A novel prosthetic group for site-selective labeling of peptides for positron emission tomography.
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.
Olberg
Dag Erlend
DE
Institute of Pharmacy, Department of Pharmaceutics and Biopharmaceutics, University of Tromsø, N- 9037 Tromsø, Norway. dag.erlend.olberg@farmasi.uit.no
Hjelstuen
Ole Kristian
OK
Solbakken
Magne
M
Arukwe
Joseph
J
Karlsen
Hege
H
Cuthbertson
Alan
A
D000085:Acetates / Q000737:chemistry; D001665:Binding Sites; D002021:Buffers; D005462:Fluorine Radioisotopes; D006863:Hydrogen-Ion Concentration; D006898:Hydroxylamines / Q000737:chemistry; D008301:Maleimides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D049268:Positron-Emission Tomography; D011854:Radiochemistry; D013194:Staining and Labeling / Q000379:methods*; D013379:Substrate Specificity; D013696:Temperature; D013997:Time Factors
D000085:Acetates; D002021:Buffers; D005462:Fluorine Radioisotopes; D006898:Hydroxylamines; D008301:Maleimides; D010455:Peptides