18F-AFETP、18F-FET 和 18F-FDG 对小鼠 DBT 脑胶质瘤的成像研究。
18F-AFETP, 18F-FET, and 18F-FDG imaging of mouse DBT gliomas.
机构信息
Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA.
出版信息
J Nucl Med. 2013 Jul;54(7):1120-6. doi: 10.2967/jnumed.112.113217. Epub 2013 May 6.
UNLABELLED
The goal of this study was to evaluate the (18)F-labeled nonnatural amino acid (S)-2-amino-3-[1-(2-(18)F-fluoroethyl)-1H-[1,2,3]triazol-4-yl]propanoic acid ((18)F-AFETP) as a PET imaging agent for brain tumors and to compare its effectiveness with the more-established tracers O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) and (18)F-FDG in a murine model of glioblastoma. The tracer (18)F-AFETP is a structural analog of histidine and is a lead compound for imaging cationic amino acid transport, a relatively unexplored target for oncologic imaging.
METHODS
(18)F-AFETP was prepared using the click reaction. BALB/c mice with intracranially implanted delayed brain tumor (DBT) gliomas (n = 4) underwent biodistribution and dynamic small-animal PET imaging for 60 min after intravenous injection of (18)F-AFETP. Tumor and brain uptake of (18)F-AFETP were compared with those of (18)F-FDG and (18)F-FET through small-animal PET analyses.
RESULTS
(18)F-AFETP demonstrated focally increased uptake in tumors with good visualization. Peak tumor uptake occurred within 10 min of injection, with stable or gradual decrease over time. All 3 tracers demonstrated relatively high uptake in the DBTs throughout the study. At late time points (47.5-57.5 min after injection), the average standardized uptake value with (18)F-FDG (1.9 ± 0.1) was significantly greater than with (18)F-FET (1.1 ± 0.1) and (18)F-AFETP (0.7 ± 0.2). The uptake also differed substantially in normal brain, with significant differences in the standardized uptake values at late times among (18)F-FDG (1.5 ± 0.2), (18)F-FET (0.5 ± 0.05), and (18)F-AFETP (0.1 ± 0.04). The resulting average tumor-to-brain ratio at the late time points was significantly higher for (18)F-AFETP (7.5 ± 0.1) than for (18)F-FDG (1.3 ± 0.1) and (18)F-FET (2.0 ± 0.3).
CONCLUSION
(18)F-AFETP is a promising brain tumor imaging agent, providing rapid and persistent tumor visualization, with good tumor-to-normal-brain ratios in the DBT glioma model. High tumor-to-brain, tumor-to-muscle, and tumor-to-blood ratios were observed at 30 and 60 min after injection, with higher tumor-to-brain ratios than obtained with (18)F-FET or (18)F-FDG. These results support further development and evaluation of (18)F-AFETP and its derivatives for tumor imaging.
未加说明
本研究旨在评估（18）F 标记的非天然氨基酸（S）-2-氨基-3-[1-[2-（18）F-氟乙基]-1H-[1,2,3]三唑-4-基]丙酸（（18）F-AFETP）作为脑肿瘤的 PET 成像剂，并与更成熟的示踪剂 O-[2-（18）F-氟乙基]-L-酪氨酸（（18）F-FET）和（18）F-FDG 在胶质母细胞瘤的小鼠模型中进行比较。示踪剂（18）F-AFETP 是组氨酸的结构类似物，是用于成像阳离子氨基酸转运的先导化合物，这是肿瘤成像中一个相对未被探索的目标。
方法
使用点击反应制备（18）F-AFETP。BALB/c 小鼠颅内植入延迟性脑肿瘤（DBT）胶质瘤（n=4），静脉注射（18）F-AFETP 后进行 60 分钟的生物分布和小动物 PET 成像。通过小动物 PET 分析比较（18）F-AFETP 与（18）F-FDG 和（18）F-FET 的肿瘤和脑摄取。
结果
（18）F-AFETP 显示肿瘤有局灶性摄取增加，可视化效果良好。肿瘤摄取的峰值出现在注射后 10 分钟内，随着时间的推移逐渐稳定或逐渐下降。所有 3 种示踪剂在整个研究中均在 DBT 中表现出较高的摄取。在晚期（注射后 47.5-57.5 分钟），（18）F-FDG 的平均标准化摄取值（1.9±0.1）明显大于（18）F-FET（1.1±0.1）和（18）F-AFETP（0.7±0.2）。在正常脑组织中摄取也有很大差异，在晚期时间点，（18）F-FDG（1.5±0.2）、（18）F-FET（0.5±0.05）和（18）F-AFETP（0.1±0.04）之间的标准化摄取值存在显著差异。晚期时，（18）F-AFETP 的平均肿瘤与脑比值（7.5±0.1）明显高于（18）F-FDG（1.3±0.1）和（18）F-FET（2.0±0.3）。
结论
（18）F-AFETP 是一种很有前途的脑肿瘤成像剂，可快速持久地可视化肿瘤，在 DBT 胶质母细胞瘤模型中具有良好的肿瘤与正常脑比值。在注射后 30 分钟和 60 分钟观察到高肿瘤与脑、肿瘤与肌肉和肿瘤与血液的比值，并且肿瘤与脑的比值高于（18）F-FET 或（18）F-FDG。这些结果支持进一步开发和评估（18）F-AFETP 及其衍生物用于肿瘤成像。
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