SYNTHESIS AND BIODISTRIBUTION OF F-18 LABELED FLEROXACIN

[F-18]Fleroxacin (6,8-difluoro-1,4-dihydro-1-(2-[F-18]fluoroethyl)-4-oxo-7-(4-methyl-1-piperazinyl)-3-quinolinecarboxylic acid) was synthesized from its methylsulfonyl ester precursor. 6.7,8-Trifluoro-4-hydroxy-quinoline-3-carboxylic acid ethyl ester (Ro 19-7423) was alkylated with 2-bromoethanol to produce 6,7,8-trifluoro-1,4-dihydro-1-(2-hydroxyethyl)-4-oxo-3-quinolinecarboxylic acid ethyl ester in 76% yield which was then condensed with 1-methyl-piperazine to produce 6,8-difluoro-1,4-dihydro-1-(2-hydroxy-ethyl)-7-(4-methyl-1-piperazinyl)4-oxo-3-quinolinecarboxylic acid ethyl ester in 67% yield. This product was reacted with methanesulfonyl chloride to produce the mesylate precursor of fleroxacin in 66% yield. Nucleophilic substitution of the mesylate with F-18 in the presence of Kryptofix(R) 2.2.2 followed by basic hydrolysis produced [F-18]fleroxacin with a radiochemical yield of 5-8% [EOS] within 90 min, The pattern of biodistribution of [F-18]fleroxacin was similar to the C-14-labeled drug.