A general method for labeling oligodeoxynucleotides with 18F for in vivo PET imaging

Abstract

This paper describes an original general method for the synthesis of oligodeoxynucleotides (ODNs) carrying the positron emitter 18F. The labeling strategy developed is simple, reliable, independent of backbone modifications and base sequence. It should be of general applicability for the labeling of natural or modified ODN, provided that the latter bear a phosphorothioate group at their 3′ end, and it should be easily transposable to other radiohalogenes such as 76Br or 123I. The methodology we developed uses recently preparative-scale commercially available 3′-phosphorothioate oligodeoxynucleotides and is based on the efficient coupling reaction of oligodeoxynucleotides, containing a single phosphorothioate monoester, and N-(4-radiohalobenzyl)-2-bromoacetamide. Yields of 40–45% (decay corrected) of pure [18F]N-(4-fluorobenzyl)-2-(ACCGATCCG3′-ps)-acetamide [18F]-(1) (around 30 mCi or 1.1 GBq) were obtained for the whole synthetic procedure (220 minutes) with respect to [18F]fluoride ion, with specific radioactivities as high as 3 Ci/μmole (111 TBq/μmol) calculated for End of Bombardment (or 750 mCi/μmole (28 TBq/μmol) at End of Synthesis) for a 15 μA, 60 min (54000 μC) irradiation of a 50% [18O]-enriched water target with a 16 MeV proton beam [18O(p,n)18F]. © 1997 John Wiley & Sons, Ltd.