A GENERAL-METHOD FOR LABELING OLIGODEOXYNUCLEOTIDES WITH F-18 FOR IN-VIVO PET IMAGING

This paper describes an original general method for the synthesis of o ligodeoxynucleotides (ODNs) carrying the positron emitter F-18. The la beling strategy developed is simple, reliable, independent of backbone modifications and base sequence. It should be of general applicabilit y for the labeling of natural or modified ODN, provided that the latte r bear a phosphorothioate group at their 3' end, and it should be easi ly transposable to other radiohalogenes such as Br-76 or I-123. The me thodology we developed uses recently preparative-scale commercially av ailable 3'-phosphorothioate oligodeoxynucleotides and is based on the efficient coupling reaction of oligodeoxynucleotides, containing a sin gle phosphorothioate monoester, and N-(4-radiohalobenzyl)-2-bromoaceta mide. Yields of 40-45% (decay corrected) of pure N-(4-fluorobenzyl)-2- (ACCGATCCG(3')-p(s))-acetamid [F-18]-(1) (around 30 mCi or 1.1 GBq) we re obtained for the whole synthetic procedure (220 minutes) with respe ct to [F-18]fluoride ion, with specific radioactivities as high as 3 C i/mu mole (111 TBq/mu mol) calculated for End of Bombardment (or 750 m Ci/mu mole (28 TBq/mu mol) at End of Synthesis) for a 15 mu A, 60 min (54000 mu C)irradiation of a 50% [O-18]-enriched water target with a 1 6 MeV proton beam [O-18(p,n)F-18].