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

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 39; no. 4; pp. 319 - 330
• Main Authors: Dolle, F, Hinnen, F, Vaufrey, F, Tavitian, B, Crouzel, C
• Format: Journal Article
• Language: English
• Published: W SUSSEX Wiley 01.04.1997
• Subjects: Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry; Chemistry, Analytical; Chemistry, Medicinal; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; fluorine-18; F-18-LABELED 5-FLUOROURACIL; labeled oligodeoxynucleotide; mRNA; PROLIFERATION; hybridization; positron emission tomography; antisense; PROBES
• ISSN: 0362-4803
• DOI: 10.1002/(SICI)1099-1344(199704)39:4<319::AID-JLCR970>3.0.CO;2-7

This paper describes an original general method for the synthesis of oligodeoxynucleotides (ODNs) carrying the positron emitter F-18. 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 Br-76 or I-123. 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 [F-18]N-(4-fluorobenzyl)-2-(ACCGATCCG(3')-p(s))-acetamid [F-18]-(1) (around 30 mCi or 1.1 GBq) were obtained for the whole synthetic procedure (220 minutes) with respect to [F-18]fluoride ion, with specific radioactivities as high as 3 Ci/mu mole (111 TBq/mu mol) calculated for End of Bombardment (or 750 mCi/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 16 MeV proton beam [O-18(p,n)F-18].