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| 5. |
- Barletta, Julien, et al.
(författare)
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Synthesis of [11C-carbonyl]hydroxyureas by a rhodium-mediated carbonylation reaction using [11C]carbon monoxide
- 2006
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 49:5, s. 429-436
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Tidskriftsartikel (refereegranskat)abstract
- [11C]Hydroxyurea has been successfully labelled using [11C]carbon monoxide at low concentration. The decay-corrected radiochemical yield was 38±3%, and the trapping efficiency of [11C]carbon monoxide in the order of 90±5%. This synthesis was performed by a rhodium-mediated carbonylation reaction starting with azidotrimethylsilane and the rhodium complex being made in situ by chloro(1,5-cyclooctadiene)rhodium(I) dimer ([Rh(cod)Cl]2) and 1,2-bis(diphenylphosphino)ethane (dppe). (13C)Hydroxyurea was synthesized using this method and the position of the labelling was confirmed by 13C-NMR. In order to perform accurate LC–MS identification, the derivative 1-hydroxy-3-phenyl[11C]urea was synthesized in a 35±4% decay-corrected radiochemical yield. After 13 µA h bombardment and 21 min synthesis, 1.6 GBq of pure 1-hydroxy-3-phenyl[11C]urea was collected starting from 6.75 GBq of [11C]carbon monoxide and the specific radioactivity of this compound was in the order of 686 GBq/µmol (3.47 nmol total mass). [11C]Hydroxyurea could be used in conjunction with PET to evaluate the uptake of this anticancer agent into tumour tissue in individual patients.
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| 6. |
- Barletta, Julien, et al.
(författare)
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Synthesis of diethyl [carbonyl-C-11]malonate from [C-11]carbon monoxide by rhodium-promoted carbonylation and its application as a reaction intermediate
- 2006
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 49:9, s. 801-809
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Tidskriftsartikel (refereegranskat)abstract
- Rhodium-mediated carbonylation reaction was applied to synthesize diethyl [carbonyl-C-11]malonate using [C-11]carbon monoxide at low concentration. The synthesis was performed starting with ethyl diazoacetate, ethanol and the rhodium complex being made in situ by chloro(1,5-cyclooctadiene)rhodium(l) dimer ([Rh(cod)Cl](2)) and 1,2-bis(diphenylphosphino)ethane (dppe), and the reaction is assumed to proceed via a ketene intermediate. The isolated radiochemical yield was 20% (75% analytical radiochemical yield) and the trapping efficiency of [C-11]carbon monoxide in the order of 85%. The specific radioactivity of this compound was measured at 127 GBq/mu mol (7.28 nmol total mass) after 8 mu Ah bombardment and 35 min synthesis. The corresponding C-13-labelled compound was synthesized using (C-13)carbon monoxide to confirm the position of the carbonyl-labelled atom by C-13-NMR. Diethyl [carbonyl-C-11]malonate was further used in subsequent alkylation step using ethyl iodide and tetrabutylammonium fluoride to obtain diethyl diethyl [carbonyl-C-11]malonate in 50% analytical radiochemical yield.
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| 7. |
- Blom, Elisabeth, et al.
(författare)
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[F-18]/F-19 exchange in fluorine containing compounds for potential use in F-18-labelling strategies
- 2009
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 52:12, s. 504-511
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Tidskriftsartikel (refereegranskat)abstract
- Exchange of [F-18]fluoride with F-19 in various organofluorine compounds in concentrations ranging from 0.06 to 56 mM was explored. We aimed to explore whether exchange reactions can be a potential useful labelling strategy, when there are no requirement of high specific radioactivity. Parameters such as solvents, temperature, conventional vs microwave heating, and the degree of fluorine load in some aromatic and alkyl compounds were investigated with regard to radiochemical yield and specific radioactivity. A series of fluorobenzophenones (1-6), 1-(4-fluorophenyl)ethanone (7), various activated and deactivated fluoro benzenes (8-16), N-(pentafluorophenyl)benzamide (17), (pentafluorophenyl)formamide (18), (tridecafluorohexyl) benzene (19) and tetradecafluorohexane (20) were subjected to [F-18]/F-19 exchange. To test this strategy to label biologically active molecules containing fluorine atoms in an aryl group, two analogues of WAY-100635 (21-22), Lapatinib (23), 2,5,6,7,8-pentafluoro-3-methyinaphthoquinone (24) and 1-(2,4-difluorophenyl)-3-(4-fluorophenyl)propan-l-one (25) were investigated. The multi-fluorinated molecules containing an electron-withdrawing group were successfully labelled at room temperature, whereas the monofluorinated, as well as those containing an electron-donating group, required heating for the exchange reaction to take place.
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| 8. |
- Blom, Elisabeth, 1979-, et al.
(författare)
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Synthesis and in vitro evaluation of 18F-β-carboline alkaloids as PET ligands
- 2008
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 51:6, s. 277-282
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Tidskriftsartikel (refereegranskat)abstract
- A one-step 18F-labelling strategy was used to prepare four 18F-labelled analogues of 7-methoxy-1-methyl-9H-β-carboline (harmine): 7-(2-[18F]fluoroethoxy)-1-methyl-9H-β-carboline (5), 7-(3-[18F]fluoro-propoxy)-1-methyl-9H-β-carboline (6), 7-[2-(2-[18F]fluoroethoxy)ethoxy]-1-methyl-9H-β-carboline (7), and 7-{2-[2-(2-[18F]fluoroethoxy)ethoxy]-ethoxy}-1-methyl-9H-β-carboline (8). These were synthesized as potential PET ligands for monoamine oxidase A. A solution of pure labelled compound in buffer was obtained in < 70 min from end of radionuclide production, with a decay-corrected yield of up to 23%. The average specific binding to MAO-A in rat brain, determined by autoradiography experiments, was highest for compounds 7 and 8 (89 ± 2 and 96 ± 1% respectively), which was obtained at < 1 nM radioligand concentration.
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| 17. |
- Eriksson, Jonas, et al.
(författare)
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[C-11]methyl iodide from [C-11]methane and iodine using a non-thermal plasma method
- 2006
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 49:13, s. 1177-1186
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Tidskriftsartikel (refereegranskat)abstract
- A method and an apparatus for preparing [C-11]methyl iodide from [C-11]methane and iodine in a single pass through a non-thermal plasma reactor has been developed. The plasma was created by applying high voltage (400 V/31 kHz) to electrodes in a stream of helium gas at reduced pressure. The [C-11]methane used in the experiments was produced from [C-11]carbon dioxide via reduction with hydrogen over nickel. [C-11]methyl iodide was obtained with a specific radioactivity of 412 +/- 32 GBq/mu mol within 6 min from approximately 24 GBq of [C-11]carbon dioxide. The decay corrected radiochemical yield was 13 +/- 3% based on [C-11]carbon dioxide at start of synthesis. [C-11]Flumazenil was synthesized via a N-alkylation with the prepared [C-11]methyl iodide.
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| 18. |
- Eriksson, Jonas, et al.
(författare)
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Synthesis of [1-C-11]propyl and [1-C-11]butyl iodide from [C-11]carbon monoxide and their use in alkylation reactions
- 2006
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 49:12, s. 1105-1116
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Tidskriftsartikel (refereegranskat)abstract
- A method to prepare [1-C-11]propyl iodide and [1-C-11]butyl iodide from [C-11]carbon monoxide via a three step reaction sequence is presented. Palladium mediated formylation of ethene with [C-11]carbon monoxide and hydrogen gave [1-C-11]propionaldehyde and [1-C-11]propionic acid. The carbonylation products were reduced and subsequently converted to [1-C-11]propyl iodide. Labelled propyl iodide was obtained in 58 +/- 4% decay corrected radiochemical yield and with a specific radioactivity of 270 +/- 33 GBq/mu mol within 15 min from approximately 12 GBq of [C-11]carbon monoxide. The position of the label was confirmed by C-13-labelling and C-13-NMR analysis. [1-C-11]Butyl iodide was obtained correspondingly from propene and approximately 8 GBq of [C-11]carbon monoxide, in 34 +/- 2% decay corrected radiochemical yield and with a specific radioactivity of 146 +/- 20 GBq/mu mol. The alkyl iodides were used in model reactions to synthesize [O-propyl-1-C-11]propyl and [O-butyl-1-C-11]butyl benzoate. Propyl and butyl analogues of etomidate, a (beta-11-hydroxylase inhibitor, were also synthesized.
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| 19. |
- Erlandsson, Maria, et al.
(författare)
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F-18-labelled vorozole analogues as PET tracer for aromatase.
- 2008
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 51:5, s. 207-212:51, s. 207-212
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Tidskriftsartikel (refereegranskat)abstract
- One- and two-step syntheses for the F-18-labelling of 6-[(S)-(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1-(2-[F-18]fluoroe thyl)-1H-benzotriazole, [F-18]FVOZ, 1 and 6-[(S)-(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1-[2-(2-[18F]fluor oethoxy)ethyl]-1H-benzotriazole, [F-18]FVOO, 2 were developed. In the two-step synthesis, the nucleophilic fluorination step was performed by reacting (S)-6-[(4-chlorophenyl)-(1H-1,2,4-triazol-1-yl)methyl]-1H-benzotriazole (VOZ) with either the F-18-labelled ethane-1,2-diyl bis(4-methylbenzenesulfonate) or the oxydiethane-2,1-diyl bis(4-methylbenzenesulfonate). The radiochemical yields were in the range of 9-13% after the 110-120 min total syntheses and the specific radioactivities were 175 +/- 7 GBq/mu mol and 56 GBq/mu mol for compounds 1 and 2, respectively. In the one-step synthesis, the precursor 2-{6-[(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1H-1,2,3-benzotriaz ol-1-yl}ethyl 4-methylbenzenesulfonate (7) or 1-[2-(2-bromoethoxy)ethyl]-6-[(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)met hyl]-1H-benzotriazole (8) was directly labelled via, an 18F nucleophilic substitution to give the corresponding tracer. The labelled compounds were obtained in 36-99% radioichemical yield after 75-min syntheses. The specific radioactivities are 100 GBq/mu mol for compound 1 and 80 GBq/pmol for compound 2. In vitro autoradiography using frozen rat brains illustrated specific binding in the medial amygdala, the bed nucleus of stria terminalis and the preoptic area, all of which corresponded well to the result of C-11-labelled vorozole.
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| 20. |
- Erlandsson, Maria, 1980-, et al.
(författare)
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Synthesis and in vitro evaluation of 18F-labelled di- and tri(ethylene glycol) metomidate esters
- 2009
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 52:7-8, s. 278-285
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Tidskriftsartikel (refereegranskat)abstract
- By replacing the alkyl chain in a metomidate ester with F-18-labelled di- or tri(ethylene glycol) chains, two F-18-labelled PET tracers, i.e. 2-(2-[F-18]fluoroethoxy)ethyl 1-[(1R)-1-phenylethyll-1 H-imidazole-5-carboxylate (1) and 2-[2-(2-[F-18]fluoroethoxy)-ethoxylethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (2), were synthesized. Two precursors, 2-(2-bromoethoxy)ethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate and 2-[2-(2-chloroethoxy)ethoxylethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate, were prepared and used in one-step nucleophilic [F-18]fluorination reactions using conventional and microwave heating. Organ distribution, frozen section autoradiography and metabolite analysis were performed. The decay-corrected radiochemical yields of 1 and 2 were 26 +/- 8 and 23 +/- 8%, respectively, when they were prepared using conventional heating. By performing microwave heating, the reaction time could be decreased and the yields of analogues 1 and 2 could be increased to 57 +/- 12 and 51 +/- 18%, respectively. Organ distribution studies in the rat showed considerable uptake in the lungs, adrenals and liver. Both compounds bound with low nonspecific binding (1: approx. 20-30%; 2: 2.9% or lower) to tissue from pig and human normal and pathologic adrenals. Metabolite analyses were performed in rats after 5 and 30 min for tracer 1 (20 +/- 6 and 2 +/- 1 %) and tracer 2 (27 +/- 5 and 6 +/- 4%). Both compounds are interesting candidates for the detection of different types of adrenal disorders.
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| 22. |
- Frank, Richard A., et al.
(författare)
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The Imaging Continuum : Bench to Biomarkers to Diagnostics
- 2007
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 50:9-10, s. 746-769
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Forskningsöversikt (refereegranskat)abstract
- Innovation in basic and applied science has brought radiotracers to fruition as diagnostics. Non-invasive, longitudinal, and quantifiable molecular imaging is the key to diagnosing and monitoring numerous illnesses, with more to come from characterization of the clinical relevance of findings from genomics research. Radiotracers enable real-time in vivo studies of the effects of drug candidates on receptors, pathways, pharmacodynamics, and clinically relevant endpoints, thereby providing both early detection of pathophysiology to enable early intervention, and then monitoring of treatment responses to enable individualization of treatment regimens. We review developments which have translated imaging from bench to bedside, or biomarkers to diagnostics. Notable developments include (1) synthesis methods for rapid 11C labeling of biomolecules to high specific radioactivity; (2) ligand-binding assays for screening molecular imaging agents rather than drugs; (3) in vivo imaging of radiotracers in animals; (4) discovering the imaging advantages of 99mTc, 11C, and 18F; (5) co-registration and automated quantitative assessment of high spatial resolution CT and MR images with molecular images from PET for longitudinal studies of treatment effect.
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| 26. |
- Ilovich, Ohad, et al.
(författare)
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Rhodium-mediated [11C]Carbonylation : A library of N-phenyl-N′-{4-(4-quinolyloxy)-phenyl}-[11C]-urea derivatives as potential PET angiogenic probes
- 2009
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 52:5, s. 151-157
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Tidskriftsartikel (refereegranskat)abstract
- As part of our ongoing investigation into the imaging of angiogenic processes, a small library of eight vascular endothelial growth factor receptor-2 (VEGFR-2)/platelet-derived growth factor receptor beta dual inhibitors based on the N-phenyl-N'-4-(4-quinolyloxy)-phenyl-urea was labelled with C-11 (beta(+), t(1/2) = 20.4 min) in the urea carbonyl position via rhodium-mediated carbonylative cross-coupling of an aryl azide and different anilines. The decay-corrected radiochemical yields of the isolated products were in the range of 38-81% calculated from [C-11]carbon monoxide. Starting with 10.7+/-0.5 GBq of [C-11]carbon monoxide, 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-3-(4-fluoro-phenyl)-[C-11]-urea (2.1 GBq) was isolated after total reaction time of 45 min with a specific activity of 92+/-4 GBq mu mol(-1).
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| 27. |
- Karimi, Farhad, et al.
(författare)
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Synthesis of C-11-labelled metomidate analogues as adrenocortical imaging agents.
- 2008
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 51:6, s. 273-276:51, s. 273-276
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Tidskriftsartikel (refereegranskat)abstract
- Clinical findings using [C-11]methyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate ([C-11]MTO, 1) show high uptake in lesions of adrenocortical origin, including adenomas, but low uptake in lesions of non-adrenocortical origin. In this paper the synthesis and preclinical evaluation of two new C-11-labelled analogues of MTO, [C-11]methyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate ([C-11]CLM, 2) and [C-11]methyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate ([C-11]BRM, 3), using frozen-section autoradiography, organ distribution and a metabolic study are presented.
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| 28. |
- Långström, Bengt, et al.
(författare)
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[11C]Carbon monoxide, a versatile and useful precursor in labelling chemistry for PET-ligand development
- 2007
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 50:9-10, s. 794-810
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Forskningsöversikt (refereegranskat)abstract
- In this review the recent progress in the development of suitable precursors for 11C-labelling is discussed. Especially the last few years' advancement of the use of [11C] carbon monoxide as a versatile and useful precursor in labelling chemistry is presented. The development is set in perspective of its potential in applying molecular imaging tools in drug and tracer development.The possibility of exploring small tracer libraries utilizing the microdosing concept is explored.
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| 29. |
- Matsson, Olle, et al.
(författare)
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Isotope effects for fluorine-18 and carbon-11 in the study of reaction mechanism
- 2007
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 50:11-12, s. 982-988
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Forskningsöversikt (refereegranskat)abstract
- The use of kinetic isotope effects (KIEs) for the short-lived radionuclides 11C and 18F in the study of reaction mechanisms is described using some examples. Leaving group fluorine KIEs (k 18/k19) have been utilized to determine the rate-limiting step for nucleophilic aromatic substitution reactions (SNAr). The fluorine KIE was also used to probe the effect of changing solvent and nucleophile steric hindrance on rate-limiting step. The mechanism for a base promoted elimination reaction was determined to be stepwise (E1cB) by a multiple KIE study including the leaving group fluorine KIE. The transition state structures for aliphatic nucleophilic substitution reactions (SN2) have been investigated by multiple KIE studies for cases where the substrate substitution, leaving group or solvent has been varied. Carbon KIEs for labelled α-carbon atom in the substrate are large, k11/k14 = 1.189-1.220. For labelled nucleophile cyanide ion. k11/k 14 = 0.99951-1.0119.
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| 31. |
- Rahman, Obaidur, et al.
(författare)
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Synthesis of N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)[carbonyl-11C]aceta mide ([carbonyl-11C]DAA1106) and analogues using [11C]carbon monoxide and palladium(0) complex
- 2007
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 50:13, s. 1192-1199
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Tidskriftsartikel (refereegranskat)abstract
- N-(2,5-Dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide (DAA1106), a potent and selective ligand for peripheral benzodiazepine receptor, and eight structurally related analogues were labelled with 11C at the carbonyl position using a low concentration of [11C]carbon monoxide and the micro-autoclave technique. A combinatorial approach was applied to synthesize the analogues using similar reaction conditions. Palladium-mediated carbonylation using tetrakis(triphenylphosphine)palladium, various amines and methyl iodide or iodobenzene was employed in the synthesis. The 11C-labelled products were obtained with 10-55% decay-corrected radiochemical yields and the final product was more than 97% pure in all cases. Specific radioactivity was determined for the compound [carbonyl-11C]DAA1106 using a single experiment and a 10-μAh bombardment. The specific radioactivity, measured 36min after end of bombardment, was 455 GBq/μmol. Synthetic routes to the precursors and reference compounds were also developed. The presented approach is a novel method for the synthesis of [carbonyl-11C]DAA1106 and its analogues, and allows the formation of a library of 11C-labelled DAA1106 analogues which can be used to optimize the performance as a potential positron emission tomography tracer.
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| 42. |
- Åberg, Ola, 1978-, et al.
(författare)
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Synthesis and Biological Evaluation of [Carboxyl-11C]eprosartan
- 2009
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 52:8, s. 295-303
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Tidskriftsartikel (refereegranskat)abstract
- Essential hypertension occurs in approximately 25% of the adult population and one cause of hypertension is primary aldosteronism. Targeting the angiotensin II AT1 receptor using PET and an appropriate tracer may offer a diagnostic method for adrenocortical tissue. This report describes the synthesis of the selective AT1 receptor antagonist [carboxyl-11C]eprosartan 10, 4-[2-butyl-5-((E)-2-carboxy-3-thiophen-2-yl-propenyl)-imidazol-1-ylmethyl]-[carboxyl-11C]benzoic acid, and its precursor (E)-3-[2-butyl-3-(4-iodo-benzyl)-3H-imidazol-4-yl]-2-thiophen-2-ylmethyl-acrylic acid 9. 11C-carboxylation of the iodobenzyl moiety was performed using a palladium-mediated reaction with [11C]carbon monoxide in the presence of tetra-n-butyl-ammonium hydroxide in a micro-autoclave using a temperature gradient from 25 to 140°C over 5 min. After purification by semipreparative HPLC, [carboxyl-11C]eprosartan 10 was obtained in 37–54% decay-corrected radiochemical yield (from [11C]carbon monoxide) with a radiochemical purity >95% within 35 min of the end of bombardment (EOB). A 5-µAh bombardment gave 2.04 GBq of 10 (50% rcy from [11C]carbon monoxide) with a specific activity of 160 GBq µmol−1 at 34 min after EOB. Frozen-section autoradiography shows specific binding in kidney, lung and adrenal cortex. In vivo experiments in rats demonstrate a high accumulation in kidney, liver and intestinal wall.
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