一项体内19F核磁共振研究显示，与门静脉输注相比，肝动脉输注在预防5-氟尿嘧啶分解代谢方面具有优越性。

Superiority of hepatic arterial infusion in preventing catabolism of 5-FU compared with portal vein infusion revealed by an in vivo 19F NMR study.

作者信息

Okuno K, Hirai N, Lee Y S, Tarabar D, Ueno H, Yasutomi M

机构信息

First Department of Surgery, Kinki University School of Medicine, Osaka-sayama, Osaka, Japan.

出版信息

Cancer Chemother Pharmacol. 1998;42(4):341-4. doi: 10.1007/s002800050827.

DOI:10.1007/s002800050827

PMID:9744781

Abstract

PURPOSE

The aim of this study was to identify the route of administration of 5-FU with the greatest pharmacological advantage in a rat model using non-invasive in vivo 19F nuclear magnetic resonance (NMR) spectroscopy.

METHODS

5-FU (50 mg/kg) was administered to anesthetized Wistar rats cannulated into the hepatic artery, portal vein or tail vein and 11 NMR spectra were acquired from the liver region to 60.5 min every 5.5 min.

RESULTS

With systemic i.v. (tail vein) infusion, the 19F-NMR signal for 5-FU from the liver region peaked in the first spectrum (0-5.5 min), and then gradually decreased. The signal for the 5-FU catabolite alpha-fluoro-beta-alanine (FBAL) gradually increased to the sixth spectrum (0-33.0 min) and then plateaued. Following portal vein infusion the intensity of the first 5-FU spectrum was twice as high as that following i.v. infusion, but the intensity decreased and the FBAL signal increased gradually in the sixth spectrum as systemic i.v. infusion. In contrast, the intensity of the 5-FU signal following hepatic artery infusion was the same as that following portal vein infusion in the first spectrum, and maintained a strong intensity to the final spectrum (60.5 min). The FBAL signal was detected from the second spectrum following hepatic artery infusion, but its intensity was significantly weaker than that following i.v. or portal vein infusion.

CONCLUSIONS

Hepatic arterial infusion resulted in the active form of 5-FU being present for a longer time and its degradation in the liver being suppressed compared with the results following portal vein infusion. This catabolic advantage of hepatic arterial infusion could lead to a more potent anti-tumor activity against liver metastases, but could also lead to significant host toxicity including biliary toxicity. We recommend that the dose/schedule of 5-FU administered via the hepatic artery should be adjusted carefully.

摘要

目的

本研究旨在利用非侵入性体内19F核磁共振（NMR）光谱法，在大鼠模型中确定具有最大药理学优势的5-氟尿嘧啶给药途径。

方法

将5-氟尿嘧啶（50mg/kg）给予经肝动脉、门静脉或尾静脉插管的麻醉Wistar大鼠，并每隔5.5分钟从肝脏区域采集11个NMR光谱，持续60.5分钟。

结果

通过全身静脉（尾静脉）输注，肝脏区域5-氟尿嘧啶的19F-NMR信号在第一个光谱（0-5.5分钟）达到峰值，然后逐渐下降。5-氟尿嘧啶分解代谢产物α-氟-β-丙氨酸（FBAL）的信号逐渐增加至第六个光谱（0-33.0分钟），然后趋于平稳。门静脉输注后，第一个5-氟尿嘧啶光谱的强度是静脉输注后的两倍，但在第六个光谱中强度降低，FBAL信号如全身静脉输注一样逐渐增加。相比之下，肝动脉输注后5-氟尿嘧啶信号的强度在第一个光谱中与门静脉输注后的相同，并在最后一个光谱（60.5分钟）保持较强强度。肝动脉输注后从第二个光谱中检测到FBAL信号，但其强度明显弱于静脉或门静脉输注后的强度。