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Chemoselective pre-conjugate radiohalogenation of unprotected mono- and multimeric peptides via oxime formation

  • Thorsten Poethko , Margret Schottelius , Georgette Thumshirn , Michael Herz , Roland Haubner , Gjermund Henriksen , Horst Kessler , Markus Schwaiger and Hans-Jürgen Wester
Published/Copyright: September 25, 2009
Radiochimica Acta
From the journal Radiochimica Acta Volume 92 Issue 4-6

Abstract

As part of our ongoing efforts in the development of new 18F-labeled peptides for clinical PET imaging, a new two-step 18F-labeling methodology based on the chemoselective oxime formation between an unprotected aminooxy-functionalized peptide and a 18F-labeled aldehyde was investigated and optimized.

4-[18F]Fluorobenzaldehyde ([18F]FB-CHO) was prepared by direct n.c.a. fluorination of 4-formyl-N,N,N-trimethylanilinium triflate and purified by radio-HPLC or a strong-cation-exchange/reverse phase cartridge system. The aminooxyacetic acid (Aoa) modified model peptide LEF-NH2 (Leu-Glu-Phe-NH2) and monomeric, dimeric and tetrameric RGD-containing cyclopeptides were synthesized by solid phase peptide synthesis. Radiochemical yields of N-(4-[18F]fluorobenzylidene)-oxime-formation ([18F]FBOA) with the Aoa-modified unprotected peptides were investigated. Optimized reaction conditions (60 °C, 0.5 mM peptide, 15 min, aqueous solution, pH 2.5) resulted in 70%-90% conjugation yields for all unprotected peptides studied. Chemoselectivity was demonstrated in competition experiments with amino acid mixtures. Biodistribution in M21 melanoma bearing mice showed improved tumor uptake and excretion behaviour in the series c(RGDfE)HEG-Dpr-[18F]FBOA < (c(RGDfE)HEG)2K-Dpr-[18F]FBOA < ((c(RGDfE)HEG)2K)2K-Dpr-[18F]FBOA. Two hours p.i. the fraction of intact c(RGDfE)HEG-K-Dpr-[18F]FBOA in blood, liver, kidney and tumor was >90%, indicating high in vivo stability of the oxime linkage. Initial PET studies with ((c(RGDfE)HEG)2-K)2-K-Dpr-[18F]FBOA showed excellent imaging of M21-melanomas in mice.

In conclusion, the new two-step chemoselective 18F-labeling fulfills all requirements for large scale syntheses of peptides in clinical routine. This methodology is also adaptable to other radioisotopes (e.g. radiohalogenation in general) and will thus offer a broad field of application.

Published Online: 2009-9-25
Published in Print: 2004-4-1

© 2004 Oldenbourg Wissenschaftsverlag GmbH

Articles in the same Issue

  1. Gerhard L. Stöcklin Memorial Issue. Dedication and Appreciation
  2. In Memoriam Gerhard L. Stöcklin
  3. From hot atom chemistry to epithermal chemistry
  4. Excitation functions of deuteron induced nuclear reactions on enriched 78Kr with particular relevance to the production of 76Br
  5. Practical production of 61Cu using natural Co target and its simple purification with a chelating resin for 61Cu-ATSM
  6. Cross section measurements of proton and deuteron induced formation of 103Ag in natural palladium
  7. The Auger-electron emitter 165Er: excitation function of the 165Ho(p,n)165Er process
  8. Cross sections for production of the therapeutic radioisotopes 198Au and 199Au in proton and deuteron induced reactions on 198Pt
  9. Production of 16N for instrument calibration
  10. New determination of the half-life of 205Bi
  11. Some nuclear chemical aspects of medical generator nuclide production at the Los Alamos hot cell facility
  12. A no-carrier-added 72Se/72As radionuclide generator based on distillation
  13. The isolation of 99Mo from fission material for use in the 99Mo/99mTc generator for medical use
  14. 99mTc gel generators based on zirconium molybdate-99Mo: III: Influence of preparatory conditions of zirconium molybdate-99Mo gel on generator performance
  15. Structure of [N,N´-bis(3,5-di-t-butyl-salicylidene)-2-benzyl-1,3-propanediaminato]nitridotechnetium(V) complex, TcN(bzdbsalpn), and nitrido-bridged linear polymeric chains in crystalline syn-isomer
  16. Neutral oxorhenium(V) and oxotechnetium(V) complexes with novel amide thioether dithiolate ligands derived from cysteine
  17. 188Re(V)-DMSA: in-vitro and in-vivo studies on the individual stereo isomers
  18. Analysis of 188Re-EDTMP complexes by HPLC and ultrafiltration
  19. Semi-remote production of Br-76 and preparation of high specific activity radiobrominated pharmaceuticals for PET studies
  20. [123/131I]Iodometomidate as a radioligand for functional diagnosis of adrenal disease: synthesis, structural requirements and biodistribution
  21. Synthesis of [123I]iodine labelled imidazo[1,2-b] pyridazines as potential probes for the study of peripheral benzodiazepine receptors using SPECT
  22. Radioiodination of ammonio-closo-monocarborane, 1-H3N-1-CB11H11. Aspects of labelling chemistry in aqueous solution using Chloramine-T
  23. Chemoselective pre-conjugate radiohalogenation of unprotected mono- and multimeric peptides via oxime formation
  24. A rapid, almost quantitative conversion of [11C]carbon dioxide into [11C]carbon monoxide via [11C]formate and [11C]formyl chloride
  25. Radiosynthesis of (N-[11C]methyl)benperidol for PET investigation of D2 receptor binding
  26. Determination of reaction parameters for the synthesis of the serotonin transporter ligand [11C]DASB: Application to a remotely controlled high yield synthesis
  27. Radiosynthesis and in vitro evaluation of the 5HT2 receptor ligand [N-11C-methyl]-1-[2,5-dimethoxy-4-iodophenyl]-2-methylaminopropane for PET
  28. Synthesis of 4-([18F]fluoromethyl)-2-chlorophenylisothiocyanate: A novel bifunctional 18F-labelling agent
  29. Isotopic tracer studies of chemical behavior of rare earth elements in environmental and biological sciences
  30. A new technique for radiolabelling of humic substances
  31. Trace elements evaluation of some medicinal herbs by instrumental neutron activation analysis
  32. Ultratrace and isotope ratios analyses of some radionuclides by ICP-MS
  33. The study of natural radionuclides and radon exhalation rate in ceramic materials containing fly ash developed in Israel
https://doi.org/10.1524/ract.92.4.317.35591

Articles in the same Issue

  1. Gerhard L. Stöcklin Memorial Issue. Dedication and Appreciation
  2. In Memoriam Gerhard L. Stöcklin
  3. From hot atom chemistry to epithermal chemistry
  4. Excitation functions of deuteron induced nuclear reactions on enriched 78Kr with particular relevance to the production of 76Br
  5. Practical production of 61Cu using natural Co target and its simple purification with a chelating resin for 61Cu-ATSM
  6. Cross section measurements of proton and deuteron induced formation of 103Ag in natural palladium
  7. The Auger-electron emitter 165Er: excitation function of the 165Ho(p,n)165Er process
  8. Cross sections for production of the therapeutic radioisotopes 198Au and 199Au in proton and deuteron induced reactions on 198Pt
  9. Production of 16N for instrument calibration
  10. New determination of the half-life of 205Bi
  11. Some nuclear chemical aspects of medical generator nuclide production at the Los Alamos hot cell facility
  12. A no-carrier-added 72Se/72As radionuclide generator based on distillation
  13. The isolation of 99Mo from fission material for use in the 99Mo/99mTc generator for medical use
  14. 99mTc gel generators based on zirconium molybdate-99Mo: III: Influence of preparatory conditions of zirconium molybdate-99Mo gel on generator performance
  15. Structure of [N,N´-bis(3,5-di-t-butyl-salicylidene)-2-benzyl-1,3-propanediaminato]nitridotechnetium(V) complex, TcN(bzdbsalpn), and nitrido-bridged linear polymeric chains in crystalline syn-isomer
  16. Neutral oxorhenium(V) and oxotechnetium(V) complexes with novel amide thioether dithiolate ligands derived from cysteine
  17. 188Re(V)-DMSA: in-vitro and in-vivo studies on the individual stereo isomers
  18. Analysis of 188Re-EDTMP complexes by HPLC and ultrafiltration
  19. Semi-remote production of Br-76 and preparation of high specific activity radiobrominated pharmaceuticals for PET studies
  20. [123/131I]Iodometomidate as a radioligand for functional diagnosis of adrenal disease: synthesis, structural requirements and biodistribution
  21. Synthesis of [123I]iodine labelled imidazo[1,2-b] pyridazines as potential probes for the study of peripheral benzodiazepine receptors using SPECT
  22. Radioiodination of ammonio-closo-monocarborane, 1-H3N-1-CB11H11. Aspects of labelling chemistry in aqueous solution using Chloramine-T
  23. Chemoselective pre-conjugate radiohalogenation of unprotected mono- and multimeric peptides via oxime formation
  24. A rapid, almost quantitative conversion of [11C]carbon dioxide into [11C]carbon monoxide via [11C]formate and [11C]formyl chloride
  25. Radiosynthesis of (N-[11C]methyl)benperidol for PET investigation of D2 receptor binding
  26. Determination of reaction parameters for the synthesis of the serotonin transporter ligand [11C]DASB: Application to a remotely controlled high yield synthesis
  27. Radiosynthesis and in vitro evaluation of the 5HT2 receptor ligand [N-11C-methyl]-1-[2,5-dimethoxy-4-iodophenyl]-2-methylaminopropane for PET
  28. Synthesis of 4-([18F]fluoromethyl)-2-chlorophenylisothiocyanate: A novel bifunctional 18F-labelling agent
  29. Isotopic tracer studies of chemical behavior of rare earth elements in environmental and biological sciences
  30. A new technique for radiolabelling of humic substances
  31. Trace elements evaluation of some medicinal herbs by instrumental neutron activation analysis
  32. Ultratrace and isotope ratios analyses of some radionuclides by ICP-MS
  33. The study of natural radionuclides and radon exhalation rate in ceramic materials containing fly ash developed in Israel
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