Methyl 2-(2-[18F]fluoro-4-nitrobenzamido)-3-methylbutanoate

Excerpt

The most commonly used radiochemical for positron emission tomography (PET) imaging of brain or systemic cancerous tumors is 2-[¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG), a United States Food and Drug Administration approved imaging agent, but the use of this radiolabel is not without limitations because, among several application drawbacks, it tends to produce a high background in the brain and inflamed tissues during imaging (1, 2). To circumvent problems encountered with [¹⁸F]FDG, some investigators developed and evaluated unnatural amino acid (aa) derivatives such as O-2-[¹⁸F]fluoroethyl-L-tyrosine (L-[¹⁸F]FET) for the detection of tumors, particularly of the brain, and it was shown that L-[¹⁸F]FET was superior to [¹⁸F]FDG in distinguishing tumors from inflammation (3). However, the synthesis of ¹⁸F-labeled aa is cumbersome and, because an electrophilic substitution reaction is used to introduce the label into the aa, the final labeled product yields are very low (2). An alternative synthetic method of placing a fluoroalkyl group on the aromatic ring of tyrosine was observed to improve the yield of L-[¹⁸F]FET, but it prolonged the synthesis time for the radiochemical (4, 5). In an effort to simplify the synthesis of ¹⁸F-radiolabeled aas, ¹⁸F-labeled fluoroarylvaline derivatives of L-valine were prepared after modifying the aa with 2,4-dinitrobenzoic acid (2). According to the investigators, introduction of ¹⁸F at the ortho-position of 2,4-dinitrobenzoic acid is very easy, and the attachment of this moiety to L-valine results in an improved lipophilicity of the molecule. Using this method, two derivatives of L-valine were produced: methyl 2-(2-[¹⁸F]fluoro-4-nitrobenzamido)-3-methylbutanoate ([¹⁸F]MFNBMB; [¹⁸F]1) and methyl 2-(2-[¹⁸F]fluoro-4-nitrobenzamido)-3-methylbutanoic acid ([¹⁸F]FNBMBA; [¹⁸F]2) (2). These radiotracers were evaluated under in vivo conditions, and their biological properties were compared with those of [¹⁸F]FDG and L-[¹⁸F]FET. This chapter describes the characteristics of [¹⁸F]MFNBMB and its biodistribution in tumor-bearing mice. The characteristics of [¹⁸F]FNBMBA and its biodistribution in tumor-bearing mice is described in a separate chapter of MICAD (6).