake in the putamen, pallidum

  1. In vivo imaging of neuromelanin in Parkinson's disease using 18F-AV-1451 PET.

    PubMed

    Hansen, Allan K; Knudsen, Karoline; Lillethorup, Thea P; Landau, Anne M; Parbo, Peter; Fedorova, Tatyana; Audrain, Hélène; Bender, Dirk; Østergaard, Karen; Brooks, David J; Borghammer, Per

    2016-07-01

    The tau tangle ligand (18)F-AV-1451 ((18)F-T807) binds to neuromelanin in the midbrain, and may therefore be a measure of the pigmented dopaminergic neuronal count in the substantia nigra. Parkinson's disease is characterized by progressive loss of dopaminergic neurons. Extrapolation of post-mortem data predicts that a ∼30% decline of nigral dopamine neurons is necessary to cause motor symptoms in Parkinson's disease. Putamen dopamine terminal loss at disease onset most likely exceeds that of the nigral cell bodies and has been estimated to be of the order of 50-70%. We investigated the utility of (18)F-AV-1451 positron emission tomography to visualize the concentration of nigral neuromelanin in Parkinson's disease and correlated the findings to dopamine transporter density, measured by (123)I-FP-CIT single photon emission computed tomography. A total of 17 patients with idiopathic Parkinson's disease and 16 age- and sex-matched control subjects had (18)F-AV-1451 positron emission tomography using a Siemens high-resolution research tomograph. Twelve patients with Parkinson's disease also received a standardized (123)I-FP-CIT single photon emission computed tomography scan at our imaging facility. Many of the patients with Parkinson's disease displayed visually apparent decreased (18)F-AV-1451 signal in the midbrain. On quantitation, patients showed a 30% mean decrease in total nigral (18)F-AV-1451 volume of distribution compared with controls (P = 0.004), but there was an overlap of the individual ranges. We saw no significant correlation between symptom dominant side and contralateral nigral volume of distribution. There was no correlation between nigral (18)F-AV-1451 volume of distribution and age or time since diagnosis. In the subset of 12 patients, who also had a (123)I-FP-CIT scan, the mean total striatal dopamine transporter signal was decreased by 45% and the mean total (18)F-AV-1451 substantia nigra volume of distribution was decreased by 33% after

  2. 18F-labeled FECNT: a selective radioligand for PET imaging of brain dopamine transporters.

    PubMed

    Goodman, M M; Kilts, C D; Keil, R; Shi, B; Martarello, L; Xing, D; Votaw, J; Ely, T D; Lambert, P; Owens, M J; Camp, V M; Malveaux, E; Hoffman, J M

    2000-01-01

    Fluorine-18 labeled 2beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(2-fluoroethyl)nort ropane (FECNT) was synthesized in the development of a dopamine transporter (DAT) imaging ligand for positron emission tomography (PET). The methods of radiolabeling and ligand synthesis of FECNT, and the results of the in vitro characterization and in vivo tissue distribution in rats and in vivo PET imaging in rhesus monkeys of [18F]FECNT are described. Fluorine-18 was introduced into 2beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(2-fluoroethyl)nort ropane (4) by preparation of 1-[18F]fluoro-2-tosyloxyethane (2) followed by alkylation of 2beta-carbomethoxy-3beta-(4-chlorophenyl)nortropane (3) in 21% radiochemical yield (decay corrected to end of bombardment [EOB]). Competition binding in cells stably expressing the transfected human DAT serotonin transporter (SERT) and norepinephrine transporter (NET) labeled by [3H]WIN 35428, [3H]citalopram, and [3H]nisoxetine, respectively, indicated the following order of DAT affinity: GBR 12909 > CIT > 2beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(3-fluoropropyl) nortropane (FPCT) > FECNT. The affinity of FECNT for SERT and NET was 25- and 156-fold lower, respectively, than for DAT. Blocking studies were performed in rats with a series of transporter-specific agents and demonstrated that the brain uptake of [18F]FECNT was selective and specific for DAT-rich regions. PET brain imaging studies in monkeys demonstrated high [18F]FECNT uptake in the caudate and putamen that resulted in caudate-to-cerebellum and putamen-to-cerebellum ratios of 10.5 at 60 min. [18F]FECNT uptake in the caudate/putamen peaked in less than 75 min and exhibited higher caudate- and putamen-to-cerebellum ratios at transient equilibrium than reported for 11C-WIN 35,428, [11C]CIT/RTI-55, or [18F]beta-CIT-FP. Analysis of monkey arterial plasma samples using high performance liquid chromatography determined that there was no detectable formation of lipophilic radiolabeled

  3. PET Cell Tracking Using 18F-FLT is Not Limited by Local Reuptake of Free Radiotracer

    PubMed Central

    MacAskill, Mark G.; Tavares, Adriana S.; Wu, Junxi; Lucatelli, Christophe; Mountford, Joanne C.; Baker, Andrew H.; Newby, David E.; Hadoke, Patrick W. F.

    2017-01-01

    Assessing the retention of cell therapies following implantation is vital and often achieved by labelling cells with 2′-[18F]-fluoro-2′-deoxy-D-glucose (18F-FDG). However, this approach is limited by local retention of cell-effluxed radiotracer. Here, in a preclinical model of critical limb ischemia, we assessed a novel method of cell tracking using 3′-deoxy-3′-L-[18F]-fluorothymidine (18F-FLT); a clinically available radiotracer which we hypothesise will result in minimal local radiotracer reuptake and allow a more accurate estimation of cell retention. Human endothelial cells (HUVECs) were incubated with 18F-FDG or 18F-FLT and cell characteristics were evaluated. Dynamic positron emission tomography (PET) images were acquired post-injection of free 18F-FDG/18F-FLT or 18F-FDG/18F-FLT-labelled HUVECs, following the surgical induction of mouse hind-limb ischemia. In vitro, radiotracer incorporation and efflux was similar with no effect on cell viability, function or proliferation under optimised conditions (5 MBq/mL, 60 min). Injection of free radiotracer demonstrated a faster clearance of 18F-FLT from the injection site vs. 18F-FDG (p ≤ 0.001), indicating local cellular uptake. Using 18F-FLT-labelling, estimation of HUVEC retention within the engraftment site 4 hr post-administration was 24.5 ± 3.2%. PET cell tracking using 18F-FLT labelling is an improved approach vs. 18F-FDG as it is not susceptible to local host cell reuptake, resulting in a more accurate estimation of cell retention. PMID:28287126

  4. Caged [(18)F]FDG Glycosylamines for Imaging Acidic Tumor Microenvironments Using Positron Emission Tomography.

    PubMed

    Flavell, Robert R; Truillet, Charles; Regan, Melanie K; Ganguly, Tanushree; Blecha, Joseph E; Kurhanewicz, John; VanBrocklin, Henry F; Keshari, Kayvan R; Chang, Christopher J; Evans, Michael J; Wilson, David M

    2016-01-20

    Solid tumors are hypoxic with altered metabolism, resulting in secretion of acids into the extracellular matrix and lower relative pH, a feature associated with local invasion and metastasis. Therapeutic and diagnostic agents responsive to this microenvironment may improve tumor-specific delivery. Therefore, we pursued a general strategy whereby caged small-molecule drugs or imaging agents liberate their parent compounds in regions of low interstitial pH. In this manuscript, we present a new acid-labile prodrug method based on the glycosylamine linkage, and its application to a class of positron emission tomography (PET) imaging tracers, termed [(18)F]FDG amines. [(18)F]FDG amines operate via a proposed two-step mechanism, in which an acid-labile precursor decomposes to form the common radiotracer 2-deoxy-2-[(18)F]fluoro-d-glucose, which is subsequently accumulated by glucose avid cells. The rate of decomposition of [(18)F]FDG amines is tunable in a systematic fashion, tracking the pKa of the parent amine. In vivo, a 4-phenylbenzylamine [(18)F]FDG amine congener showed greater relative accumulation in tumors over benign tissue, which could be attenuated upon tumor alkalinization using previously validated models, including sodium bicarbonate treatment, or overexpression of carbonic anhydrase. This new class of PET tracer represents a viable approach for imaging acidic interstitial pH with potential for clinical translation.

  5. Determining the optimal fluoride concentration in drinking water for fluoride endemic regions in South India.

    PubMed

    Viswanathan, Gopalan; Jaswanth, A; Gopalakrishnan, S; Siva Ilango, S; Aditya, G

    2009-10-01

    Fluoride ion in drinking water is known for both beneficial and detrimental effects on health. The prevalence of fluorosis is mainly due to the intake of large quantities of fluoride through drinking water owing to more than 90% bioavailability. The objective of this study is to predict optimal fluoride level in drinking water for fluoride endemic regions by comprising the levels of fluoride and other water quality parameters in drinking water, prevalence of fluorosis, fluoride intake through water, food and beverages such as tea and coffee and also considering the progressive accumulation of fluoride in animal bones, by comparing with non fluoride endemic areas comprise of the same geological features with the aid of regression analysis. Result of this study shows that increase of fluoride level above 1.33 mg/l in drinking water increases the community fluorosis index (CFI) value more than 0.6, an optimum index value above which fluorosis is considered to be a public health problem. Regression plot between water fluoride and bone fluoride levels indicates that, every increase of 0.5mg/l unit of water fluoride level increases the bone fluoride level of 52 mg/kg unit within 2 to 3 years. Furthermore, the consumption of drinking water containing more than 0.65 mg/l of fluoride can raise the total fluoride intake per day more than 4 mg, which is the optimum fluoride dose level recommended for adults by the Agency for Toxic Substances and Disease Registry. From the result, the people in fluoride endemic areas in South India are advised to consume drinking water with fluoride level within the limit of 0.5 to 0.65 mg/l to avoid further fluorosis risk.

  6. Water fluoridation and osteoporotic fracture.

    PubMed

    Hillier, S; Inskip, H; Coggon, D; Cooper, C

    1996-09-01

    Osteoporotic fractures constitute a major public health problem. These fractures typically occur at the hip, spine and distal forearm. Their pathogenesis is heterogeneous, with contributions from both bone strength and trauma. Water fluoridation has been widely proposed for its dental health benefits, but concerns have been raised about the balance of skeletal risks and benefits of this measure. Fluoride has potent effects on bone cell function, bone structure and bone strength. These effects are mediated by the incorporation of fluoride ions in bone crystals to form fluoroapatite, and through an increase in osteoblast activity. It is believed that a minimum serum fluoride level of 100 ng/ml must be achieved before osteoblasts will be stimulated. Serum levels associated with drinking water fluoridated to 1 ppm are usually several times lower than this value, but may reach this threshold at concentrations of 4 ppm in the drinking water. Animal studies suggest no effect of low-level (0-3 ppm) fluoride intake on bone strength, but a possible decrease at higher levels. Sodium fluoride has been used to treat established osteoporosis for nearly 30 years. Recent trials of this agent, prescribed at high doses, have suggested that despite a marked increase in bone mineral density, there is no concomitant reduction in vertebral fracture incidence. Furthermore, the increase in bone density at the lumbar spine may be achieved at the expense of bone mineral in the peripheral cortical skeleton. As a consequence, high dose sodium fluoride (80 mg daily) is not currently used to treat osteoporosis. At lower doses, recent trials have suggested a beneficial effect on both bone density and fracture. The majority of epidemiological evidence regarding the effect of fluoridated drinking water on hip fracture incidence is based on ecological comparisons. Although one Finnish study suggested that hip fracture rates in a town with fluoridated water were lower than those in a matching town

  7. Synthesis and Evaluation of Two 18F-Labeled 6-Iodo-2-(4′-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine Derivatives as Prospective Radioligands for β-Amyloid in Alzheimer’s Disease

    PubMed Central

    Cai, Lisheng; Chin, Frederick T.; Pike, Victor W.; Toyama, Hiroshi; Liow, Jeih-San; Zoghbi, Sami S.; Modell, Kendra; Briard, Emmanuelle; Shetty, H. Umesha; Sinclair, Kathryn; Donohue, Sean; Tipre, Dnyanesh; Kung, Mei-Ping; Dagostin, Claudio; Widdowson, David A.; Green, Michael; Gao, Weiyi; Herman, Mary M.; Ichise, Masanori; Innis, Robert B.

    2014-01-01

    This study evaluated 18F-labeled IMPY [6-iodo-2-(4′-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine] derivatives as agents for imaging β-amyloid plaque with positron emission tomography (PET). The precursor for radiolabeling and reference compounds was synthesized in up to five steps from commercially accessible starting materials. One of the two N-methyl groups of IMPY was substituted with either a 3-fluoropropyl (FPM-IMPY) or a 2-fluoroethyl (FEM-IMPY) group. FPM-IMPY and FEM-IMPY were found to have moderate affinity for Aβ- aggregates with Ki = 27 ± 8 and 40 ± 5 nM, respectively. A “one-pot” method for 18F-2-fluoroethylation and 18F-3-fluoropropylation of the precursor was developed. The overall decay-corrected radiochemical yields were 26–51%. In PET experiments with normal mouse, high uptake of activity was obtained in the brain after iv injection of each probe: 6.4% ID/g for [18F]FEM-IMPY at 1.2 min, and 5.7% ID/g for [18F]FPM-IMPY at 0.8 min. These values were similar to those of [123I/125I]IMPY (7.2% ID/g at 2 min). Polar and nonpolar radioactive metabolites were observed in both plasma and brain homogenates after injection of [18F]FEM or [18F]FPM-IMPY. In contrast to the single-exponential washout of [123I/125I]IMPY, the washouts of brain activity for the two fluorinated analogues were biphasic, with an initial rapid phase over 20 min and a subsequent much slower phase. Residual brain activity at 2 h, which may represent polar metabolites trapped in the brain, was 4.5% ID/g for [18F]FEM-IMPY and 2.1% ID/g for [18F]FPM-IMPY. Substantial skull uptake of [18F]fluoride was also clearly observed. With a view to slow the metabolism of [18F]FEM-IMPY, an analogue was prepared with deuteriums substituted for the four ethyl hydrogens. However, D4-[18F]FEM-IMPY showed the same brain uptake and clearance as the protio analogue. Metabolism of the [18F]FEM-IMPY was appreciably slower in rhesus monkey than in mouse. Autoradiography of postmortem brain sections

  8. One-step synthesis of 4-[(18) F]fluorobenzyltriphenylphosphonium cation for imaging with positron emission tomography.

    PubMed

    Zhang, Zhengxing; Zhang, Chengcheng; Lau, Joseph; Colpo, Nadine; Bénard, François; Lin, Kuo-Shyan

    2016-09-01

    4-[(18) F]Fluorobenzyltriphenylphosphonium cation ((18) F-FBnTP) is a promising negative membrane potential targeting positron emission tomography tracer. However, the reported multistep radiolabeling approach for the synthesis of (18) F-FBnTP poses a challenge for routine clinical applications. In this study, we demonstrated that (18) F-FBnTP can be prepared in good conversion yields (~60%, nondecay corrected) in just one step via a copper-mediated (18) F-fluorination reaction using a pinacolyl arylboronate precursor. In addition, our data suggest that (18) F-labeled (phosphonium) cations can be efficiently prepared via a copper-mediated (18) F-fluoronation by using triflate as the counterion.

  9. 18F-AV-1451 PET Imaging in Three Patients with Probable Cerebral Amyloid Angiopathy.

    PubMed

    Kim, Hee Jin; Cho, Hanna; Werring, David J; Jang, Young Kyoung; Kim, Yeo Jin; Lee, Jin San; Lee, Juyoun; Jun, Soomin; Park, Seongbeom; Ryu, Young Hoon; Choi, Jae Yong; Cho, Young Seok; Moon, Seung Hwan; Na, Duk L; Lyoo, Chul Hyoung; Seo, Sang Won

    2017-03-06

    Cerebrovascular deposition of amyloid-β, known as cerebral amyloid angiopathy (CAA), is associated with MRI findings of lobar hemorrhage, cerebral microbleeds, and cortical superficial siderosis. Although pathological studies suggest that tau may co-localize with vascular amyloid, this has not yet been investigated in CAA in vivo. Three patients with probable CAA underwent 11C-Pittsburgh Compound B (PiB) PET or 18F-florbetaben PET to evaluate amyloid burden, and 18F-AV-1451 PET to evaluate paired helical filament tau burden. Regions that had cerebral microbleeds or cortical superficial siderosis largely overlapped with those showing increased 18F-AV-1451 and increased 11C-PiB uptake. Our preliminary study raised the possibility that lobar cerebral microbleeds, and cortical superficial siderosis, which are characteristic markers of vascular amyloid, may be associated with local production of paired helical filament tau.

  10. (18)F-Based Pretargeted PET Imaging Based on Bioorthogonal Diels-Alder Click Chemistry.

    PubMed

    Meyer, Jan-Philip; Houghton, Jacob L; Kozlowski, Paul; Abdel-Atti, Dalya; Reiner, Thomas; Pillarsetty, Naga Vara Kishore; Scholz, Wolfgang W; Zeglis, Brian M; Lewis, Jason S

    2016-02-17

    A first-of-its-kind (18)F pretargeted PET imaging approach based on the bioorthogonal inverse electron demand Diels-Alder (IEDDA) reaction between tetrazine (Tz) and trans-cyclooctene (TCO) is presented. As proof-of-principle, a TCO-bearing immunoconjugate of the anti-CA19.9 antibody 5B1 and an Al[(18)F]NOTA-labeled tetrazine radioligand were harnessed for the visualization of CA19.9-expressing BxPC3 pancreatic cancer xenografts. Biodistribution and (18)F-PET imaging data clearly demonstrate that this methodology effectively delineates tumor mass with activity concentrations up to 6.4 %ID/g at 4 h after injection of the radioligand.

  11. No-carrier-added regioselective preparation of 6-( sup 18 F)fluoro-L-dopa

    SciTech Connect

    Lemaire, C.; Guillaume, M.; Cantineau, R.; Christiaens, L. )

    1990-07-01

    This paper describes the preparation of 6-({sup 18}F)fluoro-L-dopa by a no-carrier-added method based on the nucleophilic displacement of nitro groups of two commercially available substrates, 3,4-dimethoxy-2-nitrobenzaldehyde (nitroveratraldehyde) and 6-nitropiperonal. Fluorination was conducted in DMSO with fluorine-18 ({sup 18}F) in the presence of the aminopolyether Kryptofix 222 and potassium carbonate. The condensation of the fluorinated aldehydes with phenyloxazolone and the subsequent hydrolysis with HI/P yield, after purification by HPLC, only the 6-(D, L) isomers. The racemic mixture (50/50) was resolved on an analytical scale chiral column. The method, which requires 100 min (EOB) to complete, produces 6-({sup 18}F)fluoro-L-dopa with a decay-corrected radiochemical yield of 10%, an enantiomeric purity greater than 99%, and a specific activity of 1.2 Ci/mumole.

  12. Automated production of [18F]VAT suitable for clinical PET study of vesicular acetylcholine transporter

    PubMed Central

    Yue, Xuyi; Bognar, Christopher; Zhang, Xiang; Gaehle, Gregory; Moerlein, Stephen M.; Perlmutter, Joel S.; Tu, Zhude

    2015-01-01

    Automated production of a promising radiopharmaceutical (-)-(1-(8-(2-[18F]fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-piperidin-4-yl)(4-fluorophenyl)methanone ([18F]VAT) for vesicular acetylcholine transporter(VAChT) was achieved using a two-step procedure in a current good manufacturing practices fashion. The production of [18F]VAT was accomplished in approximately 140 min, with radiochemical yield of ~15.0% (decay corrected), specific activity > 111 GBq/μmol, radiochemical purity > 99% and mass of VAT ~3.4 μg/batch (n > 10). The radiopharmaceutical product meets all quality control criteria for human use, and is suitable for clinical PET studies of VAChT. PMID:26408913

  13. In situ ceramic fillers of electrospun thermoplastic polyurethane/poly(vinylidene fluoride) based gel polymer electrolytes for Li-ion batteries

    NASA Astrophysics Data System (ADS)

    Wu, Na; Cao, Qi; Wang, Xianyou; Li, Sheng; Li, Xiaoyun; Deng, Huayang

    Gel polymer electrolyte films based on thermoplastic polyurethane (TPU)/poly(vinylidene fluoride) (PVdF) with and without in situ ceramic fillers (SiO 2 and TiO 2) are prepared by electrospinning 9 wt% polymer solution at room temperature. The electrospun TPU-PVdF blending membrane with 3% in situ TiO 2 shows a highest ionic conductivity of 4.8 × 10 -3 S cm -1 with electrochemical stability up to 5.4 V versus Li +/Li at room temperature and has a high tensile strength (8.7 ± 0.3 MPa) and % elongation at break (110.3 ± 0.2). With the superior electrochemical and mechanical performance, it is very suitable for application in polymer lithium ion batteries.

  14. Electro-Spun Poly(vinylidene fluoride) Nanofiber Web as Separator for Lithium Ion Batteries: Effect of Pore Structure and Thickness.

    PubMed

    Lim, Seung-Gyu; Jo, Hye-Dam; Kim, Chan; Kim, Hee-Tak; Chang, Duck-Rye

    2016-01-01

    Electro-spun nanofiber web is highly attractive as a separator for lithium ion batteries because of its high electrical properties. In moving toward wider battery applications of the nanofiber separators, a deeper understanding on the structure and property relationship is highly meaningful. In this regard, we prepared electro-spun poly(vinylidene fluoride) (PVdF) webs with various thicknesses (10.5~100 µm) and investigated their structures and electrochemical performances. As the thickness of the web is decreased, a decrease of porosity and an increase of pore size are resulted in. For the 10.5 µm-thick separator, a minor short-circuit was detected, stressing the importance of reducing pore-size on prevention of short-circuit. However, above the thickness of 21 µm, well-connected, submicron-sized pores are generated, and, with lowering the separator thickness, discharge capacity and rate capability are enhanced owing to the lowered area-specific resistance.

  15. [18F]-fluoro-l-thymidine PET and advanced MRI for preoperative grading of gliomas

    PubMed Central

    Collet, S.; Valable, S.; Constans, J.M.; Lechapt-Zalcman, E.; Roussel, S.; Delcroix, N.; Abbas, A.; Ibazizene, M.; Bernaudin, M.; Barré, L.; Derlon, J.M.; Guillamo, J.S.

    2015-01-01

    Purpose Conventional MRI based on contrast enhancement is often not sufficient in differentiating grade II from grade III and grade III from grade IV diffuse gliomas. We assessed advanced MRI, MR spectroscopy and [18F]-fluoro-l-thymidine ([18F]-FLT) PET as tools to overcome these limitations. Methods In this prospective study, thirty-nine patients with diffuse gliomas of grades II, III or IV underwent conventional MRI, perfusion, diffusion, proton MR spectroscopy (1H-MRS) and [18F]-FLT-PET imaging before surgery. Relative cerebral blood volume (rCBV), apparent diffusion coefficient (ADC), Cho/Cr, NAA/Cr, Cho/NAA and FLT-SUV were compared between grades. Results Cho/Cr showed significant differences between grade II and grade III gliomas (p = 0.03). To discriminate grade II from grade IV and grade III from grade IV gliomas, the most relevant parameter was the maximum value of [18F]-FLT uptake FLTmax (respectively, p < 0.001 and p < 0.0001). The parameter showing the best correlation with the grade was the mean value of [18F]-FLT uptake FLTmean (R2 = 0.36, p < 0.0001) and FLTmax (R2 = 0.5, p < 0.0001). Conclusion Whereas advanced MRI parameters give indications for the grading of gliomas, the addition of [18F]-FLT-PET could be of interest for the accurate preoperative classification of diffuse gliomas, particularly for identification of doubtful grade III and IV gliomas. PMID:26106569

  16. 18F-FDG PET in the Evaluation of Acuity of Deep Vein Thrombosis

    PubMed Central

    Rondina, Matthew T.; Lam, Uyen T.; Pendleton, Robert C.; Kraiss, Larry W.; Wanner, Nathan; Zimmerman, Guy A.; Hoffman, John M.; Hanrahan, Christopher; Boucher, Kenneth; Christian, Paul E.; Butterfield, Regan I.; Morton, Kathryn A.

    2013-01-01

    Purpose 18F-FDG PET has been used for vascular disease, but its role in deep vein thrombosis (DVT) remains prospectively unexplored. Patients and Methods Whole-body 18F-FDG PET/CT scans were performed in patients 1 to 10 weeks after onset of symptomatic DVT (n = 12) and in control subjects without DVT (n = 24). The metabolic activity (SUVmax) of thrombosed and contralateral nonthrombosed vein segments was determined. The sensitivity and specificity of 18F-FDG PET/CT for the diagnosis of DVT were determined by receiver operating characteristic curve analyses. In 2 patients with DVT, changes in the metabolic activity of thrombosed vein segments in serial 18F-FDG PET scans. Results The metabolic activity in thrombosed veins [SUVmax, 2.41 (0.75)] was visually appreciable and significantly higher than in nonthrombosed veins in either the contralateral extremity of patients with DVT [SUVmax, 1.09 (0.25), P = 0.007] or control subjects [1.21 (0.22), P < 001]. The area under the receiver operating characteristic curve for SUVmax was 0.9773 (P < 001), indicating excellent accuracy. An SUVmax threshold of greater than 1.645 was 87.5% sensitive and 100% specific for DVT. Metabolic activity in thrombosed veins correlated significantly with time from DVT symptom onset (decrease in SUVmax of 0.02/d, P < 0.05). Best-fit-line analyses suggested that approximately 84 to 91 days after acute DVT, the maximum metabolic activity of thrombosed veins would return to normal levels. Conclusions 18F-FDG PET/CT is accurate for detecting acute symptomatic, proximal DVT. Metabolic activity in thrombosed veins decreases with time, suggesting that 18F-FDG PET may be helpful in assessing the age of the clot. PMID:23154470

  17. Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies

    PubMed Central

    Mittra, Erik S.; Koglin, Norman; Mosci, Camila; Kumar, Meena; Hoehne, Aileen; Keu, Khun Visith; Iagaru, Andrei H.; Mueller, Andre; Berndt, Mathias; Bullich, Santiago; Friebe, Matthias; Schmitt-Willich, Heribert; Gekeler, Volker; Fels, Lüder M.; Bacher-Stier, Claudia; Moon, Dae Hyuk; Chin, Frederick T.; Stephens, Andrew W.; Dinkelborg, Ludger M.; Gambhir, Sanjiv S.

    2016-01-01

    Purpose (S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid (18F-FSPG) is a novel radiopharmaceutical for Positron Emission Tomography (PET) imaging. It is a glutamate analogue that can be used to measure xC- transporter activity. This study was performed to assess the feasibility of 18F-FSPG for imaging orthotopic brain tumors in small animals and the translation of this approach in human subjects with intracranial malignancies. Experimental Design For the small animal study, GS9L glioblastoma cells were implanted into brains of Fischer rats and studied with 18F-FSPG, the 18F-labeled glucose derivative 18F-FDG and with the 18F-labeled amino acid derivative 18F-FET. For the human study, five subjects with either primary or metastatic brain cancer were recruited (mean age 50.4 years). After injection of 300 MBq of 18F-FSPG, 3 whole-body PET/Computed Tomography (CT) scans were obtained and safety parameters were measured. The three subjects with brain metastases also had an 18F-FDG PET/CT scan. Quantitative and qualitative comparison of the scans was performed to assess kinetics, biodistribution, and relative efficacy of the tracers. Results In the small animals, the orthotopic brain tumors were visualized well with 18F-FSPG. The high tumor uptake of 18F-FSPG in the GS9L model and the absence of background signal led to good tumor visualization with high contrast (tumor/brain ratio: 32.7). 18F-FDG and 18F-FET showed T/B ratios of 1.7 and 2.8, respectively. In the human pilot study, 18F-FSPG was well tolerated and there was similar distribution in all patients. All malignant lesions were positive with 18F-FSPG except for one low-grade primary brain tumor. In the 18F-FSPG-PET-positive tumors a similar T/B ratio was observed as in the animal model. Conclusions 18F-FSPG is a novel PET radiopharmaceutical that demonstrates good uptake in both small animal and human studies of intracranial malignancies. Future studies on larger numbers of subjects and a wider array of brain tumors

  18. Enhanced Aqueous Suzuki–Miyaura Coupling Allows Site-Specific Polypeptide 18F-Labeling

    PubMed Central

    2013-01-01

    The excesses of reagents used in protein chemistry are often incompatible with the reduced or even inverse stoichiometries used for efficient radiolabeling. Analysis and screening of aqueous Pd(0) ligand systems has revealed the importance of a guanidine core and the discovery of 1,1-dimethylguanidine as an enhanced ligand for aqueous Suzuki–Miyaura cross-coupling. This novel Pd catalyst system has now allowed the labeling of small molecules, peptides, and proteins with the fluorine-18 prosthetic [18F]4-fluorophenylboronic acid. These findings now enable site-specific protein 18F-labeling under biologically compatible conditions using a metal-triggered reaction. PMID:23991754

  19. [18F]FDG Accumulation in Early Coronary Atherosclerotic Lesions in Pigs

    PubMed Central

    Tarkia, Miikka; Saraste, Antti; Stark, Christoffer; Vähäsilta, Tommi; Savunen, Timo; Strandberg, Marjatta; Saunavaara, Virva; Tolvanen, Tuula; Teuho, Jarmo; Teräs, Mika; Metsälä, Olli; Rinne, Petteri; Heinonen, Ilkka; Savisto, Nina; Pietilä, Mikko; Saukko, Pekka; Roivainen, Anne; Knuuti, Juhani

    2015-01-01

    Objective Inflammation is an important contributor to atherosclerosis progression. A glucose analogue 18F-fluorodeoxyglucose ([18F]FDG) has been used to detect atherosclerotic inflammation. However, it is not known to what extent [18F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [18F]FDG to various stages of coronary plaques in a pig model. Methods First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days) in farm pigs (n = 10). After 6 months on high-fat diet, pigs underwent dual-gated cardiac PET/CT to measure [18F]FDG uptake in coronary arteries. Coronary segments (n = 33) were harvested for ex vivo measurement of radioactivity and autoradiography (ARG). Results Intimal thickening was observed in 16 segments and atheroma type plaques in 10 segments. Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher [18F]FDG accumulation in the intimal thickening and 4.1±2.3 times higher in the atheromas (P = 0.004 and P = 0.003, respectively). Ex vivo mean vessel-to-blood ratio was higher in segments with atheroma than those without atherosclerosis (2.6±1.2 vs. 1.3±0.7, P = 0.04). In vivo PET imaging showed the highest target-to-background ratio (TBR) of 2.7. However, maximum TBR was not significantly different in segments without atherosclerosis (1.1±0.5) and either intimal thickening (1.2±0.4, P = 1.0) or atheroma (1.6±0.6, P = 0.4). Conclusions We found increased uptake of [18F]FDG in coronary atherosclerotic lesions in a pig model. However, uptake in these early stage lesions was not detectable with in vivo PET imaging. Further studies are needed to clarify whether visible [18F]FDG uptake in coronary arteries represents more advanced, highly inflamed plaques. PMID:26120829

  20. 18F-FDG PET/CT in the diagnosis of prosthetic valve endocarditis.

    PubMed

    Fagman, Erika; van Essen, Martijn; Fredén Lindqvist, Johan; Snygg-Martin, Ulrika; Bech-Hanssen, Odd; Svensson, Gunnar

    2016-04-01

    Recent studies have shown promising results using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the diagnosis of prosthetic valve endocarditis (PVE). However, previous studies did not include negative controls. The aim of this study was to compare (18)F-FDG-uptake around prosthetic aortic valves in patients with and without PVE and to determine the diagnostic performance of (18)F-FDG PET/CT in the diagnosis of PVE. (18)F-FDG PET/CT examinations in patients with a prosthetic aortic valve performed 2008-2014 were retrieved. Eight patients with a final diagnosis of definite PVE were included in the analysis of the diagnostic performance of (18)F-FDG PET/CT. Examinations performed on suspicion of malignancy in patients without PVE (n = 19) were used as negative controls. Visual and semi-quantitative analysis was performed. Maximal standardized uptake value (SUVmax) in the valve area was measured and SUVratio was calculated by dividing valve SUVmax by SUVmax in the descending aorta. The sensitivity was 75 %, specificity 84 %, positive likelihood ratio [LR(+)] 4.8 and negative likelihood ratio [LR(-)] 0.3 on visual analysis. Both SUVmax and SUVratio were significantly higher in PVE patients [5.8 (IQR 3.5-6.5) and 2.4 (IQR 1.7-3.0)] compared to non-PVE patients [3.2 (IQR 2.8-3.8) and 1.5 (IQR 1.3-1.6)] (p < 0.001). ROC-curve analysis of SUVratio yielded an area under the curve of 0.90 (95 % CI 0.74-1.0). (18)F-FDG-uptake around non-infected aortic prosthetic valves was low. The level of (18)F-FDG-uptake in the prosthetic valve area showed a good diagnostic performance in the diagnosis of PVE.

  1. Routine synthesis of L-(18F)6-fluorodopa with fluorine-18 acetyl hypofluorite

    SciTech Connect

    Adam, M.J.; Ruth, T.J.; Grierson, J.R.; Abeysekera, B.; Pate, B.D.

    1986-09-01

    The synthesis of L-(/sup 18/F)6-fluorodopa (2.4-10.6 mCi) was done by passing gaseous (/sup 18/F)acetyl hypofluorite through a solution of L-methyl-N- acetyl-(beta-(3-methoxy-4-acetoxyphenyl))alaninate in acetic acid at room temperature followed by the hydrolysis of the intermediate products with concentrated hydriodic acid. The desired fluorodopa isomer was isolated in 8% EOB radiochemical yield by high performance liquid chromatography in an overall synthesis time of 100 min.

  2. New Chelators for Low Temperature Al(18)F-Labeling of Biomolecules.

    PubMed

    Cleeren, Frederik; Lecina, Joan; Billaud, Emilie M F; Ahamed, Muneer; Verbruggen, Alfons; Bormans, Guy M

    2016-03-16

    The Al(18)F labeling method is a relatively new approach that allows radiofluorination of biomolecules such as peptides and proteins in a one-step procedure and in aqueous solution. However, the chelation of the {Al(18)F}(2+) core with the macrocyclic chelators NOTA or NODA requires heating to 100-120 °C. Therefore, we have developed new polydentate ligands for the complexation of {Al(18)F}(2+) with good radiochemical yields at a temperature of 40 °C. The stability of the new Al(18)F-complexes was tested in phosphate buffered saline (PBS) at pH 7.4 and in rat serum. The stability of the Al(18)F-L3 complex was found to be comparable to that of the previously reported Al(18)F-NODA complex up to 60 min in rat serum. Moreover, the biodistribution of Al(18)F-L3 in healthy mice showed the absence of in vivo defluorination since no significant bone uptake was observed, whereas the major fraction of activity at 60 min p.i. was observed in liver and intestines, indicating hepatobiliary clearance of the radiolabeled ligand. The acyclic chelator H3L3 proved to be a good lead candidate for labeling of heat-sensitive biomolecules with fluorine-18. In order to obtain a better understanding of the different factors influencing the formation and stability of the complex, we carried out more in-depth experiments with ligand H3L3. As a proof of concept, we successfully conjugated the new AlF-chelator with the urea-based PSMA inhibitor Glu-NH-CO-NH-Lys to form Glu-NH-CO-NH-Lys(Ahx)L3, and a biodistribution study in healthy mice was performed with the Al(18)F-labeled construct. This new class of AlF-chelators may have a great impact on PET radiochemical space as it will stimulate the rapid development of new fluorine-18 labeled peptides and other heat-sensitive biomolecules.

  3. Early detection of encephalitis with (18)F-FDG PET/CT.

    PubMed

    Gaeta, M C; Godani, M; Nunziata, R; Capellini, C; Ciarmiello, A

    2015-01-01

    Encephalitis is a relatively rare condition for which making an accurate diagnosis can be challenging. In fact, clinical features are not specific and structural imaging can be normal in a considerable number of cases. However, an early diagnosis is important as many forms of treatment are effective if started promptly. Even though recent guidelines do not recommend (18)F-FDG PET/CT for patients with suspected encephalitis, the case presented suggests that (18)F-FDG PET/CT may play a relevant role for the early diagnosis of this clinical condition.

  4. (18)F-FDG PET/CT in bilateral primary adrenal T-cell lymphoma.

    PubMed

    Santhosh, Sampath; Mittal, Bhagwant Rai; Shankar, Praveen; Kashyap, Raghava; Bhattacharya, Anish; Singh, Baljinder; Das, Ashim; Bhansali, Anil

    2011-01-01

    Primary adrenal lymphoma is extremely rare. We report a young patient who presented with non- specific symptoms of fever and abdominal pain. Conventional imaging modalities demonstrated bilateral bulky adrenal masses, and whole-body fluorine-18-fluorodesoxyglucose ((18)F-FDG) positron emission tomography/computed tomography showed intense (18)F-FDG-avid bilateral adrenal masses with no evidence of extra-adrenal spread. A pathological diagnosis of non-Hodgkin lymphoma of peripheral T-cell type was made. The present case indicates that primary adrenal lymphoma should be included in the differential diagnosis of bilateral adrenal masses.

  5. Effect of pH, fluoride and hydrofluoric acid concentration on ion release from NiTi wires with various coatings.

    PubMed

    Katic, Visnja; Curkovic, Lidija; Bosnjak, Magdalena Ujevic; Peros, Kristina; Mandic, Davor; Spalj, Stjepan

    2017-03-31

    Aim was to determine effect of pH, fluoride (F(-)) and hydrofluoric acid concentration (HF) on dynamic of nickel (Ni(2+)) and titanium (Ti(4+)) ions release. Nickel-titanium wires with untreated surface (NiTi), rhodium (RhNiTi) and nitride (NNiTi) coating were immersed once a week for five min in remineralizing agents, followed by immersion to artificial saliva. Ion release was recorded after 3, 7, 14, 21 and 28 days. Pearson correlations and linear regression were used for statistical analysis. Release of Ni(2+) from NiTi and NNiTi wires correlated highly linearly positively with HF (r=0.948 and 0.940, respectively); for RhNiTi the correlation was lower and negative (r=-0.605; p<0.05). The prediction of Ti(4+) release was significant for NiTi (r=0.797) and NNiTi (r=0.788; p<0.05) wire. Association with F(-) was lower; for pH it was not significant. HF predicts the release of ions from the NiTi wires better than the pH and F(-) of the prophylactic agents.

  6. Anion Binding Properties of Alkynylplatinum(II) Complexes with Amide-Functionalized Terpyridine: Host–Guest Interactions and Fluoride Ion-Induced Deprotonation**

    PubMed Central

    Yeung, Margaret Ching-Lam; Chu, Ben Wai-Kin; Yam, Vivian Wing-Wah

    2014-01-01

    Molecular sensors able to detect ions are of interest due to their potential application in areas such as pollutant sequestration. Alkynylplatinum(II) terpyridine complexes with an amide-based receptor moiety have been synthesized and characterized. Their anion binding properties based on host–guest interactions have been examined with the use of UV-vis absorption and emission spectral titration studies. Spectral changes were observed for both complexes upon the addition of spherical and nonspherical anions. Their titration profiles were shown to be in good agreement with theoretical results predicting a 1:1 binding model, and the binding constants were determined from the experimental data. Drastic color changes from yellow to orange–red were observed for one of the complexes upon titration with fluoride (F−) ion in acetone. These changes were ascribed to the deprotonation of the amide functionalities induced by F− ion, and this was confirmed by the restoration of spectral changes upon addition of trifluoroacetic acid to the F− ion–complex mixture as well as by electrospray ionization mass spectrometry (ESI-MS) data. PMID:25478312

  7. The effect of core and lanthanide ion dopants in sodium fluoride-based nanocrystals on phagocytic activity of human blood leukocytes

    NASA Astrophysics Data System (ADS)

    Sojka, Bartlomiej; Liskova, Aurelia; Kuricova, Miroslava; Banski, Mateusz; Misiewicz, Jan; Dusinska, Maria; Horvathova, Mira; Ilavska, Silvia; Szabova, Michaela; Rollerova, Eva; Podhorodecki, Artur; Tulinska, Jana

    2017-02-01

    Sodium fluoride-based β-NaLnF4 nanoparticles (NPs) doped with lanthanide ions are promising materials for application as luminescent markers in bio-imaging. In this work, the effect of NPs doped with yttrium (Y), gadolinium (Gd), europium (Eu), thulium (Tm), ytterbium (Yb) and terbium (Tb) ions on phagocytic activity of monocytes and granulocytes and the respiratory burst was examined. The surface functionalization of <10-nm NPs was performed according to our variation of patent pending ligand exchange method that resulted in meso-2,3-dimercaptosuccinic acid (DMSA) molecules on their surface. Y-core-based NCs were doped with Eu ions, which enabled them to be excited with UV light wavelengths. Cultures of human peripheral blood ( n = 8) were in vitro treated with five different concentrations of eight NPs for 24 h. In summary, neither type of nanoparticles is found toxic with respect to conducted test; however, some cause toxic effects (they have statistically significant deviations compared to reference) in some selected doses tested. Both core types of NPs (Y-core and Gd-core) impaired the phagocytic activity of monocytes the strongest, having minimal or none whatsoever influence on granulocytes and respiratory burst of phagocytic cells. The lowest toxicity was observed in Gd-core, Yb, Tm dopants and near-infrared nanoparticles. Clear dose-dependent effect of NPs on phagocytic activity of leukocytes and respiratory burst of cells was observed for limited number of samples.

  8. Effects of fluoride and other halogen ions on the external stress corrosion cracking of Type 304 austenitic stainless steel

    SciTech Connect

    Whorlow, K.M.; Hutto, F.B. Jr.

    1997-07-01

    The drip procedure from the Standard Test Method for Evaluating the Influence of Thermal Insulation on External Stress Corrosion Cracking Tendency of Austenitic Stainless Steel (ASTM C 692-95a) was used to research the effect of halogens and inhibitors on the External Stress Corrosion Cracking (ESCC) of Type 304 stainless steel as it applies to Nuclear Regulatory Commission Regulatory Guide 1.36, Nonmetallic Thermal Insulation for Austenitic Stainless Steel. The solutions used in this research were prepared using pure chemical reagents to simulate the halogens and inhibitors found in insulation extraction solutions. The results indicated that sodium silicate compounds that were higher in sodium were more effective for preventing chloride-induced ESCC in Type 304 austenitic stainless steel. Potassium silicate (all-silicate inhibitor) was not as effective as sodium silicate. Limited testing with sodium hydroxide (all-sodium inhibitor) indicated that it may be effective as an inhibitor. Fluoride, bromide, and iodide caused minimal ESCC which could be effectively inhibited by sodium silicate. The addition of fluoride to the chloride/sodium silicate systems at the threshold of ESCC appeared to have no synergistic effect on ESCC. The mass ratio of sodium + silicate (mg/kg) to chloride (mg/kg) at the lower end of the NRC RG 1.36 Acceptability Curve was not sufficient to prevent ESCC using the methods of this research.

  9. Comparison of Positron Emission Tomography Using 2-[18F]-fluoro-2-deoxy-D-glucose and 3-deoxy-3-[18F]-fluorothymidine in Lung Cancer Imaging

    PubMed Central

    Wang, Fu-Li; Tan, Ye-Ying; Gu, Xiang-Min; Li, Tian-Ran; Lu, Guang-Ming; Liu, Gang; Huo, Tian-Long

    2016-01-01

    Background: The detection of solitary pulmonary nodules (SPNs) that may potentially develop into a malignant lesion is essential for early clinical interventions. However, grading classification based on computed tomography (CT) imaging results remains a significant challenge. The 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/CT imaging produces both false-positive and false-negative findings for the diagnosis of SPNs. In this study, we compared 18F-FDG and 3-deoxy-3-[18F]-fluorothymidine (18F-FLT) in lung cancer PET/CT imaging. Methods: The binding ratios of the two tracers to A549 lung cancer cells were calculated. The mouse lung cancer model was established (n = 12), and micro-PET/CT analysis using the two tracers was performed. Images using the two tracers were collected from 55 lung cancer patients with SPNs. The correlation among the cell-tracer binding ratios, standardized uptake values (SUVs), and Ki-67 proliferation marker expression were investigated. Results: The cell-tracer binding ratio for the A549 cells using the 18F-FDG was greater than the ratio using 18F-FLT (P < 0.05). The Ki-67 expression showed a significant positive correlation with the 18F-FLT binding ratio (r = 0.824, P < 0.01). The tumor-to-nontumor uptake ratio of 18F-FDG imaging in xenografts was higher than that of 18F-FLT imaging. The diagnostic sensitivity, specificity, and the accuracy of 18F-FDG for lung cancer were 89%, 67%, and 73%, respectively. Moreover, the diagnostic sensitivity, specificity, and the accuracy of 18F-FLT for lung cancer were 71%, 79%, and 76%, respectively. There was an obvious positive correlation between the lung cancer Ki-67 expression and the mean maximum SUV of 18F-FDG and 18F-FLT (r = 0.658, P < 0.05 and r = 0.724, P < 0.01, respectively). Conclusions: The 18F-FDG uptake ratio is higher than that of 18F-FLT in A549 cells at the cellular level. 18F-FLT imaging might be superior for the quantitative diagnosis of lung tumor

  10. Synthesis and biological evaluation of anti-1-amino-2-[18F]fluoro-cyclobutyl-1-carboxylic acid (anti-2-[18F]FACBC) in rat 9L gliosarcoma.

    PubMed

    Yu, Weiping; Williams, Larry; Camp, Vernon M; Olson, Jeffrey J; Goodman, Mark M

    2010-04-01

    A new [(18)F] labeled amino acid anti-1-amino-2-[(18)F]fluoro-cyclobutyl-1-carboxylic acid 9 (anti-2-[(18)F]FACBC) was synthesized in 30% decay-corrected yield with high radiochemical purity over 99%. The cyclic sulfamidate precursor was very stable and highly reactive towards nucleophilic radiofluorination. Cell uptake assays with rat 9L gliosarcoma cells showed that [(18)F]9 was transported into tumor cells via multiple amino acid transport systems, including L and A systems. Biodistribution study in rats with intracranial 9L gliosarcoma tumors demonstrated that [(18)F]9 had a rapid and prolonged accumulation in tumors with 26:1 tumor to brain ratio at 120 min post-injection. In this model, [(18)F]9 is a potential PET tracer for brain tumor imaging.

  11. Design of CGMP Production of 18F- and 68Ga-Radiopharmaceuticals

    PubMed Central

    Chu, Pei-Chun; Chao, Hao-Yu; Shieh, Wei-Chen; Chen, Chuck C.

    2014-01-01

    Objective. Radiopharmaceutical production process must adhere to current good manufacturing process (CGMP) compliance to ensure the quality of precursor, prodrug (active pharmaceutical ingredient, API), and the final drug product that meet acceptance criteria. We aimed to develop an automated system for production of CGMP grade of PET radiopharmaceuticals. Methods. The hardware and software of the automated synthesizer that fit in the hot cell under cGMP requirement were developed. Examples of production yield and purity for 68Ga-DOTATATE and 18F-FDG at CGMP facility were optimized. Analytical assays and acceptance criteria for cGMP grade of 68Ga-DOTATATE and 18F-FDG were established. Results. CGMP facility for the production of PET radiopharmaceuticals has been established. Radio-TLC and HPLC analyses of 68Ga-DOTATATE and 18F-FDG showed that the radiochemical purity was 92% and 96%, respectively. The products were sterile and pyrogenic-free. Conclusion. CGMP compliance of radiopharmaceuticals has been reviewed. 68Ga-DOTATATE and 18F-FDG were synthesized with high radiochemical yield under CGMP process. PMID:25276810

  12. Granulocytic sarcoma of the pancreas on 18F-FDG PET/CT

    PubMed Central

    Ishii, Akira; Kondo, Tadakazu; Oka, Tomomi; Nakamoto, Yuji; Takaori-Kondo, Akifumi

    2016-01-01

    Abstract Rationale: Granulocytic sarcoma (GS) is defined as leukemia infiltration in any organ other than the bone marrow. GS rarely occurs in the pancreas. Here, we present the first report of GS in the pancreas on 18F-fluorodexyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Patient concerns: A 19-year-old male patient with acute myeloid leukemia received a human leukocyte antigen-haploidentical stem cell transplant as a second transplant while in second complete remission. Interventions: After a second stem cell transplant, obstructive pancreatitis accompanied by a mass in the pancreatic head was observed. FDG-PET/CT revealed abnormal activity in the head of the pancreas and the skin in the patient's left breast area. Diagnoses: Pathological examination demonstrated relapsed acute myeloid leukemia in both the lesions. Outcomes: This is the first report showing the 18F-FDG PET/CT findings of GS in the pancreas. Lessons: 18F-FDG PET/CT may help determine the stage of GS. PMID:27930567

  13. Intracranial Leptomeningeal Carcinomatosis from Breast Cancer Detected on 18F-FDG PET.

    PubMed

    Carra, Bradley J; Clemenshaw, Michael N

    2015-09-01

    Leptomeningeal carcinomatosis is an uncommon manifestation of non-central nervous system (CNS) metastatic disease. Diagnosis, however, has important prognostic and treatment implications. We present a case in which intracranial leptomeningeal carcinomatosis from a primary breast cancer was detected with (18)F-FDG PET/CT, despite its low sensitivity for detection of CNS metastases from non-CNS primary tumors.

  14. ADMP Mixing of Tank 18F: History, Modeling, Testing, and Results

    SciTech Connect

    LEISHEAR, ROBERTA

    2004-03-29

    Residual radioactive waste was removed from Tank 18F in the F-Area Tank Farm at Savannah River Site (SRS), using the advanced design mixer pump (ADMP). Known as a slurry pump, the ADMP is a 55 foot long pump with an upper motor mounted to a steel super structure, which spans the top of the waste tank. The motor is connected by a long vertical drive shaft to a centrifugal pump, which is submerged in waste near the tank bottom. The pump mixes, or slurries, the waste within the tank so that it may be transferred out of the tank. Tank 18F is a 1.3 million gallon, 85 foot diameter underground waste storage tank, which has no internal components such as cooling coils or structural supports. The tank contained a residual 47,000 gallons of nuclear waste, consisting of a gelatinous radioactive waste known as sludge and particulate zeolite. The prediction of the ADMP success was based on nearly twenty five years of research and the application of that research to slurry pump technology. Many personnel at SRS and Pacific Northwest National Laboratories (PNNL) have significantly contributed to these efforts. This report summarizes that research which is pertinent to the ADMP performance in Tank 18F. In particular, a computational fluid dynamics (CFD) model was applied to predict the performance of the ADMP in Tank 18F.

  15. Brain tumor imaging with synthesized /sup 18/F-fluorophenylalanine and positron emission tomography

    SciTech Connect

    Mineura, K.; Kowada, M.; Shishido, F.

    1989-06-01

    Two patients with cerebral gliomas were studied with 18F-fluorophenylalanine, newly synthesized by the electrophilic substitution reaction, using positron emission tomography. The tracer accumulated markedly in the tumor lesion and delineated the extent of the lesion. This new tracer will be promising in the diagnosis of gliomas.

  16. N-( sup 18 F)fluoroacetyl-D-glucosamine: A potential agent for cancer diagnosis

    SciTech Connect

    Fujiwara, T.; Kubota, K.; Sato, T.; Matsuzawa, T.; Tada, M.; Iwata, R.; Itoh, M.; Hatazawa, J.; Sato, K.; Fukuda, H. )

    1990-10-01

    Positron labeled substrates such as sugars, amino acids, and nucleosides have been investigated for the in-vivo evaluation of biochemical processes in cancerous tissue. Hexosamines are obligatory structural components of many biologically important macromolecules, including membrane glycoproteins and mucopolysaccharide. We evaluated a new synthesized pharmaceutical, N-({sup 18}F)fluoroacetyl-D-glucosamine ({sup 18}F-FAG), which is a structural analog of N-acetyl-D-glucosamine. C3H/HeMsNRS mice bearing spontaneous hepatomas were used for the tissue distribution study. At 60 min after injection, high uptakes were found in tumor (5.16, mean value of %dose/g), liver (3.71), and kidney (3.27). The tumor uptake of 18F-FAG showed the highest value in all tissue. In the PET study, VX-2 carcinoma of the rabbit was clearly visualized. Our preliminary results suggest that {sup 18}F-FAG has potential as a new agent for tumor imaging.

  17. Evaluation of Arginine Deiminase Treatment in Melanoma Xenografts Using 18F-FLT PET

    PubMed Central

    Stelter, Lars; Fuchs, Simon; Jungbluth, Achim A.; Ritter, Gerd; Longo, Valerie A.; Zanzonico, Pat; Raschzok, Nathanael; Sauer, Igor M.; Bomalaski, John S.; Larson, Steven M.

    2015-01-01

    Purpose This study aims to develop a molecular imaging strategy for response assessment of arginine deiminase (ADI) treatment in melanoma xenografts using 3′-[18F]fluoro-3′-deoxythymidine ([18F]-FLT) positron emission tomography (PET). Procedures F-FLT response to ADI therapy was studied in preclinical models of melanoma in vitro and in vivo. The molecular mechanism of response to ADI therapy was investigated, with a particular emphasis on biological pathways known to regulate 18F-FLT metabolism. Results Proliferation of SK-MEL-28 melanoma tumors was potently inhibited by ADI treatment. However, no metabolic response was observed in FLT PET, presumably based on the known ADI-induced degradation of PTEN, followed by instability of the tumor suppressor p53 and a relative overexpression of thymidine kinase 1, the enzyme mainly responsible for intracellular FLT processing. Conclusion The specific pharmacological properties of ADI preclude using 18F-FLT to evaluate clinical response in melanoma and argue for further studies to explore the use of other clinically applicable PET tracers in ADI treatment. PMID:23722880

  18. Plasmacytoma of the ovary: additional role of 18F-FDG PET/CT.

    PubMed

    Santhosh, Sampath; Mittal, Bhagwant Rai; Raveendran, Ainharan; Jain, Vanita; Nijhawan, Raje; Kumar, Ritesh; Bhattacharya, Anish; Sharma, Suresh C

    2013-05-01

    We report a case of ovarian plasmacytomas where 18F-FDG PET/CT helped in staging by demonstrating increased FDG uptake limited to the ovary, and hence, surgical treatment was carried out as the disease was localized to the ovary.

  19. Synthetic Minor NSR Permit: XTO Energy, Inc. - RBU 11-18F Compressor Station

    EPA Pesticide Factsheets

    This page contains the response to public comments, the final synthetic minor NSR permit, and the administrative record for the XTO Energy, Inc. RBU 11-18F Compressor Station, located on the Uintah and Ouray Indian Reservation in Uintah County, UT.

  20. (18)F-FLT and (18)F-FDG PET-CT imaging in the evaluation of early therapeutic effects of chemotherapy on Walker 256 tumor-bearing rats.

    PubMed

    Xu, Weina; Yu, Shupeng; Xin, Jun; Guo, Qiyong

    2016-12-01

    The present study aimed to evaluate the early therapeutic effects of chemotherapy on Walker 256 tumor-bearing Wistar rats via F-18-fluoro-3'-deoxy-3'-L-fluorothymidine ((18)F-FLT) and F-18-fluoro-deoxyglucose ((18)F-FDG) positron emission tomography-computed tomography (PET-CT) imaging. Walker 256 tumor-bearing Wistar rats were subjected to (18)F-FLT and (18)F-FDG PET-CT imaging prior to and 24 and 48 h after epirubicin chemotherapy. (18)F-FLT and (18)F-FDG uptake [tumor/muscle (T/M)], the percentage of injected dose per gram (% ID/g), and the Ki-67 labeling index (LI-Ki-67) were quantitatively determined for each rat prior to and following epirubicin chemotherapy. The correlation between % ID/g and tumor LI-Ki-67 was analyzed. Both (18)F-FLT and (18)F-FDG tumor uptake decreased significantly at 24 and 48 h after chemotherapy (P<0.01 and P<0.05, respectively). LI-Ki-67 also significantly reduced 24 and 48 h after chemotherapy (P<0.001). Furthermore, (18)F-FLT and (18)F-FDG T/M tumor uptake correlated positively with LI-Ki-67 before and after chemotherapy (r=0.842 and 0.813, respectively). During the early post-chemotherapy stage, (18)F-FLT and (18)F-FDG uptake in Walker 256 tumors reduced significantly, which correlated positively with the tumor cell proliferative activity.

  1. 18F-FLT and 18F-FDG PET-CT imaging in the evaluation of early therapeutic effects of chemotherapy on Walker 256 tumor-bearing rats

    PubMed Central

    Xu, Weina; Yu, Shupeng; Xin, Jun; Guo, Qiyong

    2016-01-01

    The present study aimed to evaluate the early therapeutic effects of chemotherapy on Walker 256 tumor-bearing Wistar rats via F-18-fluoro-3′-deoxy-3′-L-fluorothymidine (18F-FLT) and F-18-fluoro-deoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) imaging. Walker 256 tumor-bearing Wistar rats were subjected to 18F-FLT and 18F-FDG PET-CT imaging prior to and 24 and 48 h after epirubicin chemotherapy. 18F-FLT and 18F-FDG uptake [tumor/muscle (T/M)], the percentage of injected dose per gram (% ID/g), and the Ki-67 labeling index (LI-Ki-67) were quantitatively determined for each rat prior to and following epirubicin chemotherapy. The correlation between % ID/g and tumor LI-Ki-67 was analyzed. Both 18F-FLT and 18F-FDG tumor uptake decreased significantly at 24 and 48 h after chemotherapy (P<0.01 and P<0.05, respectively). LI-Ki-67 also significantly reduced 24 and 48 h after chemotherapy (P<0.001). Furthermore, 18F-FLT and 18F-FDG T/M tumor uptake correlated positively with LI-Ki-67 before and after chemotherapy (r=0.842 and 0.813, respectively). During the early post-chemotherapy stage, 18F-FLT and 18F-FDG uptake in Walker 256 tumors reduced significantly, which correlated positively with the tumor cell proliferative activity. PMID:28101193

  2. Molecular imaging of therapy response with 18F-FLT and 18F-FDG following cyclophosphamide and mTOR inhibition

    PubMed Central

    Saint-Hubert, Marijke De; Brepoels, Lieselot; Devos, Ellen; Vermaelen, Peter; Groot, Tjibe De; Tousseyn, Thomas; Mortelmans, Luc; Mottaghy, Felix M

    2012-01-01

    Purpose Evaluation and comparison of 3’-[18F]-fluoro-3’-deoxy-L-thymidine (FLT) and 2-[18F]-fluoro-2-deoxyglucose (FDG)-PET to monitor early response following both cyclophosphamide and temsirolimus treatment in a mouse model of Burkitt lymphoma. Methods Daudi xenograft mice were treated with either cyclophosphamide or temsirolimus and imaged with FLT-PET and FDG-PET on appropriate days post therapy inititiation. Immunohistochemical (IHC) studies (H&E, TUNEL, CD20, PCNA and ki-67) and DNA flow cytometry studies were performed. Results FDG tumor uptake decreased immediately after cyclophosphamide treatment while FLT-PET showed only a late and less pronounced decrease. A fast induction of apoptosis was observed together with an early accumulation of cells in the S-phase of the cell cycle, suggesting DNA repair. Temsirolimus treatment reduced both FDG and FLT tumor uptake immediately after therapy and resulted in a fast induction of apoptosis and G0-G1 phase accumulation. Conclusion FLT response was less distinct than FDG response and may be controlled by DNA repair early after cyclophosphamide. Nevertheless, FLT-PET was able to reflect decreased proliferation following temsirolimus. PMID:23133806

  3. Positron emission tomography in ovarian cancer: 18F-deoxy-glucose and 16α-18F-fluoro-17β-estradiol PET

    PubMed Central

    Yoshida, Yoshio; Kurokawa, Tetsuji; Tsujikawa, Tetuya; Okazawa, Hidehiko; Kotsuji, Fumikazu

    2009-01-01

    The most frequently used molecular imaging technique is currently 18F-deoxy-glucose (FDG) positron emission tomography (PET). FDG-PET holds promise in the evaluation of recurrent or residual ovarian cancer when CA125 levels are rising and conventional imaging, such as ultrasound, CT, or MRI, is inconclusive or negative. Recently, integrated PET/CT, in which a full-ring-detector clinical PET scanner and a multidetector helical CT scanner are combined, has enabled the acquisition of both metabolic and anatomic imaging data using one device in a single diagnostic session. This can also provide precise anatomic localization of suspicious areas of increased FDG uptake and rule out false-positive PET findings. FDG-PET/CT is an accurate modality for assessing primary and recurrent ovarian cancer and may affect management. FDG-PET/CT may provide benefits for detection of recurrent of ovarian cancer and improve surgical planning. And FDG-PET has been shown to predict response to neoadjuvant chemotherapy and survival in advanced ovarian cancer. This review focuses on the role of FDG-PET and FDG-PET/CT in the management of patients with ovarian cancer. Recently, we have evaluated 16α-18F-fluoro-17β-estradiol (FES)-PET, which detects estrogen receptors. In a preliminary study we reported that FES-PET provides information useful for assessing ER status in advanced ovarian cancer. This new information may expand treatment choice for such patients. PMID:19527525

  4. 18F-FDG positron autoradiography with a particle counting silicon pixel detector.

    PubMed

    Russo, P; Lauria, A; Mettivier, G; Montesi, M C; Marotta, M; Aloj, L; Lastoria, S

    2008-11-07

    We report on tests of a room-temperature particle counting silicon pixel detector of the Medipix2 series as the detector unit of a positron autoradiography (AR) system, for samples labelled with (18)F-FDG radiopharmaceutical used in PET studies. The silicon detector (1.98 cm(2) sensitive area, 300 microm thick) has high intrinsic resolution (55 microm pitch) and works by counting all hits in a pixel above a certain energy threshold. The present work extends the detector characterization with (18)F-FDG of a previous paper. We analysed the system's linearity, dynamic range, sensitivity, background count rate, noise, and its imaging performance on biological samples. Tests have been performed in the laboratory with (18)F-FDG drops (37-37 000 Bq initial activity) and ex vivo in a rat injected with 88.8 MBq of (18)F-FDG. Particles interacting in the detector volume produced a hit in a cluster of pixels whose mean size was 4.3 pixels/event at 11 keV threshold and 2.2 pixels/event at 37 keV threshold. Results show a sensitivity for beta(+) of 0.377 cps Bq(-1), a dynamic range of at least five orders of magnitude and a lower detection limit of 0.0015 Bq mm(-2). Real-time (18)F-FDG positron AR images have been obtained in 500-1000 s exposure time of thin (10-20 microm) slices of a rat brain and compared with 20 h film autoradiography of adjacent slices. The analysis of the image contrast and signal-to-noise ratio in a rat brain slice indicated that Poisson noise-limited imaging can be approached in short (e.g. 100 s) exposures, with approximately 100 Bq slice activity, and that the silicon pixel detector produced a higher image quality than film-based AR.

  5. 6-( sup 18 F)fluoro-L-dopa probes dopamine turnover rates in central dopaminergic structures

    SciTech Connect

    Barrio, J.R.; Huang, S.C.; Melega, W.P.; Yu, D.C.; Hoffman, J.M.; Schneider, J.S.; Satyamurthy, N.; Mazziotta, J.C.; Phelps, M.E. )

    1990-12-01

    6-({sup 18}F)Fluoro-L-DOPA (FDOPA) cerebral kinetics and metabolism were correlated in normal primates (Macaca nemestrina) and primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced unilateral Parkinsonism. Application of a tracer kinetic model to positron emission tomography (PET) data indicated that the model allows reliable estimation of FDOPA blood brain barrier transport, decarboxylation and release of stored 6-({sup 18}F)fluorodopamine (FDA) radioactivity in normal striatum (k4 = 0.005/min, turnover half-time greater than or equal to 2 hr), in agreement with biochemical data. PET scans of MPTP treated monkeys revealed 40-50% reduction in total striatal activity in comparison with pre-MPTP scans. Monkey brain biochemical analysis revealed that the reduction in activity was mainly due to a decrease in FDA and its metabolites, 6({sup 18}F)fluorohomovanillic (FHVA) and 6-({sup 18}F)fluoro-3, 4-dihydroxyphenylacetic acid (FDOPAC). The remaining activity in tissue was 3-0-methyl-6-({sup 18}F)fluoro-L-DOPA (3-OMFD) of peripheral origin. The (FHVA + FDOPAC)/FDA ratio was 1:2 in normal putamen and greater than or equal to 6:1 in the lesioned putamen, indicative of a dramatic increase in turnover of FDA. Both kinetic and biochemical data indicate that FDOPA labels a slow turnover rate pool of dopamine in rat and primate brain. This turnover rate for stored dopamine (DA) is accelerated with dopaminergic cell losses (e.g., MPTP-induced Parkinsonism).

  6. HPLC and TLC methods for analysis of [(18)F]FDG and its metabolites from biological samples.

    PubMed

    Rokka, Johanna; Grönroos, Tove J; Viljanen, Tapio; Solin, Olof; Haaparanta-Solin, Merja

    2017-03-24

    The most used positron emission tomography (PET) tracer, 2-[(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG), is a glucose analogue that is used to measure tissue glucose consumption. Traditionally, the Sokoloff model is the basis for [(18)F]FDG modeling. According to this model, [(18)F]FDG is expected to be trapped in a cell in the form of [(18)F]FDG-6-phosphate ([(18)F]FDG-6-P). However, several studies have shown that in tissues, [(18)F]FDG metabolism goes beyond [(18)F]FDG-6-P. Our aim was to develop radioHPLC and radioTLC methods for analysis of [(18)F]FDG metabolites from tissue samples. The radioHPLC method uses a sensitive on-line scintillation detector to detect radioactivity, and the radioTLC method employs digital autoradiography to detect the radioactivity distribution on a TLC plate. The HPLC and TLC methods were developed using enzymatically in vitro-produced metabolites of [(18)F]FDG as reference standards. For this purpose, three [(18)F]FDG metabolites were synthesized: [(18)F]FDG-6-P, [(18)F]FD-PGL, and [(18)F]FDG-1,6-P2. The two methods were evaluated by analyzing the [(18)F]FDG metabolic profile from rodent ex vivo tissue homogenates. The HPLC method with an on-line scintillation detector had a wide linearity in a range of 5Bq-5kBq (LOD 46Bq, LOQ 139Bq) and a good resolution (Rs ≥1.9), and separated [(18)F]FDG and its metabolites clearly. The TLC method combined with digital autoradiography had a high sensitivity in a wide range of radioactivity (0.1Bq-2kBq, LOD 0.24Bq, LOQ 0.31Bq), and multiple samples could be analyzed simultaneously. As our test and the method validation with ex vivo samples showed, both methods are useful, and at best they complement each other in analysis of [(18)F]FDG and its radioactive metabolites from biological samples.

  7. Enantioselective synthesis of 6-[fluorine-18]-fluro-l-dopa from no-carrier-added fluorine-18-fluoride

    SciTech Connect

    Lemaire, C.; Damhaut, P.; Plenvaux, A.

    1994-12-01

    A trimethylammonium veratraldehyde triflate was synthesized and used as a precursor for the asymmetric synthesis of 6-[{sup 18}F]fluoro-L-dopa. Its nucleophilic fluorination with {sup 18} F-fluoride produced by the {sup 18}O(p,n) {sup 18}F nuclear reaction on enriched {sup 18}O-water led to the corresponding no-carrier-added [{sup 18}F]fluoroveratraldehyde (45 {plus_minus} 5% EOB). Diiodosilane was used to prepare the corresponding [{sup 18}F] fluorobenzyl iodide (36.5 {plus_minus} 5.3% EOB). Alkylation of (S)-1-tert-boc-2-tert-butyl-3-methyl-4-imidazolidinone with this electrophilic agent, hydrolysis and purification by preparative high-pressure liquid chromatography made 6-[{sup 18}F]fluoro-L-dopa ready for human injection, in a 23% {plus_minus} 6% decay-corrected radiochemical yield. The enantiomeric purity and the specific activity were above 96% and 1 Cl/{mu}mole respectively. Through this procedure, starting from 250 mCi of {sup 18}F-fluoride, multimillicurie amounts (32 {plus_minus} 8.5 mCi) of no-carrier-added 6-[{sup 18}F]fluoro-L-dopa are now available at the end of synthesis (90 min) with a good radiochemical purity (more than 98%). 28 refs., 3 figs., 1 tab.

  8. Mapping of second-nearest-neighbor fluoride ions of orthorhombic Gd 3+-Ag + complexes in CaF 2

    NASA Astrophysics Data System (ADS)

    Nakata, R.; Den Hartog, H. W.

    The ENDOR technique is applied to determine the positions of 24 second-nearest-neighbor F - ions around an orthorhombic Gd 3+-Ag + complex in CaF 2 crystals. Experimental ENDOR data of the second-nearest-neighbor F - ions are analyzed by using the usual spin Hamiltonian and a least-squares fitting method. The best fits of the experimental results give superhyperfine (shf) constants and the F - directions ( K, L, M) with respect to the Gd 3+ ion, from which the distance between the second-nearest-neighbor F - ion and the Gd 3+ ion is determined by assuming that the hyperfine interaction is due to the classical dipole-dipole interaction. The displacements of the F - ions are estimated and compared with the theoretical values calculated by Bijvank and den Hartog on the basis of a polarizable point charge model.

  9. Bond Dissociation Energies of the Tungsten Fluorides and Their Singly-Charged Ions: A Density Functional Survey

    NASA Technical Reports Server (NTRS)

    Dyall, Kenneth G.; Arnold, James (Technical Monitor)

    1999-01-01

    The dissociation of WF6 and the related singly-charged cations and anions into the lower fluorides and fluorine atoms has been investigated theoretically using density functional theory (B3LYP) and relativistic effective core potentials, with estimates of spin-orbit effects included using a simple model. The inclusion of spin-orbit is essential for a correct description of the thermochemistry. The total atomization energy of the neutral and anionic WF6 is reproduced to within 25 kcal/mol, but comparison of individual bond dissociation energies with available experimental data shows discrepancies of up to 10 kcal/mol. The results are nevertheless useful to help resolve discrepancies in experimental data and provide estimates of missing data.

  10. Facile purification and click labeling with 2-[18F]fluoroethyl azide using solid phase extraction cartridges

    DOE PAGES

    Zhou, Dong; Chu, Wenhua; Peng, Xin; ...

    2014-11-04

    In this paper, a facile method was developed to purify 2-[18F]fluoroethyl azide ([18F]FEA) using a C18 cartridge and an Oasis® HLB cartridge in series, in which [18F]FEA was exclusively trapped on the HLB cartridge. [18F]FEA can be eluted for reactions in solution; alternatively click labeling can be carried out on the HLB cartridge itself by loading an alkyne substrate and copper (I) catalyst dissolved in DMF onto the cartridge. Finally, this solid phase extraction methodology for purification and click labeling with [18F]FEA, either in solution or on the cartridge, is safe, simple, reproducible in high yield, and compatible with automatedmore » synthesis of 18F-labeled PET tracers.« less

  11. Effect of Carbidopa on 18F-FDOPA Uptake in Insulinoma: From Cell Culture to Small-Animal PET Imaging.

    PubMed

    Detour, Julien; Pierre, Alice; Boisson, Fréderic; Kreutter, Guillaume; Lavaux, Thomas; Namer, Izzie Jacques; Kessler, Laurence; Brasse, David; Marchand, Patrice; Imperiale, Alessio

    2017-01-01

    Patient premedication with carbidopa seems to improve the accuracy of 6-(18)F-fluoro-3,4-dihydroxy-l-phenylalanine ((18)F-FDOPA) PET for insulinoma diagnosis. However, the risk of PET false-negative results in the presence of carbidopa is a concern. Consequently, we aimed to evaluate the effect of carbidopa on (18)F-FDOPA uptake in insulinoma β-cells and an insulinoma xenograft model in mice.

  12. Multicore-shell nanofiber architecture of polyimide/polyvinylidene fluoride blend for thermal and long-term stability of lithium ion battery separator.

    PubMed

    Park, Sejoon; Son, Chung Woo; Lee, Sungho; Kim, Dong Young; Park, Cheolmin; Eom, Kwang Sup; Fuller, Thomas F; Joh, Han-Ik; Jo, Seong Mu

    2016-11-11

    Li-ion battery, separator, multicoreshell structure, thermal stability, long-term stability. A nanofibrous membrane with multiple cores of polyimide (PI) in the shell of polyvinylidene fluoride (PVdF) was prepared using a facile one-pot electrospinning technique with a single nozzle. Unique multicore-shell (MCS) structure of the electrospun composite fibers was obtained, which resulted from electrospinning a phase-separated polymer composite solution. Multiple PI core fibrils with high molecular orientation were well-embedded across the cross-section and contributed remarkable thermal stabilities to the MCS membrane. Thus, no outbreaks were found in its dimension and ionic resistance up to 200 and 250 °C, respectively. Moreover, the MCS membrane (at ~200 °C), as a lithium ion battery (LIB) separator, showed superior thermal and electrochemical stabilities compared with a widely used commercial separator (~120 °C). The average capacity decay rate of LIB for 500 cycles was calculated to be approximately 0.030 mAh/g/cycle. This value demonstrated exceptional long-term stability compared with commercial LIBs and with two other types (single core-shell and co-electrospun separators incorporating with functionalized TiO2) of PI/PVdF composite separators. The proper architecture and synergy effects of multiple PI nanofibrils as a thermally stable polymer in the PVdF shell as electrolyte compatible polymers are responsible for the superior thermal performance and long-term stability of the LIB.

  13. Poly(vinylidene fluoride)/SiO2 composite membranes prepared by electrospinning and their excellent properties for nonwoven separators for lithium-ion batteries

    NASA Astrophysics Data System (ADS)

    Zhang, Feng; Ma, Xilan; Cao, Chuanbao; Li, Jili; Zhu, Youqi

    2014-04-01

    PVdF/SiO2 composite nonwoven membranes exhibiting high safety (thermal stability), high ionic conductivity and excellent electrochemical performances are firstly prepared by electrospinning poly(vinylidene fluoride) (PVdF) homopolymer and silicon dioxide (SiO2) sol synchronously for the separators of lithium-ion batteries (LIBs). Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and hot oven tests show that the PVdF/SiO2 composite nonwoven membranes are thermally stable at a high temperature of 400 °C while the commercial Celgard 2400 PP membrane exhibits great shrinkage at 130 °C, indicating a superior thermal stability of PVdF/SiO2 composite nonwoven membranes than that of Celgard membrane. Moreover, the composite membrane exhibits fairly high ionic conductivity (7.47 × 10-3 S cm-1) that significantly improves the performance of LIBs. The PVdF/SiO2 composite membranes are also evaluated to have higher level of porosity (75-85%) and electrolyte uptake (571-646 wt%), lower interfacial resistance compared to the Celgard separator. The lithium-ion cell (using LiFePO4 cathode) assembled with the composite membrane exhibits more stable cycle performance, higher discharge capacity (159 mAh g-1) and excellent capacity retention which proves that they are promising candidates for separators of high performance rechargeable LIBs.

  14. Multicore-shell nanofiber architecture of polyimide/polyvinylidene fluoride blend for thermal and long-term stability of lithium ion battery separator

    NASA Astrophysics Data System (ADS)

    Park, Sejoon; Son, Chung Woo; Lee, Sungho; Kim, Dong Young; Park, Cheolmin; Eom, Kwang Sup; Fuller, Thomas F.; Joh, Han-Ik; Jo, Seong Mu

    2016-11-01

    Li-ion battery, separator, multicoreshell structure, thermal stability, long-term stability. A nanofibrous membrane with multiple cores of polyimide (PI) in the shell of polyvinylidene fluoride (PVdF) was prepared using a facile one-pot electrospinning technique with a single nozzle. Unique multicore-shell (MCS) structure of the electrospun composite fibers was obtained, which resulted from electrospinning a phase-separated polymer composite solution. Multiple PI core fibrils with high molecular orientation were well-embedded across the cross-section and contributed remarkable thermal stabilities to the MCS membrane. Thus, no outbreaks were found in its dimension and ionic resistance up to 200 and 250 °C, respectively. Moreover, the MCS membrane (at ~200 °C), as a lithium ion battery (LIB) separator, showed superior thermal and electrochemical stabilities compared with a widely used commercial separator (~120 °C). The average capacity decay rate of LIB for 500 cycles was calculated to be approximately 0.030 mAh/g/cycle. This value demonstrated exceptional long-term stability compared with commercial LIBs and with two other types (single core-shell and co-electrospun separators incorporating with functionalized TiO2) of PI/PVdF composite separators. The proper architecture and synergy effects of multiple PI nanofibrils as a thermally stable polymer in the PVdF shell as electrolyte compatible polymers are responsible for the superior thermal performance and long-term stability of the LIB.

  15. Closely packed x-poly(ethylene glycol diacrylate) coated polyetherimide/poly(vinylidene fluoride) fiber separators for lithium ion batteries with enhanced thermostability and improved electrolyte wettability

    NASA Astrophysics Data System (ADS)

    Zhai, Yunyun; Xiao, Ke; Yu, Jianyong; Ding, Bin

    2016-09-01

    The x-polyethylene glycol diacrylate (x-PEGDA) coated polyetherimide/polyvinylidene fluoride (PEI/PVdF) membranes are obtained by the facile combination of dip-coating and free radical polymerization of PEGDA on the electrospun PEI/PVdF fiber membranes. Successful cross-linking of PEGDA increases the average fibers diameter from 553 to 817 nm and reduces the packing density, which not only increases the tensile strength of x-PEGDA coated PEI/PVdF membranes, but also decreases the average pore diameter. Besides, the x-PEGDA coated PEI/PVdF membranes are endowed with good wettability, high electrolyte uptake, high ionic conductivity and improved electrochemical stability window because of the good affinity of PEI and PEGDA with liquid electrolyte. Benefiting from the synergetic effect of PEI and PVdF, the x-PEGDA coated PEI/PVdF membranes exhibit excellent thermal stability and nonflammability, which are beneficial for enhancing the safety of lithium ion batteries. More importantly, the x-PEGDA coated PEI/PVdF membranes based Li/LiFePO4 cell exhibits comparable cycling stability with capacity retention of 95.9% after 70 cycles and better rate capability compared with the Celgard membrane based cell. The results clearly demonstrate that the x-PEGDA coated PEI/PVdF membranes are the promising separator candidate with improved wettability and safety for next-generation lithium ion batteries.

  16. Investigation of brain tumors using 18F-fluorobutyl ethacrynic amide and its metabolite with positron emission tomography

    PubMed Central

    Huang, Ying-Cheng; Huang, Ho-Lien; Yeh, Chun-Nan; Lin, Kun-Ju; Yu, Chung-Shan

    2015-01-01

    To date, imaging of malignant glioma remains challenging. In positron emission tomography-related diagnostic imaging, differential tumor uptake of 3′-deoxy-3′-[18F] fluorothymidine ([18F]FLT) has been shown to reflect the levels of cell proliferation and DNA synthesis. However, additional biomarkers for tumors are urgently required. Aberrant levels of glutathione transferase (GST) activity have been hypothesized to constitute such a novel diagnostic marker. Here, a C6 rat glioma tumor model was used to assess the ability of the positron emission tomography tracers, [18F]FLT and 18F-fluorobutyl ethacrynic amide ([18F]FBuEA), to indicate reactive oxygen species-induced stress responses as well as detoxification-related processes in tumors. Using a GST activity assay, we were able to demonstrate that FBuEA is more readily catalyzed by GST-π than by GST-α. Furthermore, we showed that FBuEA-GS, a metabolite of FBuEA, elicits greater cytotoxicity in tumor cells than in normal fibroblast cells. Finally, in vitro and in vivo investigation of radiotracer distribution of [18F]FBuEA and [18F] FBuEA-GS revealed preferential accumulation in C6 glioma tumor cells over normal fibroblast cells for [18F]FBuEA-GS but not for [18F]FBuEA. PMID:26244025

  17. Comparison between kinetic modelling and graphical analysis for the quantification of [18F]fluoromethylcholine uptake in mice

    PubMed Central

    2013-01-01

    Background Until now, no kinetic model was described for the oncologic tracer [18F]fluoromethylcholine ([18F]FCho), so it was aimed to validate a proper model, which is easy to implement and allows tracer quantification in tissues. Methods Based on the metabolic profile, two types of compartmental models were evaluated. One is a 3C2i model, which contains three tissue compartments and two input functions and corrects for possible [18F]fluorobetaine ([18F]FBet) uptake by the tissues. On the other hand, a two-tissue-compartment model (2C1i) was evaluated. Moreover, a comparison, based on intra-observer variability, was made between kinetic modelling and graphical analysis. Results Determination of the [18F]FCho-to-[18F]FBet uptake ratios in tissues and evaluation of the fitting of both kinetic models indicated that corrections for [18F]FBet uptake are not mandatory. In addition, [18F]FCho uptake is well described by the 2C1i model and by graphical analysis by means of the Patlak plot. Conclusions The Patlak plot is a reliable, precise, and robust method to quantify [18F]FCho uptake independent of scan time or plasma clearance. In addition, it is easily implemented, even under non-equilibrium conditions and without creating additional errors. PMID:24034278

  18. Preclinical acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [(18)F]fluorocholine in mice.

    PubMed

    Silveira, Marina B; Ferreira, Soraya M Z M D; Nascimento, Leonardo T C; Costa, Flávia M; Mendes, Bruno M; Ferreira, Andrea V; Malamut, Carlos; Silva, Juliana B; Mamede, Marcelo

    2016-10-01

    [(18)F]Fluorocholine ([(18)F]FCH) has been proven to be effective in prostate cancer. Since [(18)F]FCH is classified as a new radiopharmaceutical in Brazil, preclinical safety and efficacy data are required to support clinical trials and to obtain its approval. The aim of this work was to perform acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [(18)F]FCH. The results could support its use in nuclear medicine as an important piece of work for regulatory in Brazil.

  19. Alterations in 18F-FDG accumulation into neck-related muscles after neck dissection for patients with oral cancers

    PubMed Central

    Kito, Shinji; Koga, Hirofumi; Kodama, Masaaki; Habu, Manabu; Kokuryo, Shinya; Oda, Masafumi; Matsuo, Kou; Nishino, Takanobu; Matsumoto-Takeda, Shinobu; Uehara, Masataka; Yoshiga, Daigo; Tanaka, Tatsurou; Nishimura, Shun; Miyamoto, Ikuya; Sasaguri, Masaaki; Tominaga, Kazuhiro; Yoshioka, Izumi; Morimoto, Yasuhiro

    2016-01-01

    Background 18F-fluoro-2-deoxy-D-glucose (18F-FDG) accumulations are commonly seen in the neck-related muscles of the surgical and non-surgical sides after surgery with neck dissection (ND) for oral cancers, which leads to radiologists having difficulty in diagnosing the lesions. To examine the alterations in 18F-FDG accumulation in neck-related muscles of patients after ND for oral cancer. Material and Methods 18F-FDG accumulations on positron emission tomography (PET)-computed tomography (CT) in neck-related muscles were retrospectively analyzed after surgical dissection of cervical lymph nodes in oral cancers. Results According to the extent of ND of cervical lymph nodes, the rate of patients with 18F-FDG-PET-positive areas increased in the trapezius, sternocleidomastoid, and posterior neck muscles of the surgical and/or non-surgical sides. In addition, SUVmax of 18F-FDG-PET-positive areas in the trapezius and sternocleidomastoid muscles were increased according to the extent of the ND. Conclusions In evaluating 18F-FDG accumulations after ND for oral cancers, we should pay attention to the 18F-FDG distributions in neck-related muscles including the non-surgical side as false-positive findings. Key words:18F-FDG, PET-CT, oral cancers, muscles. PMID:27031062

  20. A simplified synthesis of the hypoxia imaging agent 2-(2-Nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-[18F]pentafluoropropyl)-acetamide ([18F]EF5)

    PubMed Central

    Chitneni, Satish K.; Bida, Gerald T.; Dewhirst, Mark W.; Zalutsky, Michael R.

    2012-01-01

    Introduction [18F]EF5 is a validated marker for PET imaging of tumor hypoxia. It is prepared by reacting a trifluoroallyl precursor with carrier-added [18F]F2 gas in trifluoroacetic acid (TFA) solvent. We report here an improved radiosynthesis and purification of [18F]EF5 by utilizing an electroformed nickel (Ni) target for [18F] F2 production, and Oasis® HLB cartridges for on-line solid phase extraction of [18F]EF5 prior to HPLC purification. Methods [18F]F2 was produced by deuteron bombardment of neon plus F2 in an Ni target, and bubbled through the radiolabelling precursor solution. Purification was achieved by extracting the contents of the crude reaction mixture onto Oasis HLB cartridges, and subsequently eluted onto a semi-preparative HPLC column for further separation. Purified [18F]EF5 was evaluated in small animal PET studies using HCT116 tumor xenografts in nude mice. Results The electroformed Ni target enabled recovery of >75% of the radioactivity from the cyclotron target, resulting in 16.2±2.2 GBq (438±58 mCi) of [18F]F2 available for the synthesis. Use of Oasis cartridges yielded a less complex mixture for purification. On average, 1140±200 MBq (30.8±5.4 mCi) of [18F]EF5 were collected at EOS. Small animal PET imaging studies showed specific retention of [18F]EF5 in tumors, with tumor-to-muscle ratios of 2.7±0.3 at about 160 min after injection. Conclusion A simple procedure has been developed for the routine synthesis of [18F]EF5 in amounts and purity required for clinical studies. This new method avoids the need for TFA evaporation and also enables facile automation of the synthesis using commercially available radiosynthesis modules. PMID:22727821

  1. Marmoset Serotonin 5-HT1A Receptor Mapping with a Biased Agonist PET Probe 18F-F13714: Comparison with an Antagonist Tracer 18F-MPPF in Awake and Anesthetized States

    PubMed Central

    Yokoyama, Chihiro; Mawatari, Aya; Kawasaki, Akihiro; Takeda, Chiho; Onoe, Kayo; Doi, Hisashi; Newman-Tancredi, Adrian; Zimmer, Luc

    2016-01-01

    Background: In vivo mapping by positron emission tomography of the serotonin 1A receptors has been hindered by the lack of suitable agonist positron emission tomography probes. 18F-labeled F13714 is a recently developed biased agonist positron emission tomography probe that preferentially targets subpopulations of serotonin 1A receptors in their “active state,” but its brain labeling pattern in nonhuman primate has not been described. In addition, a potential confound in the translatability of PET data between nonhuman animal and human arise from the use of anesthetics that may modify the binding profiles of target receptors. Methods: Positron emission tomography scans were conducted in a cohort of common marmosets (n=4) using the serotonin 1A receptor biased agonist radiotracer, 18F-F13714, compared with a well-characterized 18F-labeled antagonist radiotracer, 18F-MPPF. Experiments on each animal were performed under both consciousness and isoflurane-anesthesia conditions. Results: 18F-F13714 binding distribution in marmosets by positron emission tomography differs markedly from that of the 18F-MPPF. Whereas 18F-MPPF showed highest binding in hippocampus and amygdala, 18F-F13714 showed highest labeling in other regions, including insular and cingulate cortex, thalamus, raphe, caudate nucleus, and putamen. The binding potential values of 18F-F13714 were about one-third of those observed with 18F-MPPF, with marked individual- and region-specific differences under isoflurane-anesthetized vs conscious conditions. Conclusions: These findings highlight the importance of investigating the brain imaging of serotonin 1A receptors using agonist probes such as 18F-F13714, which may preferentially target subpopulations of serotonin 1A receptors in specific brain regions of nonhuman primate as a biased agonist. PMID:27608810

  2. (18)F-FBHGal for asialoglycoprotein receptor imaging in a hepatic fibrosis mouse model.

    PubMed

    Kao, Hao-Wen; Chen, Chuan-Lin; Chang, Wen-Yi; Chen, Jenn-Tzong; Lin, Wuu-Jyh; Liu, Ren-Shyan; Wang, Hsin-Ell

    2013-02-15

    Quantification of the expression of asialoglycoprotein receptor (ASGPR), which is located on the hepatocyte membrane with high-affinity for galactose residues, can help assess ASGPR-related liver diseases. A hepatic fibrosis mouse model with lower asialoglycoprotein receptor expression was established by dimethylnitrosamine (DMN) administration. This study developed and demonstrated that 4-(18)F-fluoro-N-(6-((3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)hexyl)benzamide ((18)F-FBHGal), a new (18)F-labeled monovalent galactose derivative, is an asialoglycoprotein receptor (ASGPR)-specific PET probe in a normal and a hepatic fibrosis mouse models. Immunoassay exhibited a linear correlation between the accumulation of GalH-FITC, a fluorescent surrogate of FBHGal, and the amount of ASGPR. A significant reduction in HepG2 cellular uptake (P <0.0001) was observed using confocal microscopy when co-incubated with 0.5μM of asialofetuin, a well known ASGPR blocking agent. Animal studies showed the accumulation of (18)F-FBHGal in fibrosis liver (14.84±1.10 %ID/g) was appreciably decreased compared with that in normal liver (20.50±1.51 %ID/g, P <0.01) at 30min post-injection. The receptor indexes (liver/liver-plus-heart ratio at 30min post-injection) of hepatic fibrosis mice derived from both microPET imaging and biodistribution study were significantly lower (P <0.01) than those of normal mice. The pharmacokinetic parameters (T(1/2)α, T(1/2)β, AUC and Cl) derived from microPET images revealed prolonged systemic circulation of (18)F-FBHGal in hepatic fibrosis mice compared to that in normal mice. The findings in biological characterizations suggest that (18)F-FBHGal is a feasible agent for PET imaging of hepatic fibrosis in mice and may provide new insights into ASGPR-related liver dysfunction.

  3. Quantification of dopamine transporter density with [18F]FECNT PET in healthy humans

    PubMed Central

    Nye, Jonathon A.; Votaw, John R.; Bremner, J. Douglas; Davis, Margaret R.; Voll, Ronald J.; Camp, Vernon M.; Goodman, Mark M.

    2015-01-01

    Introduction Fluorine-18 labeled 2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane ([18 F]FECNT) binds reversibly to the dopamine transporter (DAT) with high selectivity. [18 F]FECNT has been used extensively in the quantification of DAT occupancy in non-human primate brain and can distinguish between Parkinson's and healthy controls in humans. The purpose of this work was to develop a compartment model to characterize the kinetics of [18 F]FECNT for quantification of DAT density in healthy human brain. Methods Twelve healthy volunteers underwent 180 min dynamic [18 F]FECNT PET imaging including sampling of arterial blood. Regional time-activity curves were extracted from the caudate, putamen and midbrain including a reference region placed in the cerebellum. Binding potential, BPND, was calculated for all regions using kinetic parameters estimated from compartmental and Logan graphical model fits to the time-activity data. Simulations were performed to determine whether the compartment model could reliably fit time-activity data over a range of BPND values. Results The kinetics of [18 F]FECNT were well-described by the reversible 2-tissue arterial input and full reference tissue compartment models. Calculated binding potentials in the caudate, putamen and midbrain were in good agreement between the arterial input model, reference tissue model and the Logan graphical model. The distribution volume in the cerebellum did not reach a plateau over the duration of the study, which may be a result of non-specific binding in the cerebellum. Simulations that included non-specific binding show that the reference and arterial input models are able to estimate BPND for DAT densities well below that observed in normal volunteers. Conclusion The kinetics of [18 F]FECNT in human brain are well-described by arterial input and reference tissue compartment models. Measured and simulated data show that BPND calculated with reference tissue model is proportional to

  4. Measurement of radiative proton capture on 18F and implications for oxygen-neon novae reexamined

    NASA Astrophysics Data System (ADS)

    Akers, C.; Laird, A. M.; Fulton, B. R.; Ruiz, C.; Bardayan, D. W.; Buchmann, L.; Christian, G.; Davids, B.; Erikson, L.; Fallis, J.; Hager, U.; Hutcheon, D.; Martin, L.; Murphy, A. St. J.; Nelson, K.; Ottewell, D.; Rojas, A.; Spyrou, A.

    2016-12-01

    Background: The rate of the 18F(p ,γ )19Ne reaction affects the final abundance of the radioisotope 18F ejected from novae. This nucleus is important as its abundance is thought to significantly influence the first-stage 511-keV and continuum γ -ray emission in the aftermath of novae. No successful measurement of this reaction existed prior to this work, and the rate used in stellar models had been calculated based on incomplete information from contributing resonances. Purpose: Of the two resonances thought to provide a significant contribution to the astrophysical reaction rate, located at Ec .m .=330 and 665 keV, the former has a radiative width estimated from the assumed analog state in the mirror nucleus, 19F, while the latter resonance does not have an analog state assignment, resulting in an arbitrary radiative width being assumed. As such, a direct measurement was needed to establish what role this resonance plays in the destruction of 18F at nova temperatures. This paper extends and takes the place of a previous Letter which reported the strength of the Ec .m .=665 keV resonance. Method: The DRAGON recoil separator was used to directly measure the strength of the important 665-keV resonance in this reaction, in inverse kinematics, by observing 19Ne reaction products. A radioactive 18F beam was provided by the ISAC facility at TRIUMF. R -matrix calculations were subsequently used to evaluate the significance of the results at astrophysical energies. Results: We report the direct measurement of the 18F(p ,γ )19Ne reaction with the reevaluation of several detector efficiencies and the use of an updated 19Ne level scheme in the reaction rate analysis. The strength of the 665-keV resonance (Ex=7.076 MeV) is found to be an order of magnitude weaker than currently assumed in nova models. An improved analysis of the previously reported data is presented here, resulting in a slightly different value for the resonance strength. These small changes, however, do

  5. Synthesis of [{sup 18}F]Ro41-0960, a potent COMT inhibitor, for use in vivo mapping with PET

    SciTech Connect

    Ding, Y.S.; Sugano, Y.; Gatley, S.J.

    1995-05-01

    Catechol-O-methyltransferase (COMPT; EC 2.1.1.6) is one of the two major enzymes which metabolize the catecholamine neurotransmitters. It is distributed throughout the body and brain and is elevated in breast cancer tissue when it plays a role in estrogen metabolism. It is also an important molecular target in the development of drugs to treat Parkinson`s disease (PD). Because COMT regulates the concentration of important neurotransmitter amines such as dopamine, there is speculation that abnormalities in its activity may be associated with neurological, and psychiatric disorders. Ro41-9060(3,4-dihydroxy-5-nitro-2{prime}-fluorobenzophenone) is a potent, fluorine containing COMT inhibitor which has been reported to cross the blood brain barrier. It is structurally similar to Ro40-7592 which is currently undergoing clinical trials in PD. We report the synthesis of [{sup 18}F]Ro41-0960, for investigation for mapping COMT and for studies of COMT drugs. [{sup 18}F]Ro41-0960 was synthesized by the nucleophilic aromatic substitution reaction with NCA [{sup 18}F] fluoride on a protected precursor (prepared via a five-step synthesis) followed by hydrolysis with HBr (synthesis time of 100 min; radiochemical yield of 5-7% (EOB)). Though Ro41-0960 has been reported to cross the blood brain barrier, PET studies in baboon demonstrated that an almost complete absence of the drug from the brain both at tracer doses and with the addition of unlabeled drug (1.5 mg/kg) at all times through a 90 min experimental interval. The plasma to brain ratios of F-18 average about 40:1. However, high uptake was observed in the kidneys and in other organs which are known to have high COMT. Studies in mice showed that at 30 min after injection of tracer, F-18 in kidneys was largely as [{sup 18}F]Ro-41-0960 and that it could be displaced with unlabeled Ro41-0960. These studies provide the first example of a positron emitter labeled COMT radiotracer.

  6. A dual-tracer study of extrastriatal 6-[18F]fluoro-m-tyrosine and 6-[18F]-fluoro-L-dopa uptake in Parkinson's disease.

    PubMed

    Li, Clarence T; Palotti, Matthew; Holden, James E; Oh, Jen; Okonkwo, Ozioma; Christian, Bradley T; Bendlin, Barbara B; Buyan-Dent, Laura; Harding, Sandra J; Stone, Charles K; DeJesus, Onofre T; Nickles, Robert J; Gallagher, Catherine L

    2014-08-01

    6-[(18)F]-Fluoro-L-dopa (FDOPA) has been widely used as a biomarker for catecholamine synthesis, storage, and metabolism--its intense uptake in the striatum, and fainter uptake in other brain regions, is correlated with the symptoms and pathophysiology of Parkinson's disease (PD). 6-[(18)F]fluoro-m-tyrosine (FMT), which also targets L-amino acid decarboxylase, has potential advantages over FDOPA as a radiotracer because it does not form catechol-O-methyltransferase (COMT) metabolites. The purpose of the present study was to compare the regional distribution of these radiotracers in the brains of PD patients. Fifteen Parkinson's patients were studied with FMT and FDOPA positron emission tomography (PET) as well as high-resolution structural magnetic resonance imaging (MRI). MRI's were automatically parcellated into neuroanatomical regions of interest (ROIs) in Freesurfer (http://surfer.nmr.mgh.harvard.edu); region-specific uptake rate constants (Kocc) were generated from coregistered PET using a Patlak graphical approach. The essential findings were as follows: (1) regional Kocc were highly correlated between the radiotracers and in agreement with a previous FDOPA studies that used different ROI selection techniques; (2) FMT Kocc were higher in extrastriatal regions of relatively large uptake such as amygdala, pallidum, brainstem, hippocampus, entorhinal cortex, and thalamus, whereas cortical Kocc were similar between radiotracers; (3) while subcortical uptake of both radiotracers was related to disease duration and severity, cortical uptake was not. These results suggest that FMT may have advantages for examining pathologic changes within allocortical loop structures, which may contribute to cognitive and emotional symptoms of PD.

  7. N-Succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ([18F]SFBTMGMB): A Residualizing Label for 18F-labeling of internalizing biomolecules

    PubMed Central

    Vaidyanathan, Ganesan; McDougald, Darryl; Choi, Jaeyeon; Pruszynski, Marek; Koumarianou, Eftychia; Zhou, Zhengyuan; Zalutsky, Michael R.

    2015-01-01

    Residualizing labeling methods for internalizing peptides and proteins are designed to trap the radionuclide inside the cell after intracellular degradation of the biomolecule. The goal of this work was to develop a residualizing label for the 18F-labeling of internalizing biomolecules based on a template used successfully for radioiodination. N-succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(bis-Boc-guanidinomethyl)benzoate (Boc2-[18F]SFBTMGMB) was synthesized by click reaction of an azide precursor and [18F]fluorohexyne in 8.5 ± 2.8% average decay-corrected radiochemical yield (n =15). An anti-HER2 nanobody 5F7 was labeled with 18F using [18F]SFBTMGMB ([18F]RL-I), obtained by the deprotection of Boc2-[18F]SFBTMGMB, in 31.2 ± 6.7% (n =5) conjugation efficiency. Thus labeled nanobody had a radiochemical purity of >95%, bound to the HER2-expressing BT474M1 breast cancer cells with an affinity of 4.7 ± 0.9 nM, and had an immunoreactive fraction of 62–80%. In summary, a novel residualizing prosthetic agent for labeling biomolecules with 18F has been developed. An anti-HER2 nanobody was labeled using this prosthetic group with retention of affinity and immunoreactivity to HER2. PMID:26645790

  8. Radiolabeled amino acids for tumor imaging with PET: radiosynthesis and biological evaluation of 2-amino-3-[18F]fluoro-2-methylpropanoic acid and 3-[18F]fluoro-2-methyl-2-(methylamino)propanoic acid.

    PubMed

    McConathy, Jonathan; Martarello, Laurent; Malveaux, Eugene J; Camp, Vernon M; Simpson, Nicholas E; Simpson, Chiab P; Bowers, Geoffrey D; Olson, Jeffrey J; Goodman, Mark M

    2002-05-23

    Novel radiopharmaceuticals, including amino acids, that target neoplasms through their altered metabolic states have shown promising results in preclinical and clinical studies. Two fluorinated analogues of alpha-aminoisobutyric acid, 2-amino-3-fluoro-2-methylpropanoic acid (FAMP) and 3-fluoro-2-methyl-2-(methylamino)propanoic acid (N-MeFAMP), have been radiolabeled with fluorine-18, characterized in amino acid uptake assays, and evaluated in vivo in normal rats and a rodent tumor model. The key steps in the syntheses of both radiotracers involved the preparation of cyclic sulfamidate precursors. Radiosyntheses of both [18F]FAMP and [18F]N-MeFAMP via no-carrier-added nucleophilic substitution provided high yields (>78% decay-corrected) in high radiochemical purity (>99%). Amino acid transport assays using 9L gliosarcoma cells demonstrated that both compounds are substrates for the A type amino acid transport system, with [18F]N-MeFAMP showing higher specificity than [18F]FAMP for A type transport. Tissue distribution studies in normal Fischer rats and Fischer rats implanted intracranially with 9L gliosarcoma tumor cells were also performed. At 60 min postinjection, the tumor vs normal brain ratio of radioactivity was 36:1 in animals receiving [18F]FAMP and 104:1 in animals receiving [18F]N-MeFAMP. On the basis of these studies, both [18F]FAMP and [18F]N-MeFAMP are promising imaging agents for the detection of intracranial neoplasms via positron emission tomography.

  9. Automated production at the curie level of no-carrier-added 6-[(18)F]fluoro-L-dopa and 2-[(18)F]fluoro-L-tyrosine on a FASTlab synthesizer.

    PubMed

    Lemaire, C; Libert, L; Franci, X; Genon, J-L; Kuci, S; Giacomelli, F; Luxen, A

    2015-06-15

    An efficient, fully automated, enantioselective multi-step synthesis of no-carrier-added (nca) 6-[(18)F]fluoro-L-dopa ([(18)F]FDOPA) and 2-[(18)F]fluoro-L-tyrosine ([(18)F]FTYR) on a GE FASTlab synthesizer in conjunction with an additional high- performance liquid chromatography (HPLC) purification has been developed. A PTC (phase-transfer catalyst) strategy was used to synthesize these two important radiopharmaceuticals. According to recent chemistry improvements, automation of the whole process was implemented in a commercially available GE FASTlab module, with slight hardware modification using single use cassettes and stand-alone HPLC. [(18)F]FDOPA and [(18)F]FTYR were produced in 36.3 ± 3.0% (n = 8) and 50.5 ± 2.7% (n = 10) FASTlab radiochemical yield (decay corrected). The automated radiosynthesis on the FASTlab module requires about 52 min. Total synthesis time including HPLC purification and formulation was about 62 min. Enantiomeric excesses for these two aromatic amino acids were always >95%, and the specific activity of was >740 GBq/µmol. This automated synthesis provides high amount of [(18)F]FDOPA and [(18)F]FTYR (>37 GBq end of synthesis (EOS)). The process, fully adaptable for reliable production across multiple PET sites, could be readily implemented into a clinical good manufacturing process (GMP) environment.

  10. Synthesis, radiolabeling, and biological evaluation of (R)- and (S)-2-amino-5-[18F]fluoro-2-methylpentanoic acid ((R)-, (S)-[18F]FAMPe) as potential positron emission tomography tracers for brain tumors

    DOE PAGES

    Bouhlel, Ahlem; Zhou, Dong; Li, Aixiao; ...

    2015-04-06

    In this paper, a novel 18F-labeled α,α-disubstituted amino acid-based tracer, 2-amino-5-[18F]fluoro-2-methylpentanoic acid ([18F]FAMPe), has been developed for brain tumor imaging with a longer alkyl side chain than previously reported compounds to increase brain availability via system L amino acid transport. Both enantiomers of [18F]FAMPe were obtained in good radiochemical yield (24–52% n = 8) and high radiochemical purity (>99%). In vitro uptake assays in mouse DBT gliomas cells revealed that (S)-[18F]FAMPe enters cells partly via sodium-independent system L transporters and also via other nonsystem A transport systems including transporters that recognize glutamine. Biodistribution and small animal PET/CT studies in themore » mouse DBT model of glioblastoma showed that both (R)- and (S)-[18F]FAMPe have good tumor imaging properties with the (S)-enantiomer providing higher tumor uptake and tumor to brain ratios. Finally, comparison of the SUVs showed that (S)-[18F]FAMPe had higher tumor to brain ratios compared to (S)-[18F]FET, a well-established system L substrate.« less

  11. A Review of NIST Primary Activity Standards for (18)F: 1982 to 2013.

    PubMed

    Bergeron, Denis E; Cessna, Jeffrey T; Coursey, Bert M; Fitzgerald, Ryan; Zimmerman, Brian E

    2014-01-01

    The new NIST activity standardization for (18)F, described in 2014 in Applied Radiation and Isotopes (v. 85, p. 77), differs from results obtained between 1998 and 2008 by 4 %. The new results are considered to be very reliable; they are based on a battery of robust primary measurement techniques and bring the NIST standard into accord with other national metrology institutes. This paper reviews all ten (18)F activity standardizations performed at NIST from 1982 to 2013, with a focus on experimental variables that might account for discrepancies. We have identified many possible sources of measurement bias and eliminated most of them, but we have not adequately accounted for the 1998-2008 results.

  12. Investigation of Nd3+ ions spectroscopic and laser properties in SrF2 fluoride single crystal

    NASA Astrophysics Data System (ADS)

    Alimov, O. K.; Basiev, T. T.; Doroshenko, M. E.; Fedorov, P. P.; Konyushkin, V. A.; Nakladov, A. N.; Osiko, V. V.

    2012-03-01

    The laser properties of SrF2:Nd3+ crystal with neodymium ions concentration of 0.5 at.% were investigated under diode laser pumping. Using temperature tuning of laser diode pumping wavelength two different lines centered at about 1037 nm and 1044 nm attributed to oscillation of different optical centers were obtained. The maximum lasing slope efficiency of 37% was obtained. The absorption and fluorescence spectra of different individual and clustered Nd3+ ions optical centers were observed depending on Nd3+ concentration. The lifetimes of the high symmetry L-centers were measured and found to be two orders of magnitude longer than that for clustered M-centers at room temperature. The lifetimes of M-centers at different temperatures were measured and microparameter of ion-ion interaction in Nd-pairs was determined.

  13. Fluorescent sensing of fluoride in cellular system.

    PubMed

    Jiao, Yang; Zhu, Baocun; Chen, Jihua; Duan, Xiaohong

    2015-01-01

    Fluoride ions have the important roles in a lot of physiological activities related with biological and medical system, such as water fluoridation, caries treatment, and bone disease treatment. Great efforts have been made to develop new methods and strategies for F(-) detection in the past decades. Traditional methods for the detection of F(-) including ion chromatography, ion-selective electrodes, and spectroscopic techniques have the limitations in the biomedicine research. The fluorescent probes for F(-) are very promising that overcome some drawbacks of traditional fluoride detection methods. These probes exhibit high selectivity, high sensitivity as well as quick response to the detection of fluoride anions. The review commences with a brief description of photophysical mechanisms for fluorescent probes for fluoride, including photo induced electron transfer (PET), intramolecular charge transfer (ICT), fluorescence resonance energy transfer (FRET), and excited-state intramolecular proton transfer (ESIPT). Followed by a discussion about common dyes for fluorescent fluoride probes, such as anthracene, naphalimide, pyrene, BODIPY, fluorescein, rhodamine, resorufin, coumarin, cyanine, and near-infrared (NIR) dyes. We divide the fluorescent probes for fluoride in cellular application systems into nine groups, for example, type of hydrogen bonds, type of cleavage of Si-O bonds, type of Si-O bond cleavage and cylization reactions, etc. We also review the recent reported carriers in the delivery of fluorescent fluoride probes. Seventy-four typical fluorescent fluoride probes are listed and compared in detail, including quantum yield, reaction medium, excitation and emission wavelengths, linear detection range, selectivity for F(-), mechanism, and analytical applications. Finally, we discuss the future challenges of the application of fluorescent fluoride probes in cellular system and in vivo. We wish that more and more excellent fluorescent fluoride probes will be

  14. Fluorescent Sensing of Fluoride in Cellular System

    PubMed Central

    Jiao, Yang; Zhu, Baocun; Chen, Jihua; Duan, Xiaohong

    2015-01-01

    Fluoride ions have the important roles in a lot of physiological activities related with biological and medical system, such as water fluoridation, caries treatment, and bone disease treatment. Great efforts have been made to develop new methods and strategies for F- detection in the past decades. Traditional methods for the detection of F- including ion chromatography, ion-selective electrodes, and spectroscopic techniques have the limitations in the biomedicine research. The fluorescent probes for F- are very promising that overcome some drawbacks of traditional fluoride detection methods. These probes exhibit high selectivity, high sensitivity as well as quick response to the detection of fluoride anions. The review commences with a brief description of photophysical mechanisms for fluorescent probes for fluoride, including photo induced electron transfer (PET), intramolecular charge transfer (ICT), fluorescence resonance energy transfer (FRET), and excited-state intramolecular proton transfer (ESIPT). Followed by a discussion about common dyes for fluorescent fluoride probes, such as anthracene, naphalimide, pyrene, BODIPY, fluorescein, rhodamine, resorufin, coumarin, cyanine, and near-infrared (NIR) dyes. We divide the fluorescent probes for fluoride in cellular application systems into nine groups, for example, type of hydrogen bonds, type of cleavage of Si-O bonds, type of Si-O bond cleavage and cylization reactions, etc. We also review the recent reported carriers in the delivery of fluorescent fluoride probes. Seventy-four typical fluorescent fluoride probes are listed and compared in detail, including quantum yield, reaction medium, excitation and emission wavelengths, linear detection range, selectivity for F-, mechanism, and analytical applications. Finally, we discuss the future challenges of the application of fluorescent fluoride probes in cellular system and in vivo. We wish that more and more excellent fluorescent fluoride probes will be developed

  15. A graphene loading heterogeneous hydrated forms iron based fluoride nanocomposite as novel and high-capacity cathode material for lithium/sodium ion batteries

    NASA Astrophysics Data System (ADS)

    Shen, Yongqiang; Wang, Xianyou; Hu, Hai; Jiang, Miaoling; Yang, Xiukang; Shu, Hongbo

    2015-06-01

    A graphene loading heterogeneous hydrated forms iron based fluoride (abbreviated as FeF3·xH2O/G) nanocomposite is successfully designed and synthesized for the first time by a sol-gel method. It found that the FeF3·xH2O nanoparticles distribute randomly on the surface of the graphene, stacking together to form a nanocomposite with high specific surface and abundant mesporous structure. The FeF3·xH2O was consisted of FeF3·3H2O and FeF2.5·0.5H2O with pyrochlore phase structure and FeF3·0.33H2O with hexagonal-tungsten-bronze-type structure (HTB). The FeF3·xH2O/G was used as cathode materials of rechargeable lithium/sodium batteries, respectively. It has been found that it can deliver a large reversible capacity exceeding 200 mAh g-1 and excellent cyclic performance with a residual capacity of 183 mAh g-1 after 100 cycles at 0.2C and 149 mAh g-1 after 200 cycles at 1C, especially, an outstanding rate performance exceeding 130 mAh g-1 at 5C in the voltage range of 1.5-4.5 V for Li-ion batteries. Moreover, when FeF3·xH2O/G is used as cathode material of Na-ion batteries, it exhibits also a high reversible capacity of 101 mAh g-1 after 30 cycles in the voltage range of 1.0-4.0 V at 0.1C. Therefore, FeF3·xH2O/G will a promising cathode material for high-performance lithium/sodium ion batteries.

  16. Calibration of the Capintec CRC-712M dose calibrator for (18)F.

    PubMed

    Mo, L; Reinhard, M I; Davies, J B; Alexiev, D; Baldock, C

    2006-04-01

    Primary standardisation was performed on a solution of (18)F using the 4pibeta-gamma coincidence counting efficiency-tracing extrapolation method with (60)Co used as a tracer nuclide. The result was used to calibrate the ANSTO secondary standard ionisation chamber which is used to disseminate Australian activity standards for gamma emitters. Using the secondary activity standard for (18)F, the Capintec CRC-712M dose calibrator at the Australian National Medical Cyclotron (NMC) Positron Emission Tomography (PET) Quality Control (QC) Section was calibrated. The dial setting number recommended by the manufacturer for the measurement of the activity of (18)F is 439. In this work, the dial setting numbers for the activity measurement of the solution of (18)F in Wheaton vials were experimentally determined to be 443+/-12, 446+/-12, 459+/-11, 473+/-15 for 0.1, 1, 4.5 and 9ml solution volumes, respectively. The uncertainties given above are expanded uncertainties (k=2) giving an estimated level of confidence of 95%. The activities determined using the manufacturer recommended setting number 439 are 0.8%, 1.4%, 4.0% and 6.5% higher than the standardised activities, respectively. It is recommended that a single dial setting number of 459 determined for 4.5ml is used for 0.1-9ml solution in Wheaton vials in order to simplify the operation procedure. With this setting the expended uncertainty (k=2) in the activity readout from the Capintec dose calibrator would be less than 6.2%.

  17. (18)F-FDG PET/CT findings in a case with HIV (-) Kaposi sarcoma.

    PubMed

    Ozdemir, E; Poyraz, N Y; Keskin, M; Kandemir, Z; Turkolmez, S

    2014-01-01

    Although mucocutaneous sites are the most frequently encountered sites of involvement, Kaposi Sarcoma (KS) may also occasionally involve the breast and the skeletal, endocrine, urinary and nervous systems.. Various imaging modalities may be used to delineate the extent of the disease by detecting unexpected sites of involvement. Herein, we report a case of classical type KS, in whom staging with (18)F-FDG PET/CT imaging disclosed widespread disease and unexpected findings of bone and salivary gland involvement.

  18. Process for the production of /sup 18/F-2-deoxy-2-fluoro-D-glucose

    SciTech Connect

    Elmaleh, D.R.; Levy, S.; Shiue, C.Y.; Wolf, A.P.

    1986-10-14

    A process is described for the production of /sup 18/F-2-deoxy-2-fluoro-D-glucose which comprises the steps of: (a) producing a compound; (b) reacting the resulting compound with a fluorinating agent in an inert organic solvent with heating at 100/sup 0/C. to 150/sup 0/C; and (c) hydrolyzing the resulting compounds to remove alkyl groups with BBr/sub 3/, BC1/sub 3/ or concentrated hydrochloric acid.

  19. Convergent synthesis and evaluation of (18)F-labeled azulenic COX2 probes for cancer imaging.

    PubMed

    Nolting, Donald D; Nickels, Michael; Tantawy, Mohammed N; Yu, James Y H; Xie, Jingping; Peterson, Todd E; Crews, Brenda C; Marnett, Larry; Gore, John C; Pham, Wellington

    2012-01-01

    The overall objectives of this research are to (i) develop azulene-based positron emission tomography (PET) probes and (ii) image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel (18)F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8 + 2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional (18)F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an (18)F labeling strategy that employed a much milder phosphate buffer. The (18)F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging

  20. Convergent synthesis and evaluation of 18F-labeled azulenic COX2 probes for cancer imaging

    PubMed Central

    Nolting, Donald D.; Nickels, Michael; Tantawy, Mohammed N.; Yu, James Y. H.; Xie, Jingping; Peterson, Todd E.; Crews, Brenda C.; Marnett, Larry; Gore, John C.; Pham, Wellington

    2013-01-01

    The overall objectives of this research are to (i) develop azulene-based positron emission tomography (PET) probes and (ii) image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel 18F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8 + 2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional 18F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an 18F labeling strategy that employed a much milder phosphate buffer. The 18F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging and

  1. Theoretical cross section calculations of medical 13N and 18F radioisotope using alpha induced reaction

    NASA Astrophysics Data System (ADS)

    Kılınç, F.; Karpuz, N.; ćetin, B.

    2017-02-01

    In medical physics, radionuclides are needed to diagnose functional disorders of organs and to diagnose and treat many diseases. Nuclear reactions are significant for the productions of radionuclides. It is important to analyze the cross sections for much different energy. In this study, reactional cross sections calculations on 13N, 18F radioisotopes are with TALYS 1.6 nuclear reaction simulation code. Cross sections calculated and experimental data taken from EXFOR library were compared

  2. Combined use of 18F-FDG and 18F-FMISO in unresectable non-small cell lung cancer patients planned for radiotherapy: a dynamic PET/CT study

    PubMed Central

    Sachpekidis, Christos; Thieke, Christian; Askoxylakis, Vasileios; Nicolay, Nils H; Huber, Peter E; Thomas, Michael; Dimitrakopoulou, Georgia; Debus, Juergen; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

    2015-01-01

    Aim of this study was to evaluate and compare, by means of dynamic and static PET/CT, the distribution patterns and pharmacokinetics of fluorine-18 fluorodeoxyglucose (18F-FDG) and of fluorine-18-fluoromisonidazole (18F-FMISO) in non-small cell lung cancer (NSCLC) patients scheduled for intensity modulated radiation therapy (IMRT). Thirteen patients suffering from inoperable stage III NSCLC underwent PET/CTs with 18F-FDG and 18F-FMISO for tumor metabolism and hypoxia assessment accordingly. Evaluation of PET/CT studies was based on visual analysis, semi-quantitative (SUV) calculations and absolute quantitative estimations, after application of a two-tissue compartment model and a non-compartmental approach. 18F-FDG PET/CT revealed all thirteen primary lung tumors as sites of increased 18F-FDG uptake. Six patients demonstrated also in total 43 18F-FDG avid metastases; these patients were excluded from radiotherapy. 18F-MISO PET/CT demonstrated 12/13 primary lung tumors with faint tracer uptake. Only one tumor was clearly 18F-FMISO avid, (SUVaverage = 3.4, SUVmax = 5.0). Mean values for 18F-FDG, as derived from dPET/CT data, were SUVaverage = 8.9, SUVmax = 15.1, K1 = 0.23, k2 = 0.53, k3 = 0.17, k4 = 0.02, influx = 0.05 and fractal dimension (FD) = 1.25 for the primary tumors. The respective values for 18F-FMISO were SUVaverage = 1.4, SUVmax = 2.2, K1 = 0.26, k2 = 0.56, k3 = 0.06, k4 = 0.06, influx = 0.02 and FD = 1.14. No statistically significant correlation was observed between the two tracers. 18F-FDG PET/CT changed therapy management in six patients, by excluding them from planned IMRT. 18F-FMISO PET/CT revealed absence of significant tracer uptake in the majority of the 18F-FDG avid NSCLCs. Lack of correlation between the two tracers’ kinetics indicates that they reflect different molecular mechanisms and implies the discordance between increased glycolysis and hypoxia in the malignancy. PMID:25973334

  3. In situ observation of fluoride-ion-induced hydroxyapatite collagen detachment on bone fracture surfaces by atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Kindt, J. H.; Thurner, P. J.; Lauer, M. E.; Bosma, B. L.; Schitter, G.; Fantner, G. E.; Izumi, M.; Weaver, J. C.; Morse, D. E.; Hansma, P. K.

    2007-04-01

    The topography of freshly fractured bovine and human bone surfaces was determined by the use of atomic force microscopy (AFM). Fracture surfaces from both kinds of samples exhibited complex landscapes formed by hydroxyapatite mineral platelets with lateral dimensions ranging from ~90 nm × 60 nm to ~20 nm × 20 nm. Novel AFM techniques were used to study these fracture surfaces during various chemical treatments. Significant topographical changes were observed following exposure to aqueous solutions of ethylenediaminetetraacetic acid (EDTA) or highly concentrated sodium fluoride (NaF). Both treatments resulted in the apparent loss of the hydroxyapatite mineral platelets on a timescale of a few seconds. Collagen fibrils situated beneath the overlying mineral platelets were clearly exposed and could be resolved with high spatial resolution in the acquired AFM images. Time-dependent mass loss experiments revealed that the applied agents (NaF or EDTA) had very different resulting effects. Despite the fact that the two treatments exhibited nearly identical results following examination by AFM, bulk bone samples treated with EDTA exhibited a ~70% mass loss after 72 h, whereas for the NaF-treated samples, the mass loss was only of the order of ~10%. These results support those obtained from previous mechanical testing experiments, suggesting that enhanced formation of superficial fluoroapatite dramatically weakens the protein-hydroxyapatite interfaces. Additionally, we discovered that treatment with aqueous solutions of NaF resulted in the effective extraction of noncollagenous proteins from bone powder.

  4. Tailored Near-Infrared Photoemission in Fluoride Perovskites through Activator Aggregation and Super-Exchange between Divalent Manganese Ions.

    PubMed

    Song, Enhai; Ye, Shi; Liu, Tianhui; Du, Peipei; Si, Rui; Jing, Xiping; Ding, Sha; Peng, Mingying; Zhang, Qinyuan; Wondraczek, Lothar

    2015-07-01

    Biomedical imaging and labeling through luminescence microscopy requires materials that are active in the near-infrared spectral range, i.e., within the transparency window of biological tissue. For this purpose, tailoring of Mn(2+)-Mn(2+) activator aggregation is demonstrated within the ABF3 fluoride perovskites. Such tailoring promotes distinct near-infrared photoluminescence through antiferromagnetic super-exchange across effective dimers. The crossover dopant concentrations for the occurrence of Mn(2+) interaction within the first and second coordination shells comply well with experimental observations of concentration quenching of photoluminescence from isolated Mn(2+) and from Mn(2+)-Mn(2+) effective dimers, respectively. Tailoring of this procedure is achieved via adjusting the Mn-F-Mn angle and the Mn-F distance through substitution of the A(+) and/or the B(2+) species in the ABF3 compound. Computational simulation and X-ray absorption spectroscopy are employed to confirm this. The principle is applied to produce pure anti-Stokes near-infrared emission within the spectral range of ≈760-830 nm from codoped ABF3:Yb(3+),Mn(2+) upon excitation with a 976 nm laser diode, challenging the classical viewpoint where Mn(2+) is used only for visible photoluminescence: in the present case, intense and tunable near-infrared emission is generated. This approach is highly promising for future applications in biomedical imaging and labeling.

  5. 18F-FDG PET/CT in Neurolymphomatosis: Report of 3 Cases

    PubMed Central

    Canh, Nguyen Xuan; Tan, Ngo Van; Tung, Tran Thanh; Son, Nguyen Truong; Maurea, Simone

    2014-01-01

    Neurolymphomatosis is a rare manifestation of non-Hodgkin lymphoma characterized by infiltration of peripheral nerves, nerve roots, plexus and cranial nerves by malignant lymphocytes. This report presents positron emission tomography/computed tomography (PET/CT)imaging with 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG) in 3 cases of non-Hodgkin lymphoma with nerve infiltration, including one newly diagnosed lymphoma, one recurrent lymphoma in previous nerve lesions and one newly recurrent lymphoma. PET/CT could reveal the affected neural structures including cranial nerves, spinal nerve roots, brachial plexus, cervicothoracic ganglion, intercostal nerves, branches of the vagus nerve, lumbosacral plexus and sciatic nerves. There was relative concordance between PET/CT and MRI in detection of affected cranial nerves. PET/CT seemed to be better than MRI in detection of affected peripheral nerves. 18F-FDG PET/CT was a whole-body imaging technique with the ability to reveal the affected cranial nerves, peripheral nerves, nerve roots and plexus in non-Hodgkin lymphoma. A thorough understanding of disease and use of advanced imaging modalities will increasingly detect neurolymphomatosis. PMID:27408859

  6. Standardisation of 18F by a coincidence method using full solid angle detectors.

    PubMed

    Nedjadi, Youcef; Bailat, Claude; Caffari, Yvan; Bochud, François

    2010-01-01

    A solution of (18)F was standardised with a 4pibeta-4pigamma coincidence counting system in which the beta detector is a one-inch diameter cylindrical UPS89 plastic scintillator, positioned at the bottom of a well-type 5''x5'' NaI(Tl) gamma-ray detector. Almost full detection efficiency-which was varied downwards electronically-was achieved in the beta-channel. Aliquots of this (18)F solution were also measured using 4pigamma NaI(Tl) integral counting and Monte Carlo calculated efficiencies as well as the CIEMAT-NIST method. Secondary measurements of the same solution were also performed with an IG11 ionisation chamber whose equivalent activity is traceable to the Système International de Référence through the contribution IRA-METAS made to it in 2001; IRA's degree of equivalence was found to be close to the key comparison reference value (KCRV). The (18)F activity predicted by this coincidence system agrees closely with the ionisation chamber measurement and is compatible within one standard deviation of the other primary measurements. This work demonstrates that our new coincidence system can standardise short-lived radionuclides used in nuclear medicine.

  7. [18F]fluorodopa PET shows striatal dopaminergic dysfunction in juvenile neuronal ceroid lipofuscinosis.

    PubMed Central

    Ruottinen, H M; Rinne, J O; Haaparanta, M; Solin, O; Bergman, J; Oikonen, V J; Järvelä, I; Santavuori, P

    1997-01-01

    OBJECTIVES: To investigate whether nigrostriatal dopaminergic hypofunction is related to the extrapyramidal symptoms in patients with juvenile neuronal ceroid lipofuscinosis (JNCL). METHODS: Nine patients with JNCL and seven healthy controls were studied using [18F]fluorodopa PET. RESULTS: In the patients with JNCL [18F]fluorodopa uptake (K[i][occ]) in the putamen was 60% of the control mean and the corresponding figure in the caudate nucleus was 79%. There was a weak correlation between putamen K(i)(occ) values and extrapyramidal symptoms of the patients evaluated by the motor part of the unified Parkinson's disease rating scale (r = -0.57, P < 0.05). The overall severity of the disease also displayed a negative correlation with the K(i)(occ) values in the putamen (r = -0.71, P < 0.05). CONCLUSION: In patients with JNCL there was reduced striatal [18F]fluorodopa uptake, which had a modest correlation with extrapyramidal symptoms. Dysfunction of nigrostriatal dopaminergic neurons is therefore not the only cause of the patients' extrapyramidal symptoms, but degenerative changes in other brain areas are also contributory. Images PMID:9219750

  8. Monitoring Tumor Hypoxia Using 18F-FMISO PET and Pharmacokinetics Modeling after Photodynamic Therapy

    PubMed Central

    Tong, Xiao; Srivatsan, Avinash; Jacobson, Orit; Wang, Yu; Wang, Zhantong; Yang, Xiangyu; Niu, Gang; Kiesewetter, Dale O.; Zheng, Hairong; Chen, Xiaoyuan

    2016-01-01

    Photodynamic therapy (PDT) is an efficacious treatment for some types of cancers. However, PDT-induced tumor hypoxia as a result of oxygen consumption and vascular damage can reduce the efficacy of this therapy. Measuring and monitoring intrinsic and PDT-induced tumor hypoxia in vivo during PDT is of high interest for prognostic and treatment evaluation. In the present study, static and dynamic 18F-FMISO PET were performed with mice bearing either U87MG or MDA-MB-435 tumor xenografts immediately before and after PDT at different time points. Significant difference in tumor hypoxia in response to PDT over time was found between the U87MG and MDA-MB-435 tumors in both static and dynamic PET. Dynamic PET with pharmacokinetics modeling further monitored the kinetics of 18F-FMISO retention to hypoxic sites after treatment. The Ki and k3 parametric analysis provided information on tumor hypoxia by distinction of the specific tracer retention in hypoxic sites from its non-specific distribution in tumor. Dynamic 18F-FMISO PET with pharmacokinetics modeling, complementary to static PET analysis, provides a potential imaging tool for more detailed and more accurate quantification of tumor hypoxia during PDT. PMID:27546160

  9. The Role of 18F-FDG PET/CT Integrated Imaging in Distinguishing Malignant from Benign Pleural Effusion

    PubMed Central

    Sun, Yajuan; Yu, Hongjuan; Ma, Jingquan

    2016-01-01

    Objective The aim of our study was to evaluate the role of 18F-FDG PET/CT integrated imaging in differentiating malignant from benign pleural effusion. Methods A total of 176 patients with pleural effusion who underwent 18F-FDG PET/CT examination to differentiate malignancy from benignancy were retrospectively researched. The images of CT imaging, 18F-FDG PET imaging and 18F-FDG PET/CT integrated imaging were visually analyzed. The suspected malignant effusion was characterized by the presence of nodular or irregular pleural thickening on CT imaging. Whereas on PET imaging, pleural 18F-FDG uptake higher than mediastinal activity was interpreted as malignant effusion. Images of 18F-FDG PET/CT integrated imaging were interpreted by combining the morphologic feature of pleura on CT imaging with the degree and form of pleural 18F-FDG uptake on PET imaging. Results One hundred and eight patients had malignant effusion, including 86 with pleural metastasis and 22 with pleural mesothelioma, whereas 68 patients had benign effusion. The sensitivities of CT imaging, 18F-FDG PET imaging and 18F-FDG PET/CT integrated imaging in detecting malignant effusion were 75.0%, 91.7% and 93.5%, respectively, which were 69.8%, 91.9% and 93.0% in distinguishing metastatic effusion. The sensitivity of 18F-FDG PET/CT integrated imaging in detecting malignant effusion was higher than that of CT imaging (p = 0.000). For metastatic effusion, 18F-FDG PET imaging had higher sensitivity (p = 0.000) and better diagnostic consistency with 18F-FDG PET/CT integrated imaging compared with CT imaging (Kappa = 0.917 and Kappa = 0.295, respectively). The specificities of CT imaging, 18F-FDG PET imaging and 18F-FDG PET/CT integrated imaging were 94.1%, 63.2% and 92.6% in detecting benign effusion. The specificities of CT imaging and 18F-FDG PET/CT integrated imaging were higher than that of 18F-FDG PET imaging (p = 0.000 and p = 0.000, respectively), and CT imaging had better diagnostic consistency with

  10. Synthesis and evaluation of 18F-fluoroethylated benzothiazole derivatives for in vivo imaging of amyloid plaques in Alzheimer's disease.

    PubMed

    Neumaier, B; Deisenhofer, S; Sommer, C; Solbach, C; Reske, S N; Mottaghy, F

    2010-06-01

    Amyloid aggregates play a major role in the development of Alzheimer's disease. Targeting these aggregates by PET probes enables non-invasively the detection and quantification of amyloid deposit distribution in human brains. Based on benzothiazole core structure a series of amyloid imaging agents were developed. Currently [(11)C]2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole (Pittsburgh Compound-B (PIB) is the most specific and widely used amyloid imaging ligand. But due to the short half life of (11)C, longer lived (18)F-labeled derivatives offer logistic advantages and higher contrast images. In this work, three different [(18)F]fluoroethoxy-substituted benzothiazole derivatives ([(18)F]2-(4'-(methylamino)phenyl)-6-(2-fluoroethoxy)benzothiazole, [(18)F]2-((2'-(2-fluoroethoxy)-4'-amino)phenyl)benzothiazole and [(18)F]2-(3'-((2-fluoroethoxy)-4'-amino)phenyl)benzothiazole) were synthesized via [(18)F]fluoroethylation. The latter two derivatives with fluoroethoxy-substitution on the aromatic amino group showed very low binding affinity for amyloid aggregates. In contrast [(18)F]2-(4'-(methylamino)phenyl)-6-(2-fluoroethoxy)benzothiazole with [(18)F]fluoroethoxy-substitution in 6-position showed excellent amyloid imaging properties with respect to lipophilicity, brain entry and brain clearance in normal SCID mice, amyloid plaque binding affinity and specificity.

  11. Kinetic Modeling of the Tau PET Tracer 18F-AV-1451 in Human Healthy Volunteers and Alzheimer's Disease Subjects.

    PubMed

    Barret, Olivier; Alagille, David; Sanabria, Sandra; Comley, Robert A; Weimer, Robby M; Borroni, Edilio; Mintun, Mark; Seneca, Nicholas; Papin, Caroline; Morley, Thomas; Marek, Ken; Seibyl, John P; Tamagnan, Gilles D; Jennings, Danna

    2016-12-01

    (18)F-AV-1451 is currently the most widely used of several experimental tau PET tracers. The objective of this study was to evaluate (18)F-AV-1451 binding with full kinetic analysis using a metabolite corrected arterial input function, and to compare parameters derived from kinetic analysis with standardized uptake value ratio (SUVR) calculated over different imaging time intervals.

  12. Design, synthesis and evaluation of (18)F-labeled bradykinin B1 receptor-targeting small molecules for PET imaging.

    PubMed

    Zhang, Zhengxing; Kuo, Hsiou-Ting; Lau, Joseph; Jenni, Silvia; Zhang, Chengcheng; Zeisler, Jutta; Bénard, François; Lin, Kuo-Shyan

    2016-08-15

    Two fluorine-18 ((18)F) labeled bradykinin B1 receptor (B1R)-targeting small molecules, (18)F-Z02035 and (18)F-Z02165, were synthesized and evaluated for imaging with positron emission tomography (PET). Z02035 and Z02165 were derived from potent antagonists, and showed high binding affinity (0.93±0.44 and 2.80±0.50nM, respectively) to B1R. (18)F-Z02035 and (18)F-Z02165 were prepared by coupling 2-[(18)F]fluoroethyl tosylate with their respective precursors, and were obtained in 10±5 (n=4) and 22±14% (n=3), respectively, decay-corrected radiochemical yield with >99% radiochemical purity. (18)F-Z02035 and (18)F-Z02165 exhibited moderate lipophilicity (LogD7.4=1.10 and 0.59, respectively), and were stable in mouse plasma. PET imaging and biodistribution studies in mice showed that both tracers enabled visualization of the B1R-positive HEK293T::hB1R tumor xenografts with better contrast than control B1R-negative HEK293T tumors. Our data indicate that small molecule antagonists can be used as pharmacophores for the design of B1R-targeting PET tracers.

  13. 18F-fluorothymidine-pet imaging of glioblastoma multiforme: effects of radiation therapy on radiotracer uptake and molecular biomarker patterns.

    PubMed

    Chandrasekaran, Sanjay; Hollander, Andrew; Xu, Xiangsheng; Benci, Joseph L; Davis, James J; Dorsey, Jay F; Kao, Gary

    2013-01-01

    Introduction. PET imaging is a useful clinical tool for studying tumor progression and treatment effects. Conventional (18)F-FDG-PET imaging is of limited usefulness for imaging Glioblastoma Multiforme (GBM) due to high levels of glucose uptake by normal brain and the resultant signal-to-noise intensity. (18)F-Fluorothymidine (FLT) in contrast has shown promise for imaging GBM, as thymidine is taken up preferentially by proliferating cells. These studies were undertaken to investigate the effectiveness of (18)F-FLT-PET in a GBM mouse model, especially after radiation therapy (RT), and its correlation with useful biomarkers, including proliferation and DNA damage. Methods. Nude/athymic mice with human GBM orthografts were assessed by microPET imaging with (18)F-FDG and (18)F-FLT. Patterns of tumor PET imaging were then compared to immunohistochemistry and immunofluorescence for markers of proliferation (Ki-67), DNA damage and repair (γH2AX), hypoxia (HIF-1α), and angiogenesis (VEGF). Results. We confirmed that (18)F-FLT-PET uptake is limited in healthy mice but enhanced in the intracranial tumors. Our data further demonstrate that (18)F-FLT-PET imaging usefully reflects the inhibition of tumor by RT and correlates with changes in biomarker expression. Conclusions. (18)F-FLT-PET imaging is a promising tumor imaging modality for GBM, including assessing RT effects and biologically relevant biomarkers.

  14. Continuous-Flow Synthesis of N-Succinimidyl 4-[18F]fluorobenzoate Using a Single Microfluidic Chip

    PubMed Central

    Kimura, Hiroyuki; Tomatsu, Kenji; Saiki, Hidekazu; Arimitsu, Kenji; Ono, Masahiro; Kawashima, Hidekazu; Iwata, Ren; Nakanishi, Hiroaki; Ozeki, Eiichi; Kuge, Yuji; Saji, Hideo

    2016-01-01

    In the field of positron emission tomography (PET) radiochemistry, compact microreactors provide reliable and reproducible synthesis methods that reduce the use of expensive precursors for radiolabeling and make effective use of the limited space in a hot cell. To develop more compact microreactors for radiosynthesis of 18F-labeled compounds required for the multistep procedure, we attempted radiosynthesis of N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) via a three-step procedure using a microreactor. We examined individual steps for [18F]SFB using a batch reactor and microreactor and developed a new continuous-flow synthetic method with a single microfluidic chip to achieve rapid and efficient radiosynthesis of [18F]SFB. In the synthesis of [18F]SFB using this continuous-flow method, the three-step reaction was successfully completed within 6.5 min and the radiochemical yield was 64 ± 2% (n = 5). In addition, it was shown that the quality of [18F]SFB synthesized on this method was equal to that synthesized by conventional methods using a batch reactor in the radiolabeling of bovine serum albumin with [18F]SFB. PMID:27410684

  15. [(18)F]FDG Uptake in the Aortic Wall Smooth Muscle of Atherosclerotic Plaques in the Simian Atherosclerosis Model.

    PubMed

    Iwaki, Takayuki; Mizuma, Hiroshi; Hokamura, Kazuya; Onoe, Hirotaka; Umemura, Kazuo

    2016-01-01

    Atherosclerosis is a self-sustaining inflammatory fibroproliferative disease that progresses in discrete stages and involves a number of cell types and effector molecules. Recently, [(18)F]fluoro-2-deoxy-D-glucose- ([(18)F]FDG-) positron emission tomography (PET) has been suggested as a tool to evaluate atherosclerotic plaques by detecting accumulated macrophages associated with inflammation progress. However, at the cellular level, it remains unknown whether only macrophages exhibit high uptake of [(18)F]FDG. To identify the cellular origin of [(18)F]FDG uptake in atherosclerotic plaques, we developed a simian atherosclerosis model and performed PET and ex vivo macro- and micro-autoradiography (ARG). Increased [(18)F]FDG uptake in the aortic wall was observed in high-cholesterol diet-treated monkeys and WHHL rabbits. Macro-ARG of [(18)F]FDG in aortic sections showed that [(18)F]FDG was accumulated in the media and intima in the simian model as similar to that in WHHL rabbits. Combined analysis of micro-ARG with immunohistochemistry in the simian atherosclerosis model revealed that most cellular [(18)F]FDG uptake observed in the media was derived not only from the infiltrated macrophages in atherosclerotic plaques but also from the smooth muscle cells (SMCs) of the aortic wall in atherosclerotic lesions.

  16. [18F]FDG Uptake in the Aortic Wall Smooth Muscle of Atherosclerotic Plaques in the Simian Atherosclerosis Model

    PubMed Central

    Mizuma, Hiroshi; Hokamura, Kazuya; Onoe, Hirotaka; Umemura, Kazuo

    2016-01-01

    Atherosclerosis is a self-sustaining inflammatory fibroproliferative disease that progresses in discrete stages and involves a number of cell types and effector molecules. Recently, [18F]fluoro-2-deoxy-D-glucose- ([18F]FDG-) positron emission tomography (PET) has been suggested as a tool to evaluate atherosclerotic plaques by detecting accumulated macrophages associated with inflammation progress. However, at the cellular level, it remains unknown whether only macrophages exhibit high uptake of [18F]FDG. To identify the cellular origin of [18F]FDG uptake in atherosclerotic plaques, we developed a simian atherosclerosis model and performed PET and ex vivo macro- and micro-autoradiography (ARG). Increased [18F]FDG uptake in the aortic wall was observed in high-cholesterol diet-treated monkeys and WHHL rabbits. Macro-ARG of [18F]FDG in aortic sections showed that [18F]FDG was accumulated in the media and intima in the simian model as similar to that in WHHL rabbits. Combined analysis of micro-ARG with immunohistochemistry in the simian atherosclerosis model revealed that most cellular [18F]FDG uptake observed in the media was derived not only from the infiltrated macrophages in atherosclerotic plaques but also from the smooth muscle cells (SMCs) of the aortic wall in atherosclerotic lesions. PMID:28101514

  17. A new assessment model for tumor heterogeneity analysis with [18]F-FDG PET images.

    PubMed

    Wang, Ping; Xu, Wengui; Sun, Jian; Yang, Chengwen; Wang, Gang; Sa, Yu; Hu, Xin-Hua; Feng, Yuanming

    2016-01-01

    It has been shown that the intratumor heterogeneity can be characterized with quantitative analysis of the [18]F-FDG PET image data. The existing models employ multiple parameters for feature extraction which makes it difficult to implement in clinical settings for the quantitative characterization. This article reports an easy-to-use and differential SUV based model for quantitative assessment of the intratumor heterogeneity from 3D [18]F-FDG PET image data. An H index is defined to assess tumor heterogeneity by summing voxel-wise distribution of differential SUV from the [18]F-FDG PET image data. The summation is weighted by the distance of SUV difference among neighboring voxels from the center of the tumor and can thus yield increased values for tumors with peripheral sub-regions of high SUV that often serves as an indicator of augmented malignancy. Furthermore, the sign of H index is used to differentiate the rate of change for volume averaged SUV from its center to periphery. The new model with the H index has been compared with a widely-used model of gray level co-occurrence matrix (GLCM) for image texture characterization with phantoms of different configurations and the [18]F-FDG PET image data of 6 lung cancer patients to evaluate its effectiveness and feasibility for clinical uses. The comparison of the H index and GLCM parameters with the phantoms demonstrate that the H index can characterize the SUV heterogeneity in all of 6 2D phantoms while only 1 GLCM parameter can do for 1 and fail to differentiate for other 2D phantoms. For the 8 3D phantoms, the H index can clearly differentiate all of them while the 4 GLCM parameters provide complicated patterns in the characterization. Feasibility study with the PET image data from 6 lung cancer patients show that the H index provides an effective single-parameter metric to characterize tumor heterogeneity in terms of the local SUV variation, and it has higher correlation with tumor volume change after

  18. A new assessment model for tumor heterogeneity analysis with [18]F-FDG PET images

    PubMed Central

    Wang, Ping; Xu, Wengui; Sun, Jian; Yang, Chengwen; Wang, Gang; Sa, Yu; Hu, Xin-Hua; Feng, Yuanming

    2016-01-01

    It has been shown that the intratumor heterogeneity can be characterized with quantitative analysis of the [18]F-FDG PET image data. The existing models employ multiple parameters for feature extraction which makes it difficult to implement in clinical settings for the quantitative characterization. This article reports an easy-to-use and differential SUV based model for quantitative assessment of the intratumor heterogeneity from 3D [18]F-FDG PET image data. An H index is defined to assess tumor heterogeneity by summing voxel-wise distribution of differential SUV from the [18]F-FDG PET image data. The summation is weighted by the distance of SUV difference among neighboring voxels from the center of the tumor and can thus yield increased values for tumors with peripheral sub-regions of high SUV that often serves as an indicator of augmented malignancy. Furthermore, the sign of H index is used to differentiate the rate of change for volume averaged SUV from its center to periphery. The new model with the H index has been compared with a widely-used model of gray level co-occurrence matrix (GLCM) for image texture characterization with phantoms of different configurations and the [18]F-FDG PET image data of 6 lung cancer patients to evaluate its effectiveness and feasibility for clinical uses. The comparison of the H index and GLCM parameters with the phantoms demonstrate that the H index can characterize the SUV heterogeneity in all of 6 2D phantoms while only 1 GLCM parameter can do for 1 and fail to differentiate for other 2D phantoms. For the 8 3D phantoms, the H index can clearly differentiate all of them while the 4 GLCM parameters provide complicated patterns in the characterization. Feasibility study with the PET image data from 6 lung cancer patients show that the H index provides an effective single-parameter metric to characterize tumor heterogeneity in terms of the local SUV variation, and it has higher correlation with tumor volume change after

  19. Preclinical radiation dosimetry for the novel SV2A radiotracer [18F]UCB-H

    PubMed Central

    2013-01-01

    Background [18F]UCB-H was developed as a novel radiotracer with a high affinity for synaptic vesicle protein 2A, the binding site for the antiepileptic levetiracetam. The objectives of this study were to evaluate the radiation dosimetry of [18F]UCB-H in a preclinical trial and to determine the maximum injectable dose according to guidelines for human biomedical research. The radiation dosimetry was derived by organ harvesting and dynamic micro positron emission tomography (PET) imaging in mice, and the results of both methods were compared. Methods Twenty-four male C57BL-6 mice were injected with 6.96 ± 0.81 MBq of [18F]UCB-H, and the biodistribution was determined by organ harvesting at 2, 5, 10, 30, 60, and 120 min (n = 4 for each time point). Dynamic microPET imaging was performed on five male C57BL-6 mice after the injection of 9.19 ± 3.40 MBq of [18F]UCB-H. A theoretical dynamic bladder model was applied to simulate urinary excretion. Human radiation dose estimates were derived from animal data using the International Commission on Radiological Protection 103 tissue weighting factors. Results Based on organ harvesting, the urinary bladder wall, liver and brain received the highest radiation dose with a resulting effective dose of 1.88E-02 mSv/MBq. Based on dynamic imaging an effective dose of 1.86E-02 mSv/MBq was calculated, with the urinary bladder wall and liver (brain was not in the imaging field of view) receiving the highest radiation. Conclusions This first preclinical dosimetry study of [18F]UCB-H showed that the tracer meets the standard criteria for radiation exposure in clinical studies. The dose-limiting organ based on US Food and Drug Administration (FDA) and European guidelines was the urinary bladder wall for FDA and the effective dose for Europe with a maximum injectable single dose of approximately 325 MBq was calculated. Although microPET imaging showed significant deviations from organ harvesting, the Pearson’s correlation coefficient

  20. Use of 18F-2-Fluorodeoxyglucose to Label Antibody Fragments for Immuno-Positron Emission Tomography of Pancreatic Cancer

    PubMed Central

    2015-01-01

    We generated 18F-labeled antibody fragments for positron emission tomography (PET) imaging using a sortase-mediated reaction to install a trans-cyclooctene-functionalized short peptide onto proteins of interest, followed by reaction with a tetrazine-labeled-18F-2-deoxyfluoroglucose (FDG). The method is rapid, robust, and site-specific (radiochemical yields > 25%, not decay corrected). The availability of 18F-2-deoxyfluoroglucose avoids the need for more complicated chemistries used to generate carbon–fluorine bonds. We demonstrate the utility of the method by detecting heterotopic pancreatic tumors in mice by PET, using anti-Class II MHC single domain antibodies. We correlate macroscopic PET images with microscopic two-photon visualization of the tumor. Our approach provides easy access to 18F-labeled antibodies and their fragments at a level of molecular specificity that complements conventional 18F-FDG imaging. PMID:26955657

  1. Postinjection L-phenylalanine increases basal ganglia contrast in PET scans of 6-18F-DOPA

    SciTech Connect

    Doudet, D.J.; McLellan, C.A.; Aigner, T.G.; Wyatt, R.; Adams, H.R.; Miyake, H.; Finn, R.T.; Cohen, R.M. )

    1991-07-01

    The sensitivity of 18F-DOPA positron emission tomography for imaging presynaptic dopamine systems is limited by the amount of specific-to-nonspecific accumulation of radioactivity in brain. In rhesus monkeys, we have been able to increase this ratio by taking advantage of the lag time between 18F-DOPA injection and the formation of its main metabolite, the amino acid 18F-fluoromethoxydopa, the entrance of which into brain is responsible for most of the brain's nonspecific radioactivity. By infusing an unlabeled amino acid, L-phenylalanine, starting 15 min after 18F-DOPA administration, we preferentially blocked the accumulation of 18F-fluoromethoxydopa by preventing its entrance into brain through competition at the large neutral amino acid transport system of the blood-brain barrier. This method appears as reliable as the original and more sensitive, as demonstrated by the comparison of normal and MPTP-treated animals under both conditions.

  2. Fully-automated synthesis of 16β-18F-fluoro-5α-dihydrotestosterone (FDHT) on the ELIXYS radiosynthesizer

    PubMed Central

    Lazari, Mark; Lyashchenko, Serge K.; Burnazi, Eva M.; Lewis, Jason S.; van Dam, R. Michael; Murphy, Jennifer M.

    2015-01-01

    Noninvasive in vivo imaging of androgen receptor (AR) levels with positron emission tomography (PET) is becoming the primary tool in prostate cancer detection and staging. Of the potential 18F-labeled PET tracers, 18F-FDHT has clinically shown to be of highest diagnostic value. We demonstrate the first automated synthesis of 18F-FDHT by adapting the conventional manual synthesis onto the fully-automated ELIXYS radiosynthesizer. Clinically-relevant amounts of 18F-FDHT were synthesized on ELIXYS in 90 min with decay-corrected radiochemical yield of 29 ± 5% (n = 7). The specific activity was 4.6 Ci/µmol (170 GBq/µmol) at end of formulation with a starting activity of 1.0 Ci (37 GBq). The formulated 18F-FDHT yielded sufficient activity for multiple patient doses and passed all quality control tests required for routine clinical use. PMID:26046518

  3. Charge carrier accumulation in lithium fluoride thin films due to Li-ion absorption by titania (100) subsurface.

    PubMed

    Li, Chilin; Gu, Lin; Guo, Xiangxin; Samuelis, Dominik; Tang, Kun; Maier, Joachim

    2012-03-14

    The thermodynamically required redistribution of ions at given interfaces is being paid increased attention. The present investigation of the contact LiF/TiO(2) offers a highly worthwhile example, as the redistribution processes can be predicted and verified. It consists in Li ion transfer from LiF into the space charge zones of TiO(2). We not only can measure the resulting increase of lithium vacancy conductivity in LiF, we also observe a transition from n- to p-type conductivity in TiO(2) in consistency with the generalized space charge model.

  4. Therapy response monitoring of the early effects of a new BRAF inhibitor on melanoma xenograft in mice: evaluation of (18) F-FDG-PET and (18) F-FLT-PET.

    PubMed

    Geven, Edwin J W; Evers, Stefan; Nayak, Tapan K; Bergström, Mats; Su, Fei; Gerrits, Danny; Franssen, Gerben M; Boerman, Otto C

    2015-01-01

    Inhibition of the V600E mutated BRAF kinase gene (BRAF(V600E) ) is an important and effective approach to treating melanomas. A new specific small molecule inhibitor of BRAF(V600E) , PLX3603, showed potent melanoma growth-inhibiting characteristics in preclinical studies and is currently under clinical investigation. In this study we investigated the feasibility of (18) F-FDG and (18) F-FLT-PET to monitor the early effects of the BRAF(V600E) inhibitor in mice with melanoma xenografts. SCID/beige mice with subcutaneous (s.c.) A375 melanoma xenografts, expressing BRAF(V600E) , received the BRAF(V600E) inhibitor twice daily orally (0, 25, 50 and 75 mg/kg). At 1, 3 and 7 days after start of therapy, the uptake of (18) F-FDG and (18) F-FLT in the tumor and normal tissues was determined in ex vivo tissue samples. Serial (18) F-FDG and (18) F-FLT-PET scans were acquired of animals at 1 day before and 1, 3 and 7 days after start of treatment with 75 mg/kg BRAF(V600E) inhibitor. A dose-dependent decrease in (18) F-FDG uptake in the A375 tumors was observed by ex vivo biodistribution analysis. Administration of 75 mg/kg BRAF inhibitor for 1, 3 and 7 days resulted in a significantly decreased (18) F-FDG uptake in A375 tumors (41, 35 and 51%, respectively). (18) F-FLT uptake in the A375 tumors was low at baseline and no significant changes in (18) F-FLT uptake were observed at any of the doses administered. These effects were corroborated by serial in vivo (18) F-FDG and (18) F-FLT-PET imaging. These data demonstrate that (18) F-FDG-PET can be used as an imaging biomarker to noninvasively evaluate the early effects of PLX3603.

  5. Ab initio path integral simulations for the fluoride ion-water clusters: competitive nuclear quantum effect between F(-)-water and water-water hydrogen bonds.

    PubMed

    Kawashima, Yukio; Suzuki, Kimichi; Tachikawa, Masanori

    2013-06-20

    Small hydrated fluoride ion complexes, F(-)(H2O)n (n = 1-3), have been studied by ab initio hybrid Monte Carlo (HMC) and ab initio path integral hybrid Monte Carlo (PIHMC) simulations. Because of the quantum effect, our simulation shows that the average hydrogen-bonded F(-)···HO distance in the quantum F(-)(H2O) is shorter than that in the classical one, while the relation inverts at the three water molecular F(-)(H2O)3 cluster. In the case of F(-)(H2O)3, we have found that the nuclear quantum effect enhances the formation of hydrogen bonds between two water molecules. In F(-)(H2O)2 and F(-)(H2O)3, the nuclear quantum effect on two different kinds of hydrogen bonds, F(-)-water and water-water hydrogen bonds, competes against each other. In F(-)(H2O)3, thus, the nuclear quantum effect on the water-water hydrogen bond leads to the elongation of hydrogen-bonded F(-)···HO distance, which we suggest this as the possible origin of the structural inversion from F(-)(H2O) to F(-)(H2O)3.

  6. Highly selective "turn-on" fluorescent sensing of fluoride ion based on a conjugated polymer thin film-Fe(3+) complex.

    PubMed

    Ding, Wanchuan; Xu, Jingkun; Wen, Yangping; Zhang, Jie; Liu, Hongtao; Zhang, Zhouxiang

    2017-05-15

    We designed a new fluorescent conjugated polymer thin film sensor via direct electropolymerization of the corresponding electroactive monomer M onto the surface of ITO electrode, and the thin film-Fe(3+) complex was used for the highly-selective detection of fluoride ion (F(-)) in water environmental samples. The as-obtained thin film could effectively detect Fe(3+) as a selective turn-off fluorescent sensor, and exhibited outstanding reversibility. This film in the presence of Fe(3+) showed a highly selective turn-on response toward F(-) over other anions with a 5-fold enhancement in the fluorescence intensity. F(-) with a relatively wide concentration range from 10 μM to 3 mM could be determined in a rather simple and sensitive manner with a detection limit of 6.78 μM (0.128 ppm). Analytical applicability of the film-Fe(3+) complex for determining the levels of F(-) in environmental water samples has been successfully demonstrated by fluorescent analysis with satisfactory results. This strategy will provide a new approach for the facile design of new molecular sensing devices and practical application in environments.

  7. Sulfonic Acid- and Lithium Sulfonate-Grafted Poly(Vinylidene Fluoride) Electrospun Mats As Ionic Liquid Host for Electrochromic Device and Lithium-Ion Battery.

    PubMed

    Zhou, Rui; Liu, Wanshuang; Leong, Yew Wei; Xu, Jianwei; Lu, Xuehong

    2015-08-05

    Electrospun polymer nanofibrous mats loaded with ionic liquids (ILs) are promising nonvolatile electrolytes with high ionic conductivity. The large cations of ILs are, however, difficult to diffuse into solid electrodes, making them unappealing for application in some electrochemical devices. To address this issue, a new strategy is used to introduce proton conduction into an IL-based electrolyte. Poly(vinylidene fluoride-co-hexafluoropropylene) (P(VDF-HFP)) copolymer is functionalized with sulfonic acid through covalent attachment of taurine. The sulfonic acid-grafted P(VDF-HFP) electrospun mats consist of interconnected nanofibers, leading to remarkable improvement in dimensional stability of the mats. IL-based polymer electrolytes are prepared by immersing the modified mats in 1-butyl-3-methylimidazolium tetrafluoroborate (BMIM(+)BF4(-)). It is found that the SO3(-) groups can have Lewis acid-base interactions with the cations (BMIM(+)) of IL to promote the dissociation of ILs, and provide additional proton conduction, resulting in significantly improved ionic conductivity. Using this novel electrolyte, polyaniline-based electrochromic devices show higher transmittance contrast and faster switching behavior. Furthermore, the sulfonic acid-grafted P(VDF-HFP) electrospun mats can also be lithiated, giving additional lithium ion conduction for the IL-based electrolyte, with which Li/LiCoO2 batteries display enhanced C-rate performance.

  8. NOTE: The use of molecular sieves to simulate hot lesions in 18F-fluorodeoxyglucose—positron emission tomography imaging

    NASA Astrophysics Data System (ADS)

    Matheoud, R.; Secco, C.; Ridone, S.; Inglese, E.; Brambilla, M.

    2008-04-01

    We investigated the use of a kind of zeolite, the Bowie chabazite, to produce radioactive sources of different shapes, dimensions and activity concentrations that can be used for lesion simulation in positron emission tomography (PET) imaging. The 18F-fluorodeoxyglucose (18F-FDG) uptake of a group of 12 zeolites was studied as a function of their weight (120-1520 mg) and of the activity concentration of the 18F-FDG solution (1-37 MBq ml-1), using a multiple linear regression model. The reproducibility, homogeneity and stability over time of the 18F-FDG uptake were assessed. The fit of the regression model is good (r2 = 0.83). This relation allows the production of zeolites of a desired 18F-FDG activity using knowledge of the concentration of the soaking solution and the weight of the zeolite. The reproducibility of the 18F-FDG uptake after heating the zeolites is elevated (CV% = 3.68). The almost complete regeneration of the zeolites allows us to reuse them in successive experiments. The stability of the 18F-FDG uptake on zeolites is far from ideal. When placed in a saline solution the 'activated' zeolites release the 18F-FDG with an effective half-time of 53 min. The sealing of the zeolites in plastic film bags has been demonstrated to be effective in preventing any release of 18F-FDG. These features, together with their variable dimensions and shapes, make them ideal 18F-FDG sources with a fixed target-to-background ratio that can be placed anywhere in a phantom to study lesion detectability in PET imaging.

  9. One-step preparation of [(18)F]FPBM for PET imaging of serotonin transporter (SERT) in the brain.

    PubMed

    Qiao, Hongwen; Zhang, Yan; Wu, Zehui; Zhu, Lin; Choi, Seok Rye; Ploessl, Karl; Kung, Hank F

    2016-08-01

    Serotonin transporters (SERT) in the brain play an important role in normal brain function. Selective serotonin reuptake inhibitors such as fluoxetine, sertraline, paroxetine, escitalopram, etc., specifically target SERT binding in the brain. Development of SERT imaging agents may be useful for studying the function of SERT by in vivo imaging. A one-step preparation of [(18)F]FPBM, 2-(2'-(dimethylamino)methyl)-4'-(3-([(18)F]fluoropropoxy)phenylthio)benzenamine, for positron emission tomography (PET) imaging of SERT binding in the brain was achieved. An active OTs intermediate, 9, was reacted with [(18)F]F(-)/K222 to produce [(18)F]FPBM in one step and in high radiochemical yield. This labeling reaction was evaluated and optimized under different temperatures, bases, solvents, and varying amounts of precursor 9. The radiolabeling reaction led to the desired [(18)F]FPBM in one step and the crude product was purified by HPLC purification to give no-carrier-added [(18)F]FPBM (radiochemical yield, 24-33%, decay corrected; radiochemical purity >99%). PET imaging studies in normal monkeys (n=4) showed fast, pronounced uptakes in the midbrain and thalamus, regions known to be rich in SERT binding sites. A displacement experiment with escitalopram (5mg/kg iv injection at 30min after [(18)F]FPBM injection) showed a rapid and complete reversal of SERT binding, suggesting that binding by [(18)F]FPBM was highly specific and reversible. A one-step radiolabeling method coupled with HPLC purification for preparation of [(18)F]FPBM was developed. Imaging studies suggest that it is feasible to use this method to prepare [(18)F]FPBM for in vivo PET imaging of SERT binding in the brain.

  10. Multicore-shell nanofiber architecture of polyimide/polyvinylidene fluoride blend for thermal and long-term stability of lithium ion battery separator

    PubMed Central

    Park, Sejoon; Son, Chung Woo; Lee, Sungho; Kim, Dong Young; Park, Cheolmin; Eom, Kwang Sup; Fuller, Thomas F.; Joh, Han-Ik; Jo, Seong Mu

    2016-01-01

    Li-ion battery, separator, multicoreshell structure, thermal stability, long-term stability. A nanofibrous membrane with multiple cores of polyimide (PI) in the shell of polyvinylidene fluoride (PVdF) was prepared using a facile one-pot electrospinning technique with a single nozzle. Unique multicore-shell (MCS) structure of the electrospun composite fibers was obtained, which resulted from electrospinning a phase-separated polymer composite solution. Multiple PI core fibrils with high molecular orientation were well-embedded across the cross-section and contributed remarkable thermal stabilities to the MCS membrane. Thus, no outbreaks were found in its dimension and ionic resistance up to 200 and 250 °C, respectively. Moreover, the MCS membrane (at ~200 °C), as a lithium ion battery (LIB) separator, showed superior thermal and electrochemical stabilities compared with a widely used commercial separator (~120 °C). The average capacity decay rate of LIB for 500 cycles was calculated to be approximately 0.030 mAh/g/cycle. This value demonstrated exceptional long-term stability compared with commercial LIBs and with two other types (single core-shell and co-electrospun separators incorporating with functionalized TiO2) of PI/PVdF composite separators. The proper architecture and synergy effects of multiple PI nanofibrils as a thermally stable polymer in the PVdF shell as electrolyte compatible polymers are responsible for the superior thermal performance and long-term stability of the LIB. PMID:27833132

  11. Synthesis of uniform rare earth fluoride (NaMF4) nanotubes by in situ ion exchange from their hydroxide [M(OH)3] parents.

    PubMed

    Zhang, Fan; Zhao, Dongyuan

    2009-01-27

    In this article, we demonstrate the production of uniform hexagonal sodium rare earth fluoride (beta-NaMF(4)) nanotubes through a hydrothermal in situ ion-exchange reaction by using rare earth hydroxides [M(OH)(3)] as a parent. The trivalent rare earth hydroxides were hydrothermally prepared at 120 degrees C and