The Experts below are selected from a list of 300 Experts worldwide ranked by ideXlab platform
Alan Cuthbertson - One of the best experts on this subject based on the ideXlab platform.
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radiosynthesis and biodistribution of a Prosthetic Group f fenma conjugated to cyclic rgd peptides
Bioconjugate Chemistry, 2010Co-Authors: Dag Erlend Olberg, Alan Cuthbertson, Magne Solbakken, Joseph M Arukwe, Alexandr Kristian, Skjalg Bruheim, Ole Kristian HjelstuenAbstract:We have recently reported a new N-methylaminooxy-based Prosthetic Group for the site-selective introduction of ¹⁸F-fluorine under mild acidic aqueous conditions into model peptides functionalized with a Michael acceptor moiety. To further investigate the utility of this methodology, the radiosynthesis of two cyclic RGD peptides was carried out, and in vivo biodistribution and microPET studies were performed in tumor-bearing mice. A cyclic RGD peptide was functionalized with the Michael acceptors trans-β-nitrostyrene carboxylic acid and 3-vinylsulfonylpropionic acid. Radiolabeling was then performed with the Prosthetic Group O-(2-(2-[¹⁸F]fluoroethoxy)ethyl)-N-methylhydroxylamine (¹⁸F-FENMA) yielding the ¹⁸F-conjugates in moderate yields (8.5-12%). Biodistribution, blocking, and microPET imaging studies were performed in a mouse xenograft model. The vinylsulfonyl-modified conjugate demonstrated good in vitro plasma stability. Biodistribution and microPET studies revealed excellent tumor uptake with low background in key organs and renal elimination as the predominant route of excretion. Blocking studies with coinjected nonlabeled RGD peptide confirmed the in vivo specificity for the integrin α(v)β₃. On the other hand, ¹⁸F-FENMA-nitrostyrene-RGD, although stable at conjugation pH 5, was found to rapidly degrade at physiological pH through loss of the ¹⁸F-Prosthetic Group.
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one step radiosynthesis of 6 18f fluoronicotinic acid 2 3 5 6 tetrafluorophenyl ester 18f f py tfp a new Prosthetic Group for efficient labeling of biomolecules with fluorine 18
Journal of Medicinal Chemistry, 2010Co-Authors: Dag Erlend Olberg, Magne Solbakken, Ole Kristian Hjelstuen, Joseph Arukwe, David Grace, Grete Mork Kindberg, Alan CuthbertsonAbstract:The labeling of biomolecules for positron emission tomography (PET) with no-carrier-added fluorine-18 is almost exclusively accomplished using Prosthetic Groups in a two step procedure. The inherent complexity of the process renders full automation a challenge and leads to protracted synthesis times. Here we describe a new 18F-labeled Prosthetic Group based on nicotinic acid tetrafluorophenyl ester. Reaction of [18F]fluoride at 40 °C with the trimethylammonium precursor afforded 6-[18F]fluoronicotinic acid tetrafluorophenyl ester ([18F]F-Py-TFP) directly in 60−70% yield. [18F]F-Py-TFP was conveniently purified by Sep-Pak cartridge prior to incubation with a peptide containing the RGD sequence. The desired conjugate was formed rapidly and in good yields. An in vitro receptor-binding assay for the integrin αvβ3 was established to explore competition with peptide and peptidomimetic prepared from F-Py-TFP with 125I-echistatin. The nonradioactive conjugates were found to possess high binding affinities with ca...
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a novel Prosthetic Group for site selective labeling of peptides for positron emission tomography
Bioconjugate Chemistry, 2008Co-Authors: Dag Erlend Olberg, Magne Solbakken, Ole Kristian Hjelstuen, Joseph Arukwe, Hege Karlsen, Alan CuthbertsonAbstract:Efficient methodologies for the radiolabeling of peptides with [(18)F]fluoride are a prerequisite to enabling commercialization of peptide-containing radiotracers for positron emission tomography (PET) imaging. It was the purpose of this study to investigate a novel chemoselective ligation reaction comprising conjugation of an [(18)F]-N-methylaminooxy-containing Prosthetic Group to a functionalized peptide. Twelve derivatives of general formula R1-CO-NH-Lys-Gly-Phe-Gly-Lys-OH were synthesized where R1 was selected from a short list of moieties anticipated to be reactive toward the N-methylaminooxy Group. Conjugation reactions were initially carried out with nonradioactive precursors to assess, in a qualitative manner, their general suitability for PET chemistry with only the most promising pairings progressing to full radiochemical assessment. Best results were obtained for the ligation of O-[2-(2-[(18)F]fluoroethoxy)ethyl]-N-methyl-N-hydroxylamine 18 to the maleimidopropionyl-Lys-Gly-Phe-Gly-Lys-OH precursor 10 in acetate buffer (pH 5) after 1 h at 70 degrees C. The non-decay-corrected isolated yield was calculated to be 8.5%. The most encouraging result was observed with the combination 18 and 4-(2-nitrovinyl)benzoyl-Lys-Gly-Phe-Gly-Lys-OH, 9, where the conjugation reaction proceeded rapidly to completion at 30 degrees C after only 5 min. The corresponding non-decay-corrected radiochemical yield for the isolated (18)F-labeled product 27 was 12%. The preliminary results from this study demonstrate the considerable potential of this novel strategy for the radiolabeling of peptides.
Rolf E Swenson - One of the best experts on this subject based on the ideXlab platform.
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rapid synthesis of maleimide functionalized fluorine 18 labeled Prosthetic Group using radio fluorination on the sep pak method
Journal of Labelled Compounds and Radiopharmaceuticals, 2018Co-Authors: Falguni Basuli, Xiang Zhang, Elaine M Jagoda, Peter L Choyke, Rolf E SwensonAbstract:Following our recently published fluorine-18 labeling method, "Radio-fluorination on the Sep-Pak", we have successfully synthesized 6-[18 F]fluoronicotinaldehyde by passing a solution (1:4 acetonitrile: t-butanol) of its quaternary ammonium salt precursor, 6-(N,N,N-trimethylamino)nicotinaldehyde trifluoromethanesulfonate (2), through a fluorine-18 containing anion exchange cartridge (PS-HCO3 ). Over 80% radiochemical conversion was observed using 10 mg of precursor within 1 minute. The [18 F]fluoronicotinaldehyde ([18 F]5) was then conjugated with 1-(6-(aminooxy)hexyl)-1H-pyrrole-2,5-dione to prepare the fluorine-18 labeled maleimide functionalized Prosthetic Group, 6-[18 F]fluoronicotinaldehyde O-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexyl) oxime, 6-[18 F]FPyMHO ([18 F]6). The current Sep-Pak method not only improves the overall radiochemical yield (50 ± 9%, decay-corrected, n = 9) but also significantly reduces the synthesis time (from 60-90 minutes to 30 minutes) when compared with literature methods for the synthesis of similar Prosthetic Groups.
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rapid synthesis of aldehyde and maleimide functionalized fluorine 18 labeled Prosthetic Group using radio fluorination on the sep pak method
The Journal of Nuclear Medicine, 2018Co-Authors: Falguni Basuli, Xiang Zhang, Elaine M Jagoda, Peter L Choyke, Rolf E SwensonAbstract:1062 Objectives: Our objective is to expand the scope of our recently published fluorine-18 labeling method, ‘Radio-fluorination on the Sep-Pak’ for an improved, optimized, simple, reproducible synthesis of fluorine-18 labeled Prosthetic Groups.Methods: Fluorine-18 radiolabeled 6-fluoronicotinaldehyde was prepared quickly by passing the quaternary ammonium triflate precursor through a fluorine-18 trapped Sep-Pak (PS-HCO3) as recently reported by us [1]. The [18F]fluoronicotinaldehyde was then conjugated with 1-(6-(aminooxy)hexyl)-1H-pyrrole-2,5-dione at 80 oC for 5 min to prepare the fluorine-18 labeled maleimide functionalized Prosthetic Group, 6-[18F]fluoronicotinaldehyde O-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexyl) oxime, 6-[18F]FPyMHO. Results: We have successfully prepared 6-[18F]fluoronicotinaldehyde on the Sep-Pak. Fluorination yield of this current method with a shorter synthesis time is comparable to the literature method [2]. The radiochemical yield was 85 ± 3% (uncorrected, n = 6) with a radiochemical purity of >98%. Using 6-[18F]fluoronicotinaldehyde, another useful site specific thiol reactive Prosthetic Group, 6-[18F]FPyMHO, was synthesized. The overall radiochemical yield and purity of 6-[18F]FPyMHO were 44±7% (n = 8, uncorrected) and > 90 % respectively in 30 min synthesis time. Conclusions: The current Sep-Pak method not only improves the overall radiochemical yield of 6-[18F]FPyMHO but also significantly reduces the synthesis time (from 60-90 min to 30 min) when compared with literature methods for the synthesis of similar Prosthetic Groups [3]. This simple and fast radiolabeling procedure at room temperature without azeotropic drying of fluorine-18 has potential applications in the preparation of other useful fluorine-18 labeled synthons. Research Support: This study was funded by the intramural program of the National Institutes of Health. References: [1] Basuli F, Zhang X, Jagoda EM, Choyke PL, and Swenson RE. Nuclear Medicine and Biology, 2016;43:770-772. [2] Kugler F, Ermert J, and Coenen HH. Labeling of benzodioxin piperazines with fluorine-18 as prospective radioligands for selective imaging of dopamine D4 receptors.Journal of Labelled Compounds and Radiopharmaceuticals2013;56:609-618. [3] Moore TM, Akula MR, and Kabalka GW. Fluorine-18 Radiochemistry: A Novel Thiol-Reactive Prosthetic Group, [18F]FBAMPy.Natural Science2016;8:1-7.
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fast indirect fluorine 18 labeling of protein peptide using the useful 6 fluoronicotinic acid 2 3 5 6 tetrafluorophenyl Prosthetic Group a method comparable to direct fluorination
Journal of Labelled Compounds and Radiopharmaceuticals, 2017Co-Authors: Falguni Basuli, Xiang Zhang, Carolyn Woodroofe, Elaine M Jagoda, Peter L Choyke, Rolf E SwensonAbstract:Fluorine-18 labeling of biomolecules is mostly performed by an indirect labeling method using a Prosthetic Group. Fluorine-18 labeled 6-fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester is a useful Prosthetic Group to radiolabel a protein. Recently, we reported an improved preparation of this Prosthetic Group. To test the conjugation efficiency of the labeled ester prepared by this method, we have performed conjugation reactions with a peptide, a protein, and a small molecule. Prostate-specific membrane antigen targeting small molecule [18 F]DCFPyL, αvβ3 integrin receptors targeting peptide [18 F]c(RGDfK) and [18 F]albumin were prepared in good radiochemical yields. The conjugation reactions were completed at 40°C to 50°C in 10 minutes. The overall radiochemical yield was 25% to 43% in 30 to 45 minutes.
Dag Erlend Olberg - One of the best experts on this subject based on the ideXlab platform.
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radiosynthesis and biodistribution of a Prosthetic Group f fenma conjugated to cyclic rgd peptides
Bioconjugate Chemistry, 2010Co-Authors: Dag Erlend Olberg, Alan Cuthbertson, Magne Solbakken, Joseph M Arukwe, Alexandr Kristian, Skjalg Bruheim, Ole Kristian HjelstuenAbstract:We have recently reported a new N-methylaminooxy-based Prosthetic Group for the site-selective introduction of ¹⁸F-fluorine under mild acidic aqueous conditions into model peptides functionalized with a Michael acceptor moiety. To further investigate the utility of this methodology, the radiosynthesis of two cyclic RGD peptides was carried out, and in vivo biodistribution and microPET studies were performed in tumor-bearing mice. A cyclic RGD peptide was functionalized with the Michael acceptors trans-β-nitrostyrene carboxylic acid and 3-vinylsulfonylpropionic acid. Radiolabeling was then performed with the Prosthetic Group O-(2-(2-[¹⁸F]fluoroethoxy)ethyl)-N-methylhydroxylamine (¹⁸F-FENMA) yielding the ¹⁸F-conjugates in moderate yields (8.5-12%). Biodistribution, blocking, and microPET imaging studies were performed in a mouse xenograft model. The vinylsulfonyl-modified conjugate demonstrated good in vitro plasma stability. Biodistribution and microPET studies revealed excellent tumor uptake with low background in key organs and renal elimination as the predominant route of excretion. Blocking studies with coinjected nonlabeled RGD peptide confirmed the in vivo specificity for the integrin α(v)β₃. On the other hand, ¹⁸F-FENMA-nitrostyrene-RGD, although stable at conjugation pH 5, was found to rapidly degrade at physiological pH through loss of the ¹⁸F-Prosthetic Group.
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one step radiosynthesis of 6 18f fluoronicotinic acid 2 3 5 6 tetrafluorophenyl ester 18f f py tfp a new Prosthetic Group for efficient labeling of biomolecules with fluorine 18
Journal of Medicinal Chemistry, 2010Co-Authors: Dag Erlend Olberg, Magne Solbakken, Ole Kristian Hjelstuen, Joseph Arukwe, David Grace, Grete Mork Kindberg, Alan CuthbertsonAbstract:The labeling of biomolecules for positron emission tomography (PET) with no-carrier-added fluorine-18 is almost exclusively accomplished using Prosthetic Groups in a two step procedure. The inherent complexity of the process renders full automation a challenge and leads to protracted synthesis times. Here we describe a new 18F-labeled Prosthetic Group based on nicotinic acid tetrafluorophenyl ester. Reaction of [18F]fluoride at 40 °C with the trimethylammonium precursor afforded 6-[18F]fluoronicotinic acid tetrafluorophenyl ester ([18F]F-Py-TFP) directly in 60−70% yield. [18F]F-Py-TFP was conveniently purified by Sep-Pak cartridge prior to incubation with a peptide containing the RGD sequence. The desired conjugate was formed rapidly and in good yields. An in vitro receptor-binding assay for the integrin αvβ3 was established to explore competition with peptide and peptidomimetic prepared from F-Py-TFP with 125I-echistatin. The nonradioactive conjugates were found to possess high binding affinities with ca...
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a novel Prosthetic Group for site selective labeling of peptides for positron emission tomography
Bioconjugate Chemistry, 2008Co-Authors: Dag Erlend Olberg, Magne Solbakken, Ole Kristian Hjelstuen, Joseph Arukwe, Hege Karlsen, Alan CuthbertsonAbstract:Efficient methodologies for the radiolabeling of peptides with [(18)F]fluoride are a prerequisite to enabling commercialization of peptide-containing radiotracers for positron emission tomography (PET) imaging. It was the purpose of this study to investigate a novel chemoselective ligation reaction comprising conjugation of an [(18)F]-N-methylaminooxy-containing Prosthetic Group to a functionalized peptide. Twelve derivatives of general formula R1-CO-NH-Lys-Gly-Phe-Gly-Lys-OH were synthesized where R1 was selected from a short list of moieties anticipated to be reactive toward the N-methylaminooxy Group. Conjugation reactions were initially carried out with nonradioactive precursors to assess, in a qualitative manner, their general suitability for PET chemistry with only the most promising pairings progressing to full radiochemical assessment. Best results were obtained for the ligation of O-[2-(2-[(18)F]fluoroethoxy)ethyl]-N-methyl-N-hydroxylamine 18 to the maleimidopropionyl-Lys-Gly-Phe-Gly-Lys-OH precursor 10 in acetate buffer (pH 5) after 1 h at 70 degrees C. The non-decay-corrected isolated yield was calculated to be 8.5%. The most encouraging result was observed with the combination 18 and 4-(2-nitrovinyl)benzoyl-Lys-Gly-Phe-Gly-Lys-OH, 9, where the conjugation reaction proceeded rapidly to completion at 30 degrees C after only 5 min. The corresponding non-decay-corrected radiochemical yield for the isolated (18)F-labeled product 27 was 12%. The preliminary results from this study demonstrate the considerable potential of this novel strategy for the radiolabeling of peptides.
Falguni Basuli - One of the best experts on this subject based on the ideXlab platform.
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rapid synthesis of maleimide functionalized fluorine 18 labeled Prosthetic Group using radio fluorination on the sep pak method
Journal of Labelled Compounds and Radiopharmaceuticals, 2018Co-Authors: Falguni Basuli, Xiang Zhang, Elaine M Jagoda, Peter L Choyke, Rolf E SwensonAbstract:Following our recently published fluorine-18 labeling method, "Radio-fluorination on the Sep-Pak", we have successfully synthesized 6-[18 F]fluoronicotinaldehyde by passing a solution (1:4 acetonitrile: t-butanol) of its quaternary ammonium salt precursor, 6-(N,N,N-trimethylamino)nicotinaldehyde trifluoromethanesulfonate (2), through a fluorine-18 containing anion exchange cartridge (PS-HCO3 ). Over 80% radiochemical conversion was observed using 10 mg of precursor within 1 minute. The [18 F]fluoronicotinaldehyde ([18 F]5) was then conjugated with 1-(6-(aminooxy)hexyl)-1H-pyrrole-2,5-dione to prepare the fluorine-18 labeled maleimide functionalized Prosthetic Group, 6-[18 F]fluoronicotinaldehyde O-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexyl) oxime, 6-[18 F]FPyMHO ([18 F]6). The current Sep-Pak method not only improves the overall radiochemical yield (50 ± 9%, decay-corrected, n = 9) but also significantly reduces the synthesis time (from 60-90 minutes to 30 minutes) when compared with literature methods for the synthesis of similar Prosthetic Groups.
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rapid synthesis of aldehyde and maleimide functionalized fluorine 18 labeled Prosthetic Group using radio fluorination on the sep pak method
The Journal of Nuclear Medicine, 2018Co-Authors: Falguni Basuli, Xiang Zhang, Elaine M Jagoda, Peter L Choyke, Rolf E SwensonAbstract:1062 Objectives: Our objective is to expand the scope of our recently published fluorine-18 labeling method, ‘Radio-fluorination on the Sep-Pak’ for an improved, optimized, simple, reproducible synthesis of fluorine-18 labeled Prosthetic Groups.Methods: Fluorine-18 radiolabeled 6-fluoronicotinaldehyde was prepared quickly by passing the quaternary ammonium triflate precursor through a fluorine-18 trapped Sep-Pak (PS-HCO3) as recently reported by us [1]. The [18F]fluoronicotinaldehyde was then conjugated with 1-(6-(aminooxy)hexyl)-1H-pyrrole-2,5-dione at 80 oC for 5 min to prepare the fluorine-18 labeled maleimide functionalized Prosthetic Group, 6-[18F]fluoronicotinaldehyde O-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexyl) oxime, 6-[18F]FPyMHO. Results: We have successfully prepared 6-[18F]fluoronicotinaldehyde on the Sep-Pak. Fluorination yield of this current method with a shorter synthesis time is comparable to the literature method [2]. The radiochemical yield was 85 ± 3% (uncorrected, n = 6) with a radiochemical purity of >98%. Using 6-[18F]fluoronicotinaldehyde, another useful site specific thiol reactive Prosthetic Group, 6-[18F]FPyMHO, was synthesized. The overall radiochemical yield and purity of 6-[18F]FPyMHO were 44±7% (n = 8, uncorrected) and > 90 % respectively in 30 min synthesis time. Conclusions: The current Sep-Pak method not only improves the overall radiochemical yield of 6-[18F]FPyMHO but also significantly reduces the synthesis time (from 60-90 min to 30 min) when compared with literature methods for the synthesis of similar Prosthetic Groups [3]. This simple and fast radiolabeling procedure at room temperature without azeotropic drying of fluorine-18 has potential applications in the preparation of other useful fluorine-18 labeled synthons. Research Support: This study was funded by the intramural program of the National Institutes of Health. References: [1] Basuli F, Zhang X, Jagoda EM, Choyke PL, and Swenson RE. Nuclear Medicine and Biology, 2016;43:770-772. [2] Kugler F, Ermert J, and Coenen HH. Labeling of benzodioxin piperazines with fluorine-18 as prospective radioligands for selective imaging of dopamine D4 receptors.Journal of Labelled Compounds and Radiopharmaceuticals2013;56:609-618. [3] Moore TM, Akula MR, and Kabalka GW. Fluorine-18 Radiochemistry: A Novel Thiol-Reactive Prosthetic Group, [18F]FBAMPy.Natural Science2016;8:1-7.
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fast indirect fluorine 18 labeling of protein peptide using the useful 6 fluoronicotinic acid 2 3 5 6 tetrafluorophenyl Prosthetic Group a method comparable to direct fluorination
Journal of Labelled Compounds and Radiopharmaceuticals, 2017Co-Authors: Falguni Basuli, Xiang Zhang, Carolyn Woodroofe, Elaine M Jagoda, Peter L Choyke, Rolf E SwensonAbstract:Fluorine-18 labeling of biomolecules is mostly performed by an indirect labeling method using a Prosthetic Group. Fluorine-18 labeled 6-fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester is a useful Prosthetic Group to radiolabel a protein. Recently, we reported an improved preparation of this Prosthetic Group. To test the conjugation efficiency of the labeled ester prepared by this method, we have performed conjugation reactions with a peptide, a protein, and a small molecule. Prostate-specific membrane antigen targeting small molecule [18 F]DCFPyL, αvβ3 integrin receptors targeting peptide [18 F]c(RGDfK) and [18 F]albumin were prepared in good radiochemical yields. The conjugation reactions were completed at 40°C to 50°C in 10 minutes. The overall radiochemical yield was 25% to 43% in 30 to 45 minutes.
Magne Solbakken - One of the best experts on this subject based on the ideXlab platform.
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radiosynthesis and biodistribution of a Prosthetic Group f fenma conjugated to cyclic rgd peptides
Bioconjugate Chemistry, 2010Co-Authors: Dag Erlend Olberg, Alan Cuthbertson, Magne Solbakken, Joseph M Arukwe, Alexandr Kristian, Skjalg Bruheim, Ole Kristian HjelstuenAbstract:We have recently reported a new N-methylaminooxy-based Prosthetic Group for the site-selective introduction of ¹⁸F-fluorine under mild acidic aqueous conditions into model peptides functionalized with a Michael acceptor moiety. To further investigate the utility of this methodology, the radiosynthesis of two cyclic RGD peptides was carried out, and in vivo biodistribution and microPET studies were performed in tumor-bearing mice. A cyclic RGD peptide was functionalized with the Michael acceptors trans-β-nitrostyrene carboxylic acid and 3-vinylsulfonylpropionic acid. Radiolabeling was then performed with the Prosthetic Group O-(2-(2-[¹⁸F]fluoroethoxy)ethyl)-N-methylhydroxylamine (¹⁸F-FENMA) yielding the ¹⁸F-conjugates in moderate yields (8.5-12%). Biodistribution, blocking, and microPET imaging studies were performed in a mouse xenograft model. The vinylsulfonyl-modified conjugate demonstrated good in vitro plasma stability. Biodistribution and microPET studies revealed excellent tumor uptake with low background in key organs and renal elimination as the predominant route of excretion. Blocking studies with coinjected nonlabeled RGD peptide confirmed the in vivo specificity for the integrin α(v)β₃. On the other hand, ¹⁸F-FENMA-nitrostyrene-RGD, although stable at conjugation pH 5, was found to rapidly degrade at physiological pH through loss of the ¹⁸F-Prosthetic Group.
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one step radiosynthesis of 6 18f fluoronicotinic acid 2 3 5 6 tetrafluorophenyl ester 18f f py tfp a new Prosthetic Group for efficient labeling of biomolecules with fluorine 18
Journal of Medicinal Chemistry, 2010Co-Authors: Dag Erlend Olberg, Magne Solbakken, Ole Kristian Hjelstuen, Joseph Arukwe, David Grace, Grete Mork Kindberg, Alan CuthbertsonAbstract:The labeling of biomolecules for positron emission tomography (PET) with no-carrier-added fluorine-18 is almost exclusively accomplished using Prosthetic Groups in a two step procedure. The inherent complexity of the process renders full automation a challenge and leads to protracted synthesis times. Here we describe a new 18F-labeled Prosthetic Group based on nicotinic acid tetrafluorophenyl ester. Reaction of [18F]fluoride at 40 °C with the trimethylammonium precursor afforded 6-[18F]fluoronicotinic acid tetrafluorophenyl ester ([18F]F-Py-TFP) directly in 60−70% yield. [18F]F-Py-TFP was conveniently purified by Sep-Pak cartridge prior to incubation with a peptide containing the RGD sequence. The desired conjugate was formed rapidly and in good yields. An in vitro receptor-binding assay for the integrin αvβ3 was established to explore competition with peptide and peptidomimetic prepared from F-Py-TFP with 125I-echistatin. The nonradioactive conjugates were found to possess high binding affinities with ca...
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a novel Prosthetic Group for site selective labeling of peptides for positron emission tomography
Bioconjugate Chemistry, 2008Co-Authors: Dag Erlend Olberg, Magne Solbakken, Ole Kristian Hjelstuen, Joseph Arukwe, Hege Karlsen, Alan CuthbertsonAbstract:Efficient methodologies for the radiolabeling of peptides with [(18)F]fluoride are a prerequisite to enabling commercialization of peptide-containing radiotracers for positron emission tomography (PET) imaging. It was the purpose of this study to investigate a novel chemoselective ligation reaction comprising conjugation of an [(18)F]-N-methylaminooxy-containing Prosthetic Group to a functionalized peptide. Twelve derivatives of general formula R1-CO-NH-Lys-Gly-Phe-Gly-Lys-OH were synthesized where R1 was selected from a short list of moieties anticipated to be reactive toward the N-methylaminooxy Group. Conjugation reactions were initially carried out with nonradioactive precursors to assess, in a qualitative manner, their general suitability for PET chemistry with only the most promising pairings progressing to full radiochemical assessment. Best results were obtained for the ligation of O-[2-(2-[(18)F]fluoroethoxy)ethyl]-N-methyl-N-hydroxylamine 18 to the maleimidopropionyl-Lys-Gly-Phe-Gly-Lys-OH precursor 10 in acetate buffer (pH 5) after 1 h at 70 degrees C. The non-decay-corrected isolated yield was calculated to be 8.5%. The most encouraging result was observed with the combination 18 and 4-(2-nitrovinyl)benzoyl-Lys-Gly-Phe-Gly-Lys-OH, 9, where the conjugation reaction proceeded rapidly to completion at 30 degrees C after only 5 min. The corresponding non-decay-corrected radiochemical yield for the isolated (18)F-labeled product 27 was 12%. The preliminary results from this study demonstrate the considerable potential of this novel strategy for the radiolabeling of peptides.
