Kong Fan-Lin, Ali Mohammad S, Rollo Alex, Smith Daniel L, Zhang Yinhan, Yu Dong-Fang, Yang David J
Department of Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
J Biomed Biotechnol. 2012;2012:671708. doi: 10.1155/2012/671708. Epub 2012 Mar 5.
The purpose of this study was to develop an efficient way to synthesize (99m)Tc-O-[3-(1,4,8,11-tetraazabicyclohexadecane)-propyl]-tyrosine ((99m)Tc-N4-Tyrosine), a novel amino acid-based radiotracer, and evaluate its potential in breast cancer gamma imaging. Precursor N4-Tyrosine was synthesized using a 5-step procedure, and its total synthesis yield was 38%. It was successfully labeled with (99m)Tc with high radiochemical purity (>95%). Cellular uptake of (99m)Tc-N4-Tyrosine was much higher than that of (99m)Tc-N4 and the clinical gold standard (18)F-2-deoxy-2-fluoro-glucose ((18)F-FDG) in rat breast tumor cells in vitro. Tissue uptake and dosimetry estimation in normal rats revealed that (99m)Tc-N4-Tyrosine could be safely administered to humans. Evaluation in breast tumor-bearing rats showed that although (99m)Tc-N4-Tyrosine appeared to be inferior to (18)F-FDG in distinguishing breast tumor tissue from chemical-induced inflammatory tissue, it had high tumor-to-muscle uptake ratios and could detect breast tumors clearly by planar scintigraphic imaging. (99m)Tc-N4-Tyrosine could thus be a useful radiotracer for use in breast tumor diagnostic imaging.
本研究的目的是开发一种高效的方法来合成新型氨基酸基放射性示踪剂（99m）Tc-O-[3-（1,4,8,11-四氮杂双环十六烷）-丙基]-酪氨酸（（99m）Tc-N4-酪氨酸），并评估其在乳腺癌γ成像中的潜力。前体N4-酪氨酸通过五步程序合成，其总合成产率为38%。它成功地用（99m）Tc标记，放射化学纯度高（>95%）。在体外大鼠乳腺肿瘤细胞中，（99m）Tc-N4-酪氨酸的细胞摄取远高于（99m）Tc-N4和临床金标准（18）F-2-脱氧-2-氟葡萄糖（（18）F-FDG）。正常大鼠的组织摄取和剂量学估计表明，（99m）Tc-N4-酪氨酸可以安全地用于人体。对荷乳腺肿瘤大鼠的评估表明，虽然（99m）Tc-N4-酪氨酸在区分乳腺肿瘤组织和化学诱导的炎症组织方面似乎不如（18）F-FDG，但它具有高的肿瘤与肌肉摄取比，并且可以通过平面闪烁成像清晰地检测乳腺肿瘤。因此，（99m）Tc-N4-酪氨酸可能是一种用于乳腺肿瘤诊断成像的有用放射性示踪剂。
