The Effect of Reaction Media and Phase Transfer Catalyst on the Fluorination Yield and Enantiomeric Purity in Asymmetric Synthesis of O-(2'-[18F]fluoroethyl)-LTyrosine ([18F]FET)

Author(s): Raisa Krasikova, Victoria Orlovskaya, Maria Stepanova, Olga Fedorova.

Journal Name: Current Organic Chemistry

Volume 17 , Issue 19 , 2013

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Abstract:

Due to favourable in-vivo characteristics, the long half-life of 18F (110 min) allowing for remote-site delivery and its high specificity, O-(2’-[18F]fluoroethyl)-L-tyrosine ([18F]FET) has gained increased importance for molecular imaging of cerebral tumors. Consequently, the development of simple and efficient production strategies for FET could be an important step to further improve the cost-effective availability of FET in the clinical environment. An earlier developed labeling approach using a chiral NiII complex of an alkylated (S)-tyrosine Schiff base, Ni-(S)-BPB-(S)-Tyr-OCH2CH2OTs (II) as a synthesis precursor provided a good means of preparing FET in high enantiomeric purity of 94-97%, but in moderate RCY. The aim of this study was to improve the 18F-fluorination efficiency of (II) by varying fluorinations conditions: reaction media (non protic and protic solvents), PTC/base system and temperature. A very high 18F-fluoride incorporation rate into (II) was achieved in kryptofix-mediated fluorinations in DMSO, however this route did not allow FET in high and reproducible enantiomeric purity that is essential for application in PET human studies. The attempted 18F-fluorination of (II) in tert-alcohols resulted in poor (t-BuOH) or moderate (t-amyl alcohol) incorporation rates and associated with difficulties in the process automation. From our current results we may conclude that the earlier developed acetonitrile/K2.2.2 remains the most appropriate solvent/ catalyst combination for use in the 18F-fluorination reaction for the preparation of enantiomerically pure FET starting from (II).

Keywords: 18F, fluorine-18 radiolabeling, Protic solvents fluorination, O-(2-[18F]fluoroethyl)-L-tyrosine, [18F]FET, Asymmetric synthesis, Brain tumors PET imaging.

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Article Details

VOLUME: 17
ISSUE: 19
Year: 2013
Page: [2159 - 2163]
Pages: 5
DOI: 10.2174/13852728113179990108
Price: $58

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