Synthesis and biodistribution of 18F-labeled fleroxacin.
[18F]Fleroxacin (6,8-difluoro-1,4-dihydro-1-(2-[18F]fluoroethyl)-4- oxo-7-(4-methyl-1-piperazinyl)-3-quinolinecarboxylic acid) was synthesized from its methylsulfonyl ester precursor. 6,7,8-Trifluoro-4-hydroxyquinoline-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-quinolinecarboxyl ic acid ethyl ester in 76% yield which was then condensed with 1-methyl-piperazine to produce 6,8-difluoro-1,4-dihydro-1-(2-hydroxyethyl)-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 18F- in the presence of Kryptofix 2.2.2 followed by basic hydrolysis produced [18F]fleroxacin with a radiochemical yield of 5-8% [EOS] within 90 min. The pattern of biodistribution of [18F]fleroxacin was similar to the 14C-labeled drug.
Livni
E
E
Department of Radiology, Massachusetts General Hospital, Boston 02114.
Babich
J
J
Alpert
N M
NM
Liu
Y Y
YY
Thom
E
E
Cleeland
R
R
Prosser
B L
BL
Correia
J A
JA
Strauss
H W
HW
Rubin
R H
RH
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D016576:Fleroxacin / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D011874:Radiometry; D014018:Tissue Distribution
D005462:Fluorine Radioisotopes; D016576:Fleroxacin