Kong Fan-Lin, Zhang YinHan, Ali Mohammad S, Oh Chanksok, Mendez Richard, Kohanim Saady, Tsao Ning, Chanda Mithu, Huang Wen-Chien, Yang David J
Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Holcombe Boulevard, Houston, Texas 77030, USA.
Nucl Med Commun. 2010 Aug;31(8):699-707. doi: 10.1097/MNM.0b013e328339ea48.
This study was to develop a (99m)Tc-labeled alpha-methyl tyrosine (AMT) using L,L-ethylenedicysteine (EC) as a chelator and to evaluate its potential in breast tumor imaging in rodents.
EC-AMT was synthesized by reacting EC and 3-bromopropyl AMT (N-BOC, ethyl ester) in ethanol/potassium carbonate solution. EC-AMT was labeled with (99m)Tc in the presence of tin (II) chloride. Rhenium-EC-AMT (Re-EC-AMT) was synthesized as a reference standard for (99m)Tc-EC-AMT. To assess the cellular uptake kinetics of (99m)Tc-EC-AMT, 13 762 rat breast cancer cells were incubated with (99m)Tc-EC-AMT for 0-2 h. To investigate the transport mechanism, the same cell line was used to conduct the competitive inhibition study using L-tyrosine. Tissue distribution of (99m)Tc-EC-AMT was determined in normal rats at 0.5-4 h. Planar imaging of breast tumor-bearing rats was performed at 30 and 90 min. The data were compared with those of (18)F-2-fluoro-2-deoxy-glucose. Blocking uptake study using unlabeled AMT was conducted to investigate the transport mechanism of (99m)Tc-EC-AMT in vivo.
Structures of EC-AMT and Re-EC-AMT were confirmed by nuclear magnetic resonance, high performance liquid chromatography and mass spectra. In-vitro cellular uptake of (99m)Tc-EC-AMT in 13,762 cells was increased as compared with that of (99m)Tc-EC and could be inhibited by L-tyrosine. Biodistribution in normal rats showed high in-vivo stability of (99m)Tc-EC-AMT. Planar scintigraphy at 30 and 90 min showed that (99m)Tc-EC-AMT could clearly visualize tumors. (99m)Tc-EC-AMT uptake could be significantly blocked by unlabeled AMT in vivo.
The results indicate that (99m)Tc-EC-AMT, a new amino acid transporter-based radiotracer, is suitable for breast tumor imaging.
本研究旨在以L,L-乙二巯基半胱氨酸（EC）作为螯合剂，开发一种（99m）Tc标记的α-甲基酪氨酸（AMT），并评估其在啮齿动物乳腺肿瘤成像中的潜力。
通过在乙醇/碳酸钾溶液中使EC与3-溴丙基AMT（N-BOC，乙酯）反应合成EC-AMT。在氯化亚锡存在下用（99m）Tc标记EC-AMT。合成铼-EC-AMT（Re-EC-AMT）作为（99m）Tc-EC-AMT的参考标准品。为评估（99m）Tc-EC-AMT的细胞摄取动力学，将13762个大鼠乳腺癌细胞与（99m）Tc-EC-AMT孵育0至2小时。为研究转运机制，使用同一细胞系用L-酪氨酸进行竞争抑制研究。在0.5至4小时测定正常大鼠体内（99m）Tc-EC-AMT的组织分布。对荷乳腺肿瘤大鼠在30分钟和90分钟进行平面成像。将数据与（18）F-2-氟-2-脱氧葡萄糖的数据进行比较。使用未标记的AMT进行阻断摄取研究以研究（99m）Tc-EC-AMT在体内的转运机制。
通过核磁共振、高效液相色谱和质谱确认了EC-AMT和Re-EC-AMT的结构。与（99m）Tc-EC相比，13762个细胞中（99m）Tc-EC-AMT的体外细胞摄取增加，并且可被L-酪氨酸抑制。在正常大鼠中的生物分布显示（99m）Tc-EC-AMT在体内具有高稳定性。30分钟和90分钟的平面闪烁显像显示（99m）Tc-EC-AMT可清晰显示肿瘤。未标记的AMT在体内可显著阻断（99m）Tc-EC-AMT的摄取。
结果表明（99m）Tc-EC-AMT，一种新型基于氨基酸转运体的放射性示踪剂，适用于乳腺肿瘤成像。
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