Degradation of acetonitrile in eluent solutions for [18F]fluoride PET chemistry: impact on radiosynthesis of [18F]FACBC and [18F]FDG

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 55; no. 3; pp. 97 - 102
• Main Authors: Svadberg, Anders, Wickstrøm, Torild, Hjelstuen, Ole Kristian
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.03.2012; Wiley
• Subjects: [18F]fluoride; acetate; Biochemical Research Methods; Biochemistry & Molecular Biology; Biological and medical sciences; Chemistry; Chemistry, Analytical; Chemistry, Medicinal; Contrast media. Radiopharmaceuticals; degradation; eluent; Life Sciences & Biomedicine; Medical sciences; methanol; PET; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; Science & Technology; acetate; F-18 FLUORIDE; methanol; degradation; [18F]fluoride; PET; eluent; [; F]fluoride
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.1956

In [18F]fluoride chemistry, an eluent solution containing a weak aqueous base is used to release [18F]fluoride after adsorption on an anion exchange resin. Traditionally, the eluent solution is freshly prepared, but modern PET tracer manufacturers may utilize the benefits of preparing bulk solutions or prefilled vials for storage. We discovered that typical eluent solutions containing kryptofix and K2CO3 in aqueous acetonitrile degraded upon storage. Acetonitrile will at alkaline pH hydrolyse to acetamide and ammonium acetate. Acetate may serve as a competing nucleophile to [18F]fluoride. Eluent solutions used in the synthesis of [18F]FACBC and [18F]FDG generated mg/ml levels of acetamide and ammonium acetate during storage at room temperature or above. The synthesis of [18F]FACBC was prone to eluent degradation, with gradual reduction of radiochemical yield (RCY) from 62.5% to 44.7% during 12 months of storage at 30 °C. The synthesis of [18F]FDG was only affected when the eluent was stored at 50 °C, reducing the RCY from 86.8% to 66.7% after 3 months of storage. For degradation effects to be avoided, an alternative eluent solution with no acetonitrile was investigated in the synthesis of [18F]FACBC. A methanol‐based eluent was successfully made, showing no degradation and unchanged RCY after 6 months of storage at 50 °C. Copyright © 2012 John Wiley & Sons, Ltd. We discovered that typical eluent solutions containing K222 and K2CO3 in aqueous acetonitrile, degraded relatively quickly upon storage. Acetonitrile hydrolyse into acetamide and ammonium acetate. Acetamide is a known carcinogen and acetate can serve as a competing nucleophile. These implications were investigated in the synthesis of [18F]FDG and [18F]FACBC. An alternative eluent with methanol instead of acetonitrile was developed.