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{sup 18}F-Fluoroglucosylation of peptides, exemplified on cyclo(RGDfK)

Abstract

Oxime formation between an aminooxy-functionalized peptide and an {sup 18}F-labelled aldehyde has recently been introduced as a powerful method for the rapid one-step chemoselective synthesis of radiofluorinated peptides. Here, the potential of using routinely produced and thus readily available [{sup 18}F]fluorodeoxyglucose ([{sup 18}F](FDG)) as the aldehydic prosthetic group was investigated using an aminooxyacetyl-conjugated cyclic RGD peptide (cyclo(RGDfK)(Aoa-Boc)) as a model peptide. The use of [{sup 18}F]FDG from routine production ([{sup 18}F]FDGTUM) containing an excess of d-glucose did not allow the radiosynthesis of [{sup 18}F]FDG-RGD in activities >37 MBq in reasonable yield, rendering the direct use of clinical grade [{sup 18}F]FDG for the routine clinical synthesis of {sup 18}F-labelled peptides impossible. Using no-carrier-added (n.c.a.) [{sup 18}F]FDG obtained via HPLC separation of [{sup 18}F]FDGTUM from excess glucose, however, afforded [{sup 18}F]FDG-RGD in yields of 56-93% (decay corrected) and activities up to 37 MBq. Suitable reaction conditions were 20 min at 120 C and pH 2.5, and a peptide concentration of 5 mM. In a preliminary in vivo biodistribution study in M21 melanoma-bearing nude mice, [{sup 18}F]FDG-RGD showed increased tumour accumulation compared to the ''gold standard'' [{sup 18}F]galacto-RGD (2.18 vs 1.49 %iD/g, respectively, at 120 min after injection), but also slightly increased uptake  More>>
Authors:
Hultsch, Christina; Schottelius, Margret; Auernheimer, Joerg; Alke, Andrea; Wester, Hans-Juergen [1] 
  1. Technische Universitaet Muenchen, Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Muenchen (Germany)
Publication Date:
Sep 15, 2009
Product Type:
Journal Article
Resource Relation:
Journal Name: European Journal of Nuclear Medicine and Molecular Imaging; Journal Volume: 36; Journal Issue: 9
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; FLUORINE 18; LABELLED COMPOUNDS; PEPTIDES; PHARMACOLOGY; RADIOPHARMACEUTICALS
OSTI ID:
21226571
Country of Origin:
Germany
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 1619-7070; TRN: DE09FB532
Availability:
Available from: http://dx.doi.org/10.1007/s00259-009-1122-0
Submitting Site:
DEN
Size:
page(s) 1469-1474
Announcement Date:
Nov 05, 2009

Citation Formats

Hultsch, Christina, Schottelius, Margret, Auernheimer, Joerg, Alke, Andrea, and Wester, Hans-Juergen. {sup 18}F-Fluoroglucosylation of peptides, exemplified on cyclo(RGDfK). Germany: N. p., 2009. Web. doi:10.1007/S00259-009-1122-0.
Hultsch, Christina, Schottelius, Margret, Auernheimer, Joerg, Alke, Andrea, & Wester, Hans-Juergen. {sup 18}F-Fluoroglucosylation of peptides, exemplified on cyclo(RGDfK). Germany. doi:10.1007/S00259-009-1122-0.
Hultsch, Christina, Schottelius, Margret, Auernheimer, Joerg, Alke, Andrea, and Wester, Hans-Juergen. 2009. "{sup 18}F-Fluoroglucosylation of peptides, exemplified on cyclo(RGDfK)." Germany. doi:10.1007/S00259-009-1122-0. https://www.osti.gov/servlets/purl/10.1007/S00259-009-1122-0.
@misc{etde_21226571,
title = {{sup 18}F-Fluoroglucosylation of peptides, exemplified on cyclo(RGDfK)}
author = {Hultsch, Christina, Schottelius, Margret, Auernheimer, Joerg, Alke, Andrea, and Wester, Hans-Juergen}
abstractNote = {Oxime formation between an aminooxy-functionalized peptide and an {sup 18}F-labelled aldehyde has recently been introduced as a powerful method for the rapid one-step chemoselective synthesis of radiofluorinated peptides. Here, the potential of using routinely produced and thus readily available [{sup 18}F]fluorodeoxyglucose ([{sup 18}F](FDG)) as the aldehydic prosthetic group was investigated using an aminooxyacetyl-conjugated cyclic RGD peptide (cyclo(RGDfK)(Aoa-Boc)) as a model peptide. The use of [{sup 18}F]FDG from routine production ([{sup 18}F]FDGTUM) containing an excess of d-glucose did not allow the radiosynthesis of [{sup 18}F]FDG-RGD in activities >37 MBq in reasonable yield, rendering the direct use of clinical grade [{sup 18}F]FDG for the routine clinical synthesis of {sup 18}F-labelled peptides impossible. Using no-carrier-added (n.c.a.) [{sup 18}F]FDG obtained via HPLC separation of [{sup 18}F]FDGTUM from excess glucose, however, afforded [{sup 18}F]FDG-RGD in yields of 56-93% (decay corrected) and activities up to 37 MBq. Suitable reaction conditions were 20 min at 120 C and pH 2.5, and a peptide concentration of 5 mM. In a preliminary in vivo biodistribution study in M21 melanoma-bearing nude mice, [{sup 18}F]FDG-RGD showed increased tumour accumulation compared to the ''gold standard'' [{sup 18}F]galacto-RGD (2.18 vs 1.49 %iD/g, respectively, at 120 min after injection), but also slightly increased uptake in non-target organs, leading to comparable tumour/organ ratios for both compounds.??These data demonstrate that chemoselective {sup 18}F-labelling of aminooxy-functionalized peptides using n.c.a. [{sup 18}F]FDG represents a radiofluorination/glycosylation strategy that allows preparation of {sup 18}F-labelled peptides in high yield with suitable pharmacokinetics. As soon as the necessary n.c.a. preparation of [{sup 18}F]FDG prior to reaction with the Aoa-peptide can be implemented in a fully automated [{sup 18}F]FDG-synthesis, [{sup 18}F]fluoroglucosylation of peptides may represent a promising alternative to currently used chemoselective one-step {sup 18}F-labelling protocols. (orig.)}
doi = {10.1007/S00259-009-1122-0}
journal = {European Journal of Nuclear Medicine and Molecular Imaging}
issue = {9}
volume = {36}
place = {Germany}
year = {2009}
month = {Sep}
}