Quantitative (19)F imaging of nmol-level F-nucleotides/-sides from 5-FU with T(2) mapping in mice at 9.4T.
A unique acquisition method is proposed for quantitative, high-sensitivity (19)F MR spectroscopic imaging for the study of drug distribution aiming at nmol-level metabolite information in mice. The use of fast spin echo (FSE) at 9.4T allowed us to obtain whole-body images with minimal effect of magnetic susceptibility and to acquire several metabolite signals simultaneously by the method of interleaved multifrequency selection. Modified 2-shot FSE was designed for simultaneous, high-sensitivity (19)F imaging and T(2) mapping. A time course study including all the main metabolites at 10-minute resolution was attained with an oral dose of 1-2 mmol 5-fluorouracil (5-FU) (130-260 mg)/kg in mice. With acquisition parameters optimized for in vivo T(2) of 40 ms, images of F-nucleotides/-sides, effective anabolites of the anticancer drug 5-FU, were obtained at the level of 200 nmol in the tumor for all the mice studied with a linear correlation (R = 0.96) between image intensity and the quantity determined in the excised tissue. The method exhibits potential capability of molecular imaging with a variety of (19)F-labeled compounds and drug evaluation.
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Yoshihiro
Y
Doi
Toshiyuki
T
Shimmura
Hideto
H
Kuribayashi
Yoshitsugu
Y
Tanaka
Yoko
Y
Kanazawa
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D008809:Mice, Inbred C3H; D009711:Nucleotides / Q000378:metabolism*; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D051598:Whole Body Imaging / Q000379:methods*
D000970:Antineoplastic Agents; D005462:Fluorine Radioisotopes; D009711:Nucleotides; D019275:Radiopharmaceuticals; D005472:Fluorouracil