A simplified synthesis of the hypoxia imaging agent 2-(2-Nitro-1 H -imidazol-1-yl)- N -(2,2,3,3,3-[18 F]pentafluoropropyl)-acetamide ([18 F]EF5)

Abstract Introduction [18 F]EF5 is a validated marker for PET imaging of tumor hypoxia. It is prepared by reacting a trifluoroallyl precursor with carrier-added [18 F]F2 gas in trifluoroacetic acid (TFA) solvent. We report here an improved radiosynthesis and purification of [18 F]EF5 by utilizing an...

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Bibliographic Details
Published in:Nuclear medicine and biology 2012-10, Vol.39 (7), p.1012-1018
Main Authors: Chitneni, Satish K, Bida, Gerald T, Dewhirst, Mark W, Zalutsky, Michael R
Format: Article
Language:English
Subjects:
[18F]EF5
Biological and medical sciences
Contrast media. Radiopharmaceuticals
Hypoxia
Medical sciences
Oasis® cartridge
On-line SPE
PET
Pharmacology. Drug treatments
Radiology
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Summary:Abstract Introduction [18 F]EF5 is a validated marker for PET imaging of tumor hypoxia. It is prepared by reacting a trifluoroallyl precursor with carrier-added [18 F]F2 gas in trifluoroacetic acid (TFA) solvent. We report here an improved radiosynthesis and purification of [18 F]EF5 by utilizing an electroformed nickel (Ni) target for [18 F]F2 production, and Oasis® HLB cartridges for on-line solid phase extraction of [18 F]EF5 prior to HPLC purification. Methods [18 F]F2 was produced by deuteron bombardment of neon plus F2 in an Ni target, and bubbled through the radiolabelling precursor solution. Purification was achieved by extracting the contents of the crude reaction mixture onto Oasis HLB cartridges, and subsequently eluted onto a semi-preparative HPLC column for further separation. Purified [18 F]EF5 was evaluated in small animal PET studies using HCT116 tumor xenografts in nude mice. Results The electroformed Ni target enabled recovery of > 75% of the radioactivity from the cyclotron target, resulting in 16.2 ± 2.2 GBq (438 ± 58 mCi) of [18 F]F2 available for the synthesis. Use of Oasis cartridges yielded a less complex mixture for purification. On average, 1140 ± 200 MBq (30.8 ± 5.4 mCi) of [18 F]EF5 were collected at EOS. Small animal PET imaging studies showed specific retention of [18 F]EF5 in tumors, with tumor-to-muscle ratios of 2.7 ± 0.3 at about160 min after injection. Conclusion A simple procedure has been developed for the routine synthesis of [18 F]EF5 in amounts and purity required for clinical studies. This new method avoids the need for TFA evaporation and also enables facile automation of the synthesis using commercially available radiosynthesis modules.
ISSN:0969-8051
1872-9614
DOI:10.1016/j.nucmedbio.2012.05.006