Application of (19)F chemical shift imaging in studies of mice with orally administered 5-fluorouracil.
In vivo quantitative metabolic mapping is an ideal tool for pharmacokinetic studies. Oral 5-fluorouracil (5-FU) and its metabolites in mice were imaged simultaneously by the (19)F fast spin echo (FSE) sequence using interleaved frequency selection at 9.4T. However, 5-FU images in the small intestine have never been obtained regardless of concentration. The reason for the discrepancy between image intensity and concentration was T(2). At a pH above 6, a dramatic decrease in T(2) of a (19)F 5-FU signal in an aqueous solution was found; T(2) was shorter in the small intestine (14 ms) than in the stomach (52 ms). The (19)F CSI sequence in FID sampling mode was employed for detecting short T(2) signals. With a 13-min resolution time, the detection of the 5-FU signals in the region of the small intestine (0.6 mmol/kg) was successful with a 5 x 5 mm(2) in-plane resolution. Furthermore, two signals separated by 2 ppm were clearly distinguishable, but failed to be separately detectable with the (19)F FSE sequence. For quantitative simultaneous monitoring of 5-FU and its metabolites of varying T(2), the (19)F CSI sequence in FID sampling mode was found to be superior to the (19)F FSE sequence.
Kuribayashi
H
H
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. kurihide@pch.phar.kyushu-u.ac.jp
Doi
Y
Y
Kanazawa
Y
Y
D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D005260:Female; D005461:Fluorine; D005472:Fluorouracil / Q000008:administration & dosage*; D007091:Image Processing, Computer-Assisted; D007421:Intestine, Small / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D005461:Fluorine; D005472:Fluorouracil