18F-labeling and biodistribution of the novel fluoro-quinolone antimicrobial agent, trovafloxacin (CP 99,219).
[18F]CP 99,219 [(1 alpha, 5 alpha, 6 alpha)-7-(6-amino-3-azabicyclo [3.1.0]hex-3-yl)-1-(2,4-difluorophenyl)-6-fluoro-1, 4-dihydro-4-oxo-1, 8-naphthyridine-3-carboxylic acid] was prepared by 18F for 19F exchange followed by reverse-phase HPLC purification. Studies of the effects of reaction time and temperature on 18F incorporation demonstrated that heating 1.0 mg of CP 99,219 in 0.5 cc of DMSO with 4.5 mg of K2CO3 and 24 mg of Kryptofix for 15 min at 160 degrees C results in the optimal compromise between radiochemical yield and purity. This method routinely provides radiochemical yields of 15-30% [EOS] with radiochemical purities of > 97%. Varying the concentration of CP 99,219 in the reaction mixture had no effect on yield. Biodistribution studies in rats demonstrated that significant concentrations of drug accumulate in most tissues. The tissues with the highest concentrations of drug were intestine, liver, kidney, and stomach.
Babich
J W
JW
Department of Radiology, Massachusetts General Hospital, Boston 02114, USA.
Rubin
R H
RH
Graham
W A
WA
Wilkinson
R A
RA
Vincent
J
J
Fischman
A J
AJ
D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D024841:Fluoroquinolones; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000890:Anti-Infective Agents; D005462:Fluorine Radioisotopes; D024841:Fluoroquinolones; D009287:Naphthyridines; C080163:trovafloxacin