L-3-[氟-18]氟-α-甲基酪氨酸的生物分布研究：一种潜在的肿瘤检测剂。

Biodistribution studies on L-3-[fluorine-18]fluoro-alpha-methyl tyrosine: a potential tumor-detecting agent.

作者信息

Inoue T, Tomiyoshi K, Higuichi T, Ahmed K, Sarwar M, Aoyagi K, Amano S, Alyafei S, Zhang H, Endo K

机构信息

Department of Nuclear Medicine, Gunma University School of Medicine, Japan.

出版信息

J Nucl Med. 1998 Apr;39(4):663-7.

PMID:9544678

Abstract

UNLABELLED

Iodine-123-alpha-methyl tyrosine has proven to be a promising SPECT agent for imaging amino acid uptake in tumors. We developed L-[3-(18)F]-alpha-methyl tyrosine (FMT) for PET studies. The aim of this study was to investigate its potential use as a tumor-detecting agent by using tumor-bearing mice.

METHODS

We investigated the biodistribution in normal BALB/C mice and BALB/cA nude mice bearing human rectal cancer cell line (LS180) until 120 min postinjection. FMT tumor uptake at 60 min postinjection in mice with LS180 rectal cancer, RPM11788 B-cell lymphoma and MCF7 mammary cell carcinoma was assessed, and the results were compared with 18F-fluoro-2-deoxy-D-glucose (FDG) tumor uptake. The effect of competitive inhibition of large neutral amino acid transport system using unlabeled L-alanine was also investigated.

RESULTS

The amount of FMT in blood fell to 1.05%ID/20 g at 60 min postinjection, whereas that in the pancreas was 15.2%ID/20 g, resulting in a high pancreas-to-blood ratio of 14.5. In other organs, initial uptake peaked at 5 min postinjection and then declined with time. In LS180 tumor-bearing mice, peak FMT uptake in tumor was observed at 60 min postinjection. Tumor-to-blood and tumor-to-muscle ratios ranged from 1.60 to 2.94 and from 2.79 to 3.25 over the 120-min observation period. Tumor uptake of FMT was clearly reduced by inhibition of the amino acid transport system. In mice with LS180 and MCF7 tumors, FMT tumor uptake at 60 min postinjection was significantly higher than FDG tumor uptake, whereas in RPM11788 lymphoma, uptake of FDG was significantly higher than FMT tumor uptake. Tumor-to-blood ratios of FMT in mice with LS180, RPMI1788 and MCF7 tumor at 60 min postinjection were 1.82, 5.88 and 3.56, respectively.

CONCLUSION

FMT, like other fluorinated amino acids, may become a promising tumor-detecting agent for PET, assuming that efficient methods of radiosynthesis are developed.

摘要

未标记

碘-123-α-甲基酪氨酸已被证明是一种用于肿瘤氨基酸摄取成像的有前景的单光子发射计算机断层显像（SPECT）剂。我们开发了用于正电子发射断层显像（PET）研究的L-[3-(18)F]-α-甲基酪氨酸（FMT）。本研究的目的是通过使用荷瘤小鼠来研究其作为肿瘤检测剂的潜在用途。

方法

我们研究了正常BALB/C小鼠和荷人直肠癌细胞系（LS180）的BALB/cA裸鼠直至注射后120分钟的生物分布。评估了注射后60分钟时LS180直肠癌、RPM11788 B细胞淋巴瘤和MCF7乳腺癌小鼠中FMT的肿瘤摄取情况，并将结果与18F-氟-2-脱氧-D-葡萄糖（FDG）的肿瘤摄取情况进行比较。还研究了使用未标记的L-丙氨酸竞争性抑制大中性氨基酸转运系统的效果。

结果

注射后60分钟时，血液中FMT的量降至1.05%ID/20 g，而胰腺中的量为15.2%ID/20 g，导致胰腺与血液的高比值为14.5。在其他器官中，初始摄取在注射后5分钟达到峰值，然后随时间下降。在荷LS180肿瘤的小鼠中，注射后60分钟观察到肿瘤中FMT摄取峰值。在120分钟的观察期内，肿瘤与血液和肿瘤与肌肉的比值范围分别为1.60至2.94和2.79至3.25。氨基酸转运系统的抑制明显降低了FMT的肿瘤摄取。在患有LS180和MCF7肿瘤的小鼠中，注射后60分钟时FMT的肿瘤摄取明显高于FDG的肿瘤摄取，而在RPM11788淋巴瘤中，FDG的摄取明显高于FMT的肿瘤摄取。注射后60分钟时，患有LS180、RPMI1788和MCF7肿瘤的小鼠中FMT的肿瘤与血液比值分别为1.82、5.88和3.56。