Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Magn Reson Med. 2009 Nov;62(5):1129-39. doi: 10.1002/mrm.22075.
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.
提出了一种独特的定量、高灵敏度(19)F 磁共振波谱成像获取方法,用于研究药物分布,旨在获取小鼠体内纳摩尔级代谢物信息。在 9.4T 场强下使用快速自旋回波(FSE),我们能够获得最小磁敏感性影响的全身图像,并通过交错多频选择方法同时获取多个代谢物信号。设计了改进的 2 -shot FSE 用于同时进行高灵敏度(19)F 成像和 T2 映射。通过给小鼠口服 1-2mmol 5-氟尿嘧啶(5-FU)(130-260mg)/kg,在 10 分钟的时间分辨率内实现了所有主要代谢物的时程研究。在体内 T2 优化为 40ms 的采集参数下,在所有研究的小鼠肿瘤中,F-核苷酸/F-侧链(抗癌药物 5-FU 的有效合成代谢物)的图像在 200nmol 水平获得,图像强度与组织切除后定量之间存在线性相关性(R=0.96)。该方法具有通过各种(19)F 标记化合物进行分子成像和药物评估的潜力。