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This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Olberg, D. Articles by Cuthbertson, A. PubMed Articles by Olberg, D. Articles by Cuthbertson, A.

A novel prosthetic group for site-selective labeling of peptides for positron emission tomography

¹ Department of Pharmaceutics & Biopharmaceutics, University of Tromsø, Tromsø, Norway; ² GE Healthcare, Medical Diagnostics Discovery Research, Oslo, Norway

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Objectives: The purpose of this study was to investigate a novel chemoselective ligation reaction comprising conjugation of an [¹⁸F]-N-methylaminooxy-containing prosthetic group to functionalized peptides.

Methods: 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 towards the N-methylaminooxy group. Conjugation reactions were initially carried out with non-radioactive precursors, only the most promising pairings progressing to full radiochemical assessment with ¹⁸F.

Results: Best results were obtained for the ligation of O-[2-(2-[¹⁸F]fluoroethoxy)ethyl]-N-methyl-N-hydroxylamine to the maleimidopropionyl-Lys-Gly-Phe-Gly-Lys-OH precursor in acetate buffer (pH 5) after 1 h at 70 °C. The non-decay-corrected isolated yield was calculated to be 8.5 %. The most encouraging result was observed with 4-(2-nitrovinyl)benzoyl-Lys-Gly-Phe-Gly-Lys-OH, where the conjugation reaction proceeded rapidly to completion at 30 °C after only 5 min. The corresponding non-decay corrected radiochemical yield for the isolated ¹⁸F-labeled product was 12 %. The preliminary results from this study demonstrate the considerable potential of this novel strategy for the radiolabeling of peptides.

Conclusions: ¹⁸F-Containing N-methylaminooxy compounds are useful prosthetic groups suitable for labeling of peptides. The 4-(2-nitrovinyl)benzoyl moiety covalently linked to a model peptide was found to be highly reactive and selective towards the prosthetic group enabling efficient labeling at 30 °C after 5 minutes in sodium acetate buffer at pH 5. This protocol therefore represents a novel methodology for the radiolabeling of peptides.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Olberg, D. Articles by Cuthbertson, A. PubMed Articles by Olberg, D. Articles by Cuthbertson, A.