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Fully-automated radiosynthesis of the amyloid tracer [11C] PiB via direct [11C]CO2 fixation-reduction

Fully-automated radiosynthesis of the amyloid tracer [11C] PiB via direct [11C]CO2 fixation-reduction

Finally, a significantly lower radiochemical yield was observed when DMF was tested as a reaction solvent compared to DMSO (entry 15 vs entry 9, Table 1). In some cases, the presence of N-[ 11 C]-4-tolylformamide ([ 11 C]3) was detected. This is in agreement with the proposed reaction mechanism in which a N- 11 C-formamide would be a pre- cursor for the N- 11 C-methyl amine (Additional file 1: Scheme S1). Thus, when DMF was used as a solvent at 100 °C, ([ 11 C] 3 ) was obtained with an RCY of 26% (entry 15, Table 1), whereas when using MeCN and DMSO as solvents at 80 and 50 °C, [ 11 C] 3 was formed in 8 and 14% of RCY, respectively (entries 1 and 8, Table 1).
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Evaluation of androgen-induced effects on the uptake of [18F]FDG, [11C]choline and [11C]acetate in an androgen-sensitive and androgen-independent prostate cancer xenograft model

Evaluation of androgen-induced effects on the uptake of [18F]FDG, [11C]choline and [11C]acetate in an androgen-sensitive and androgen-independent prostate cancer xenograft model

AD treatment by means of surgical castration or AR antagonist both affect tumour viability, which can be detected by nuclear imaging techniques. However, in order to compare tracer internalisation in AD-treated versus non-treated animals accurately, tracer metabolism should remain as far as possible unaffected by AD. The biodistribution of [ 18 F]FDG and [ 11 C]acetate was studied in control and DES-treated animals [18]. In healthy rats and tumour-bearing mice, AD did not alter tracer clear- ance from the blood. Also, the uptake of both tracers in background tissue compartments such as the liver, muscle and heart was not significantly affected [18]. Therefore, the biodistribution profile of [ 18 F]FDG and [ 11 C]acetate is assumed to remain unchanged after AD. This would mean that tracer clearance should not affect PET imaging. Regarding [ 18 F]FDG PET, these data were further confirmed by Jadvar et al. [28]. In a later study of this group, [ 11 C]choline biodistribution was studied in castrated and non-treated tumour-bearing mice using autoradiography. The authors concluded that AD did not change clearance of [ 11 C]choline [26]. In our present study, we did not observe an altered clearance of [ 18 F] FDG, [ 11 C]choline and [ 11 C]acetate following castration, which supports these previously obtained results.
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Clinical value of fluorine-18α-methyltyrosine PET in patients with gliomas: comparison with fluorine-18 fluorodeoxyglucose PET

Clinical value of fluorine-18α-methyltyrosine PET in patients with gliomas: comparison with fluorine-18 fluorodeoxyglucose PET

Radiolabeled amino acids are well-established tracers for brain tumor imaging with PET. The Response Assess- ment in Neuro-Oncology working group has recently rec- ommended the use of amino acid PET imaging for brain tumor management in addition to magnetic resonance imaging [3, 4]. L-[methyl- 11 C]methionine ( 11 C-MET) is the most widely used amino acid PET imaging tracer for gliomas for the preoperative detection, diagnosis of sub- types and grades, differential diagnosis from radiation ne- crosis, estimation of tumor infiltration, and delineation of the border of tumor removal [5, 6]. Methyl- 11 C-choline, another PET radiotracer, potentially reflects the grade of malignancy [7]. However, the short half-life (20 min) of
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In vivo TSPO and cannabinoid receptor type 2 availability early in post-stroke neuroinflammation in rats: a positron emission tomography study

In vivo TSPO and cannabinoid receptor type 2 availability early in post-stroke neuroinflammation in rats: a positron emission tomography study

We utilized a high-resolution animal PET scanner (SHR- 38000, Hamamatsu Photonics, Japan) under an axial field of view (FOV) of 330 mm, a transaxial FOV of 108 mm, and a transaxial spatial resolution of 2.3 mm in the center. Eight animals were scanned twice a day using PET with [ 11 C](R)PK11195 and [ 11 C]NE40 beginning 24 h after PIT. The interval between the two scans was set to 2 h, and the order of the scans was counterbalanced. The animals were anesthetized using an initial dose of chloral hydrate (400 mg/kg, i.p.) followed by a continuous infusion of chloral hydrate (100 mg/kg/h, i.v.) during the entire im- aging experiment. They were placed in the prone position on a fixation plate and then set within the gantry hole of the PET scanner. After a 15-min transmission scan utilizing an external 68 Ge/ 68 Ga rod source (67 MBq) for attenuation correction, a serial emission scan that lasted for 60 min was performed immediately following each tracer injection of [ 11 C](R)PK11195 or [ 11 C]NE40 at a dose of 48 MBq/kg; tracers were injected intravenously through the cannula that was inserted into the tail vein. The specific activity of each tracer used was above 50 GBq/μmol. No arterial sam- pling was conducted. The PET data were reconstructed using 3D DRAMA (iteration 2, gamma 0.1) with a Gauss filter of 1.0 mm in full width at half maximum (FWHM), yielding a voxel size of 0.65 × 0.65 × 1.0167 mm for the re- constructed image. To obtain the anatomical information, X-CT scans were performed immediately following PET measurement using a ClairvivoCT (Shimadzu Corporation, Kyoto, Japan).
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THE CODE COSTANZA  EUR 2104 e

THE CODE COSTANZA EUR 2104 e

In correspondence of every point ZL of the lattice, the program prints : TR = temperature of the reflector KelYin 11 11 TC = " core 11 C = density of the atoms precursor of delayed neu[r]

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Automated synthesis of [11C]L-glutamine on Synthra HCN plus synthesis module

Automated synthesis of [11C]L-glutamine on Synthra HCN plus synthesis module

of helium and ammonia gases was used. The amount of ammonia used is very critical in obtaining the enantioenrichment in the final product. Racemized product was ob- served if excess ammonia existed at the presence of moisture in the first [ 11 C] nitrile in- sertion step, and low yield of [ 11 C] CsCN was observed if less ammonia was used. Therefore, the reaction mixture was bubbled with helium to remove excess ammonia. Azeotropic drying of the crown ether and base was performed to remove moisture prior to the reaction. The use of unconventional cesium bicarbonate was due to the re- ported method suggesting [ 11 C] CsCN gave the best result (Gleede et al., 2015). The precursor 5 in DMF was added to reaction vessel 1 and heated. After the [ 11 C] nitrile insertion step, the resultant [ 11 C] nitrile intermediate 6 was purified on a semi-preparative HPLC to remove unreacted [ 11 C] CsCN and other potential impur- ities. The intermediate 6 needs to be dried before it is treated with mixture of acids in the second step. Considering the size and geometry of the reaction vessel equipped with the synthesis module, it was observed that using less than 1.5 mL of acetonitrile to elute the intermediate into the second reaction vessel is optimal. Therefore, attempts were made to evaluate the trapping of the intermediate 6 on various solid-phase extrac- tion cartridges with different material and sizes of packing material, such as tC18 vac 3 cc, tC18 light, tC18 plus short, and C18 plus sep-pak. Of the sep-paks used, only the C18 sep-pak plus was able to trap the intermediate 6 efficiently. In order to efficiently elute the intermediate 6 from C18 plus sep-pak, it was observed that at least 1.4 mL of
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Biotechnological Production and Characterization of Sophorolipids from Candida bombicola MTCC 1910

Biotechnological Production and Characterization of Sophorolipids from Candida bombicola MTCC 1910

11.a 11.b 11.c 11.d 11.e 12 13 14 15 Page Title Structures of rhamnolipid Structure of trehalose lipid Structure of lactonized and free acid form of sophorolipids Structure of surfactin [r]

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Phenylketonuria: reduced tyrosine brain influx relates to reduced cerebral protein synthesis

Phenylketonuria: reduced tyrosine brain influx relates to reduced cerebral protein synthesis

In order to acquire reliable measurements, a steady state condition in each patient was required. To obtain such a condition, patients fasted prior to the study and refrained from taking amino acid formula. After an overnight fast, some patients consumed a light breakfast with a very lim- ited amount of Phe, whereas other patients remained fasted. We consider the influence of the light breakfast to be minimal, as we previously showed that such a breakfast does neither affect blood Phe nor blood Tyr concentra- tions [30]. Similarly, one could hypothesize that ceasing amino acid formula intake could have affected blood Phe and Tyr concentrations during the study period. First, in- take of amino acid formula could reduce Phe uptake at the gut-blood barrier, thus reducing blood Phe concentra- tions. Second, formula intake could increase blood Tyr concentrations. Whether these effects would in turn influ- ence 11 C-Tyr fluxes remains to be investigated.
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Potential for imaging the high-affinity state of the 5-HT1B receptor: a comparison of three PET radioligands with differing intrinsic activity

Potential for imaging the high-affinity state of the 5-HT1B receptor: a comparison of three PET radioligands with differing intrinsic activity

C reaction by bombarding a mixture of nitro- gen and hydrogen (10%) gas with a beam (35 μA) of pro- tons (16.7 MeV) generated from a biomedical cyclotron (GE PETtrace; Uppsala, Sweden). At the end of irra- diation, the target gas was transferred to a Tracerlab synthesis module (GE PETtrace, Uppsala, Sweden) where the [ 11 C]methane was trapped by cooling the gas to − 140 °C. After replacing the target gas with helium, the [ 11 C]methane was converted into [ 11 C]methyl iodide during 5 min of recirculation of radioactive gas through an iodine evaporation oven at 70 °C, an iodination oven at 720 °C, and a [ 11 C]methyl iodide trap. The [ 11 C]me- thyl iodide was released by heating the trap to 190 °C and then passed through a heated column of AgOTf to generate [ 11 C]methyl triflate. The [ 11 C]methyl triflate was transferred to a septum-sealed reaction vessel (5 mL) containing N-desmethyl precursor (0.1–0.5 mg) and NaOH (0.5 M, 6 μL) in acetone (400 μL). After 2 min at ambient temperature, the reaction mixture was diluted with water (3 mL) and injected onto a reversed phased ACE C-18 HPLC column (250 × 10 mm; Advanced Chromatography Technologies Ltd.; Aberdeen, UK) using a mobile phase of 60% aqueous HCO 2 NH 4 (0.1 M)
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On the Improvement of Wind Power Predictions Based on Terrain Characteristics and Measurements of the Annual Energy Production

On the Improvement of Wind Power Predictions Based on Terrain Characteristics and Measurements of the Annual Energy Production

Nomenclature a Correlation coefficient see Equation 11 b Correlation coefficient see Equation 11 c Correlation coefficient see Equation 11 d Correlation coefficient see Equation 11 e Cor[r]

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Characterization of hepatic tumors using [11C]metomidate through positron emission tomography: comparison with [11C]acetate

Characterization of hepatic tumors using [11C]metomidate through positron emission tomography: comparison with [11C]acetate

Approximately 30% of FNH lesions showed increased uptake of [ 11 C]ACE, and it was not possible to discrim- inate FNH from HCC based on visual assessment or differences in semi-quantitative analysis. The results of the present study indicate that both tracers detect a vari- able yet low percentage of lesions representing HCC and FNH. No liver metastases of other primary tumors were detected with these tracers. However, due to the limited cases and limited kinds of cancers, i.e., only six liver me- tastases and four metastases of colon cancer, this might not be conclusive. The fact that liver metastases of colo- rectal cancer do not take up lipid PET tracers has already been published [11]. In contrast, should this group be larger, uptake would be expected in metastases from prostate cancers and some others (lung, breast).
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Human biodistribution and radiation dosimetry of the 5-HT2A receptor agonist Cimbi-36 labeled with carbon-11 in two positions

Human biodistribution and radiation dosimetry of the 5-HT2A receptor agonist Cimbi-36 labeled with carbon-11 in two positions

the radiolabeled form of the glucuronide conjugate (M2), leaving only the M1 fraction [15]. Caspar et al. [42] found that the O -demethylation is catalyzed by CYP2C19 (cytochrome P-450 enzyme) and CYP2D6, and the relative contribution to hepatic clearance was estimated to be 69% for CYP2D6, with the remaining clearance attributed to CYP2C19 and CYP3A4 (catalyz- ing N -dealkylation and/or hydroxylation). These CYP isoforms are also found in the small intestines [43], which we hypothesize account for part of the high up- take of 11 C-Cimbi-36 in the proximal small intestine throughout the scan. The other part possibly represent- ing specific binding to 5-HT 2A/2C Rs. 11 C-Cimbi-36 also
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Agonist signalling properties of radiotracers used for imaging of dopamine D2/3 receptors

Agonist signalling properties of radiotracers used for imaging of dopamine D2/3 receptors

mation is not only relevant when the radiopharmaceuti- cals are used to evaluate actions of novel drugs which may show biased agonism but also because β-arrestin-2 itself may be involved in the desensitization of DA re- ceptors and as such in the detection of DA. Literature about biased signalling of currently available agonist PET radiotracers 11 C-NPA and 11 C-PHNO at cloned DA receptors does not exist, and therefore, we tested un- labelled (‘cold’) NPA and PHNO for agonism in both the cAMP and β-arrestin-2 assays.

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Upregulation of cannabinoid receptor type 2, but not TSPO, in senescence-accelerated neuroinflammation in mice: a positron emission tomography study

Upregulation of cannabinoid receptor type 2, but not TSPO, in senescence-accelerated neuroinflammation in mice: a positron emission tomography study

also express CB2 reduces detectable radioactivity. Re- cently, we reported that [ 11 C]NE40 binding is increased in the peri-infarct area of the ipsilateral cortex at 24 h after induction of stroke, but not in the contralateral cortex, using a photothrombotic stroke model [25]. Fol- lowing CB2 activation, uptake of a TSPO tracer is ob- served at the chronic stage, indicating that different inflammatory responses of microglia occur in the acute and chronic states after ischemia [26]. This early activa- tion of CB2 might also be observed in a variety of animal models of neurological disorders such as AD, multiple sclerosis, and amyotrophic lateral sclerosis [27]. How- ever, it is unclear whether CB2 is upregulated in animal models of senescence or early-stage mild cognitive impairment.
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Improved synthesis of SV2A targeting radiotracer [11C]UCB-J

Improved synthesis of SV2A targeting radiotracer [11C]UCB-J

Unlike boronic acids, organotrifluoroborates are stable in crystalline solid form and in aprotic solutions making them attractive as precursor materials for synthesis of PET- tracers (Lennox and Lloyd-Jones 2014). However, as already mentioned trifluoroborates need to be converted to boronic acid derivatives in aqueous or protic media to be acti- vated for transmetalation reactions (Lennox and Lloyd-Jones 2014). While conventional catalysis reactions with organotrifluoroborates can proceed for hours, the short half-life of carbon-11 necessitate very short reaction time of a few minutes and rapid initial for- mation of boronic acid is therefore needed. Boronic acid derivatives have also been used directly as precursors in Suzuki-Miyaura reactions, for example in the synthesis of [ 11 C]M-MTEB (Hamill et al. 2005). However, boronic acids can undergo side reactions under coupling conditions, e.g. oxidation, protodeboronation and palladium catalyzed homocoupling. By hydrolyzing trifluoroborates in situ to form moderate concentrations of active species, the reaction can be directed towards the Suzuki-Miyaura coupling re- action more selectively (Lennox and Lloyd-Jones 2014). The hydrolysis rate of trifluoro- borates can be controlled in biphasic solvent system that has slightly basic organic phase and very basic aqueous phase. (Lennox and Lloyd-Jones 2014) Besides DMF- water solvent systems, hydrolysis can also occur in more homogenous solvent mixtures such as THF and water in a 10:1 ratio in the presence of a carbonate salt (Lennox and Lloyd-Jones 2014). THF has also shown to be an excellent solvent for other types of transition metal mediated 11 C-labelling reactions, e.g. carbonylations (Eriksson et al. 2012; Takashima-Hirano et al. 2012; Roslin et al. 2017; Schembri et al. 2019) and Heck reactions (Wang et al. 2015).
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Strategy to develop a MAO-A-resistant 5-hydroxy-l-[β-11C]tryptophan isotopologue based on deuterium kinetic isotope effects

Strategy to develop a MAO-A-resistant 5-hydroxy-l-[β-11C]tryptophan isotopologue based on deuterium kinetic isotope effects

Improved resistance to MAO-A will potentially yield markedly increased intracellular retention of [ 11 C]HTP in neuroendocrine tissues. [ 11 C]HTP is currently used as a universal diagnostic imaging biomarker for benign and malignant NETs [1]. However, a higher amount of intact [ 11 C]HTP in plasma has been shown to improve the tracer uptake in NETs, and patients therefore are pre- medicated with the AADC inhibitor 100 to 200 mg car- bidopa orally 1 h prior to the PET examination [5]. This procedure not only improves sensitivity but also intro- duces a new parameter that directly influences absolute uptake in lesions: the individual time for gastrointestinal absorption of carbiodopa. Additionally, the time from in- gestion of carbidopa until PET examination can be vari- able in case of delays in radiochemistry. This taken together makes direct quantitative comparison between examinations - even repeated scans within an individual - impossible or difficult. Importantly, it precludes the possibility of quantitatively monitoring treatment effi- cacy by using SUVs in individual lesions.
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Measurements of fiducial cross sections for tt¯ production with one or two additional b jets in pp collisions at √s=8 TeV using the ATLAS detector

Measurements of fiducial cross-sections for $$t\bar{t}$$ t t ¯ production with one or two additional b-jets in pp collisions at $$\sqrt{s}$$ s =8 TeV using the ATLAS detector

J. Chudoba 127 , A. J. Chuinard 87 , J. J. Chwastowski 39 , L. Chytka 115 , G. Ciapetti 132a,132b , A. K. Ciftci 4a , D. Cinca 53 , V. Cindro 75 , I. A. Cioara 21 , A. Ciocio 15 , F. Cirotto 104a,104b , Z. H. Citron 172 , M. Ciubancan 26b , A. Clark 49 , B. L. Clark 57 , P. J. Clark 46 , R. N. Clarke 15 , C. Clement 146a,146b , Y. Coadou 85 , M. Cobal 164a,164c , A. Coccaro 49 , J. Cochran 64 , L. Coffey 23 , J. G. Cogan 143 , L. Colasurdo 106 , B. Cole 35 , S. Cole 108 , A. P. Colijn 107 , J. Collot 55 , T. Colombo 58c , G. Compostella 101 , P. Conde Muiño 126a,126b , E. Coniavitis 48 , S. H. Connell 145b , I. A. Connelly 77 , V. Consorti 48 , S. Constantinescu 26b , C. Conta 121a,121b , G. Conti 30 , F. Conventi 104a,j , M. Cooke 15 , B. D. Cooper 78 , A. M. Cooper-Sarkar 120 , T. Cornelissen 175 , M. Corradi 20a , F. Corriveau 87,k , A. Corso-Radu 163 , A. Cortes-Gonzalez 12 , G. Cortiana 101 , G. Costa 91a , M. J. Costa 167 , D. Costanzo 139 , D. Côté 8 , G. Cottin 28 , G. Cowan 77 , B. E. Cox 84 , K. Cranmer 110 , G. Cree 29 , S. Crépé-Renaudin 55 , F. Crescioli 80 , W. A. Cribbs 146a,146b , M. Crispin Ortuzar 120 , M. Cristinziani 21 , V. Croft 106 , G. Crosetti 37a,37b , T. Cuhadar Donszelmann 139 , J. Cummings 176 , M. Curatolo 47 , J. Cúth 83 , C. Cuthbert 150 , H. Czirr 141 , P. Czodrowski 3 , S. D’Auria 53 , M. D’Onofrio 74 , M. J. Da Cunha Sargedas De Sousa 126a,126b , C. Da Via 84 , W. Dabrowski 38a , A. Dafinca 120 , T. Dai 89 , O. Dale 14 , F. Dallaire 95 , C. Dallapiccola 86 , M. Dam 36 , J. R. Dandoy 31 , N. P. Dang 48 , A. C. Daniells 18 , M. Danninger 168 , M. Dano Hoffmann 136 , V. Dao 48 , G. Darbo 50a , S. Darmora 8 , J. Dassoulas 3 , A. Dattagupta 61 , W. Davey 21 , C. David 169 , T. Davidek 129 , E. Davies 120,l , M. Davies 153 , P. Davison 78 , Y. Davygora 58a , E. Dawe 88 , I. Dawson 139 , R. K. Daya-Ishmukhametova 86 , K. De 8 , R. de Asmundis 104a , A. De Benedetti 113 , S. De Castro 20a,20b , S. De Cecco 80 , N. De Groot 106 , P. de Jong 107 , H. De la Torre 82 , F. De Lorenzi 64 , D. De Pedis 132a , A. De Salvo 132a , U. De Sanctis 149 , A. De Santo 149 , J. B. De Vivie De Regie 117 , W. J. Dearnaley 72 , R. Debbe 25 , C. Debenedetti 137 , D. V. Dedovich 65 , I. Deigaard 107 , J. Del Peso 82 , T. Del Prete 124a,124b , D. Delgove 117 , F. Deliot 136 , C. M. Delitzsch 49 , M. Deliyergiyev 75 , A. Dell’Acqua 30 , L. Dell’Asta 22 , M. Dell’Orso 124a,124b , M. Della Pietra 104a,j , D. della Volpe 49 , M. Delmastro 5 , P. A. Delsart 55 , C. Deluca 107 , D. A. DeMarco 158 , S. Demers 176 , M. Demichev 65 , A. Demilly 80 , S. P. Denisov 130 , D. Derendarz 39 , J. E. Derkaoui 135d , F. Derue 80 , P. Dervan 74 , K. Desch 21 , C. Deterre 42 , P. O. Deviveiros 30 , A. Dewhurst 131 , S. Dhaliwal 23 , A. Di Ciaccio 133a,133b , L. Di Ciaccio 5 , A. Di Domenico 132a,132b ,
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Is IP Law Modernization Possible? Assessing Approaches in ACTA, SOPA, and Bill C-11

Is IP Law Modernization Possible? Assessing Approaches in ACTA, SOPA, and Bill C-11

The forum and method of these discussions is just as significant as the requirement for openness. The debates over ACTA and SOPA (and, in a more peripheral way, Bill C-11) show that both governments and copyright holders need to improve their methods of disseminating information. Opponents of ACTA and SOPA were able to reach wide audiences quickly and, most significantly, to mobilize them quickly. Regardless of the merits of their viewpoints, the opponents have arguably the most important factor weighing heavily in their favor: they know how to communicate their message, and they know how to do so persuasively. Opponents (particularly the technology industry) have and will maintain a head start on the government in communication; they control powerful means of dissemination in that they run the major websites. This should encourage copyright holders and the government to talk more directly with them in order to prevent drastic measures like the anti-SOPA blackout.
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Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson's disease

Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson's disease

method of Camsonne et al [36]. Briefly, 1 mg of the pre- cursor (N-sec-butyl-1-(2-chlorophenyl) isoquinoline-3- carboxamide) was dissolved in 500 µL DMSO with 5–10 mg KOH, after trapping the C-11 methyl iodide, the vessel was heated at 80°C for 3 min and purified by HPLC sys- tem comprising a mobile phase pump (Hitachi), an auto- matic sample injector with 5 ml loop (Merck) and a radioactivity detector (in-house construction). Separation was performed on a µ-Bondapak C-18 column (7.8–300 mm, Waters) using methanol and 0.01 M phosphoric acid (700 / 300, v/v) as the mobile phase with a flow of 8 ml/ min. The radioactivity peak with a retention time of 5.6 min, similar to a reference standard was collected. After addition of 50 µL 5 M HCl, the collected fraction was evaporated and the residue was dissolved in saline buffer and sterilized by filtration through a 0.2-µm filter (Millex ® -GV). About 50% of the radioactivity was trapped
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Photolysis and acid cataysed studies of some bifunctional systems

Photolysis and acid cataysed studies of some bifunctional systems

a,S-Epoxyketones have also been observed to undergo isomerisation at the epoxide carbons in a process involving C-C bond cleavage Scheme 11.. Scheme 11 undergoes acetone sensitised geome[r]

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