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- Aerts, Joel, et al.
(författare)
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Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules : a European perspective
- 2014
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley-Blackwell. - 0362-4803 .- 1099-1344. ; 57:10, s. 615-620
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Tidskriftsartikel (refereegranskat)abstract
- This document is meant to complement Part B of the EANM Guidelines on current good radiopharmacy practice (cGRPP) in the preparation of radiopharmaceuticals issued by the Radiopharmacy Committee of the European Association of Nuclear Medicine, covering small-scale in-house preparation of radiopharmaceuticals with automated modules. The aim is to provide more detailed and practice-oriented guidance to those who are involved in the small-scale preparation of radiopharmaceuticals, which are not intended for commercial purposes or distribution.
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| 7. |
- Bergman, Sara, et al.
(författare)
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Synthesis and Labelling of a Piperazine-Based Library of 11C-Labeled Ligands for Imaging of the Vesicular Acetylcholine Transporter
- 2014
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 57:8, s. 525-532
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Tidskriftsartikel (refereegranskat)abstract
- The cholinergic system is involved in neurodegenerative diseases, and visualization of cholinergic innervations with positron emission tomography (PET) would be a useful tool in understanding these diseases. A ligand for the vesicular acetylcholine transporter (VAChT), acknowledged as a marker for cholinergic neurons, could serve as such a PET tracer. The aim was to find a VAChT PET tracer using a library concept to create a small but diverse library of labeled compounds. From the same precursor and commercially available aryl iodides 6a-f, six potential VAChT PET tracers, [C-11]-(+/-)5a-f, were C-11-labeled by a palladium (0)-mediated aminocarbonylation, utilizing a standard protocol. The labeled compounds [C-11]-(+/-)5a-f were obtained in radiochemical purities >95% with decay-corrected radiochemical yields and specific radioactivities between 4-25% and 124-597 GBq/mu mol, respectively. Autoradiography studies were then conducted to assess the compounds binding selectivity for VAChT. Labeled compounds [C-11]-(+/-)5d and [C-11]-(+/-)5e showed specific binding but not enough to permit further preclinical studies. To conclude, a general method for a facile synthesis and labeling of a small piperazine-based library of potential PET tracers for imaging of VAChT was shown, and in upcoming work, another scaffold will be explored using this approach.
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| 8. |
- Blom, Elisabeth, et al.
(författare)
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Synthesis and characterization of scVEGF-PEG-[68Ga]NOTA and scVEGF-PEG-[68Ga]DOTA PET tracers
- 2011
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 54:11, s. 685-692
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor (VEGF) signaling via vascular endothelial growth factor receptor 2 (VEGFR-2) on tumor endothelial cells is a critical driver of tumor angiogenesis. Novel anti-angiogenic drugs target VEGF/VEGFR-2 signaling and induce changes in VEGFR-2 prevalence. To monitor VEGFR-2 prevalence in the course of treatment, we are evaluating (68)Ga positron emission tomography imaging agents based on macrocyclic chelators, site-specifically conjugated via polyethylene glycol (PEG) linkers to engineered VEGFR-2 ligand, single-chain (sc) VEGF. The (68)Ga-labeling was performed at room temperature with NOTA (2,2', 2 ''-(1,4,7-triazonane-1,4,7-triyl) triacetic acid) conjugates or at 90 degrees C by using either conventional or microwave heating with NOTA and DOTA (2,2', 2 '', 2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetic acid) conjugates. The fastest (similar to 2min) and the highest incorporation (>90%) of (68)Ga into conjugate that resulted in the highest specific radioactivity (similar to 400MBq/nmol) was obtained with microwave heating of the conjugates. The bioactivity of the NOTA-and DOTA-containing tracers was validated in 3-D tissue culture model of 293/KDR cells engineered to express high levels of VEGFR-2. The NOTA-containing tracer also displayed a rapid accumulation (similar to 20s after intravenous injection) to steady-state level in xenograft tumor models. A combination of high specific radioactivity and maintenance of functional activity suggests that scVEGF-PEG-[(68)Ga] NOTA and scVEGF-PEG-[(68)Ga] DOTA might be promising tracers for monitoring VEGFR-2 prevalence and should be further explored.
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| 9. |
- Blom, Elisabeth, et al.
(författare)
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Synthesis of 18F-labeled biotin analogues
- 2011
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 54:10, s. 681-683
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Tidskriftsartikel (refereegranskat)abstract
- A one-step 18F-labeling strategy was used to prepare three labeled analogues of the vitamin biotin, which can be a useful tracer because of its high affinity for avidin. The labeled compounds were obtained in decay-corrected yields of up to 35%, and specific radioactivity of 320 ± 60 GBq/mmol. When evaluated in situ, the analogues showed good affinity for avidin: 60–75% of the radiolabeled compounds were bound to avidin within 5 min. The binding was site-specific, as shown by blocking experiments with native biotin.
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| 10. |
- Blom, Elisabeth, et al.
(författare)
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Use of perfluoro groups in nucleophilic 18F-fluorination
- 2010
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 53:1, s. 24-30
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Tidskriftsartikel (refereegranskat)abstract
- Substrates with leaving groups that contained perfluoro moieties were investigated in labelling chemistry in order to exploit their properties to improve reactivity and purification. [F-18] (Fluoromethyl) benzene was used as the model target compound. Precursors containing perfluoroalkyl and perfluoroaryl sulfonate moieties were subjected to nucleophilic F-18-fluorination, and the impact of perfluoro groups on the substitution reaction and product purification was investigated. [F-18]Fluoride interacted with perfluoroalkyl chains, precluding nucleophilic substitution. When perfluoroaryl groups were used, the substitution proceeded, and the separation of product was explored. The radiolabelled product was obtained in 32% analytical yield and the radiochemical purity was increased to approximately 77% using fluorous solid phase extraction purification.
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| 18. |
- Eriksson, Jonas, et al.
(författare)
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Transition metal mediated synthesis using [11C]CO at low pressure - a simplified method for 11C-carbonylation
- 2012
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 55, s. 223-228
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Tidskriftsartikel (refereegranskat)abstract
- Transition metal mediated carbonylation with [11C]CO has proven a useful method to label a wide array of compounds in the carbonyl position. However, the general use in radiopharmaceutical synthesis has been hampered by the low solubility of carbon monoxide in most solvents and the resulting challenge to confine [11C]CO in low volume reaction vessels. This paper introduces a method that utilises xenon to transfer pre-concentrated [11C]CO to a sealed disposable glass vial containing carbonylation reagents. The high solubility of xenon in the organic solvent made it possible to confine the [11C]CO without utilising a pressure autoclave or chemical trapping additives. The utility of the method in 11C-carbonylation was investigated by conducting three model reactions, where [11C-carbonyl]N-benzylbenzamide, [11C-carbonyl]triclocarban and [11C-carbonyl]methyl nicotinate were afforded in decay corrected radiochemical yields of 71?+/-?6%, 42?+/-?15% and 29?+/-?10%, respectively. These promising results and the straight forward technical implementation suggest that 11C-cabonylation can become a viable mean to provide labelled carbonyl functionalities in routine radiopharmaceutical synthesis. Compounds labelled with short lived positron emitters are used in Positron Emission Tomography, a molecular imaging technology with applications in clinical diagnostics, clinical research and basic biomedical research.
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| 22. |
- George, Guillaume P. C., et al.
(författare)
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Scavenging strategy for specific activity improvement : application to a new CXCR4-specific cyclopentapeptide positron emission tomography tracer
- 2013
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 56:13, s. 679-685
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Tidskriftsartikel (refereegranskat)abstract
- Huisgen cycloaddition is attractive to label peptide because of its rapidity and bioorthogonality. However, for larger tracers, the physico-chemical differences between the precursor and the tracer are usually insufficient to allow their separation by HPLC, reducing the specific activity. This is of importance for peptidic tracers because the combination of their high-affinity receptor with low specific activity results in the precursor saturating the receptors, causing non-specific tracer binding. Here, we report a fast, one-pot, general strategy to circumvent this issue, yielding a tracer of improved specific activity. It consists in adding a lipophilic azide after the labeling step to scavenge unreacted precursor into a more lipophilic species that does not co-elute with the tracer. We applied this strategy to a new fluorinated cyclopentapeptidic CXCR4 antagonist for the PET imaging of cancer, CCIC15, for which we managed to reduce the apparent peptide concentration by a factor of 34 in 10min. This tracer was radiolabeled by click chemistry with 2-[F-18]fluoroethylazide, yielding the tracer in 18 +/- 6% (n=5) end-of-synthesis radiochemical yields (EOS-RCY) in 1.5h from [F-18]fluoride with a specific activity of 19.4GBq mu mol(-1). Preliminary biological evaluation of the probe confirmed potency and specificity for CXCR4; further biological evaluation is underway.
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| 23. |
- Hall, Håkan, et al.
(författare)
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Pharmacological characterization of 18F-labeled vorozole analogs
- 2012
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 55:14, s. 484-490
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Tidskriftsartikel (refereegranskat)abstract
- Two F-18-labeled analogs of vorozole ([F-18]FVOZ and [F-18]FVOO) have been developed as potential tools for the in vivo characterization of aromatase. The pharmacologicalproperties of these radioligands were evaluated using in vitro binding and in vivo distribution studies in the rat and primate. Saturation binding studies using rat ovary gave K-D and B-max values of 0.21 +/- 0.1 nM and 210 +/- 20 fmol/mg, respectively, for [F-18]FVOZ, and 7.6 +/- 1nMand 293 +/- 12fmol/mg, respectively, for [F-18]FVOO. Organ distribution studies in rats showed the highest accumulation in the adrenal glands, with standardized uptake values (SUVs) of 15 to 20, followed by ovaries and liver with SUVs of approximately 5. Ex vivo and in vitro autoradiography of the rat brain showed specific binding of both [F-18]FVOZ and [F-18]FVOO mainly in the amygdala. Positron emission tomography (PET) studies were performed in the Rhesus monkey, and these showed displaceable binding in the amygdala and the hypothalamus preoptic area. The PET images were also analyzed using masked volume-wise principal component analysis. These studies suggest that [F-18]FVOZ might be a suitable tracer for the study of aromatase in vitro and in vivo, and could be an alternative to [C-11]vorozole in human PET studies.
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| 24. |
- Langstrom, Bengt, et al.
(författare)
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Endogenous compounds labeled with radionuclides of short half-life - some perspectives
- 2013
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 56:3-4, s. 251-262
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Forskningsöversikt (refereegranskat)abstract
- In the article, the strategy and synthesis of some endogenous compounds labeled mainly with 11C are presented. There are some examples illustrating how endogenous labeled compounds in connection with positron emission tomography have unique properties to describe various biological processes, and a few examples of the use of tracers labeled with 13N and 15O are also discussed. Labeled endogenous compounds may be an important asset to describe the conditions and the status of biological systems and might therefore be a key for the future search of individualized medicine.
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| 27. |
- Malmquist, Jonas, et al.
(författare)
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Imaging agent of a TRPA1 inhibitor
- 2013
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 56:9-10, s. 536-537
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Tidskriftsartikel (refereegranskat)abstract
- A method for the preparation of [3'-3H]-4-(2'-chloro-6'- hydroxyphenyl)-2-thioxo-3,4-dihydro-1H-indeno[1,2-d]pyrimidin-5 (2H)-one (1), a TRPA1 inhibitor, was developed for the evaluation of imaging properties of a class of TRPA1 inhibitors. 1 was prepared via tritiation of a protected benzaldehyde followed by a tetrachlorosilane catalyzed multicomponent one-step fusion and was obtained at a specific activity of 0.9 TBq/mmol. A 3H-NMR spectrum on 13.5MBq at 75 μM was recorded.
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| 37. |
- Rahman, Obaidur, et al.
(författare)
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Automated synthesis of F-18-labelled analogs of metomidate, vorozole and harmine using commercial platform
- 2010
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 53:3-4, s. 169-171
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Tidskriftsartikel (refereegranskat)abstract
- Three F-18-labelled PET tracers, 2-[F-18]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate ([F-18]FETO), 6-[(S)-(4-chlorophenyl)-(1H)-1,2,4-triazol-1-yl)methyl]-1-(2-[F-18]fluor oethyl)-1H-benzotriazole ([F-18]FVOZ) and 7-[2-(2-[F-18]fluoroethoxy)ethoxy]-1-9H-beta-carboline ([F-18]FHAR) were synthesized by a one-step nucleophilic fluorination using the automated commercial platform TRACERLab FXFN. The labelled products were obtained with 16-20% isolated decay corrected radiochemical yields after 70-75 min synthesis time. The radiochemical and chemical purities were more than 98% in all cases. The synthesis using commercial platform may make these tracers more accessible for clinical research.
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