Synthesis and evaluation of 18F labeled alanine derivatives as potential tumor imaging agents.
Synthesis and evaluation of 18F labeled alanine derivatives as potential tumor imaging agents.
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DOI：
10.1016/j.nucmedbio.2012.03.007
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发表时间：
2012-10
影响因子：
3.1
通讯作者：
Kung HF
中科院分区：
文献类型：
--
作者：
Wang L;Zha Z;Qu W;Qiao H;Lieberman BP;Plössl K;Kung HF
本文报道了18F丙氨酸衍生物的合成和标记。我们还研究了它们作为潜在的肿瘤显像剂的生物学特性，这些肿瘤显像剂由丙氨酸-丝氨酸-半胱氨酸优先转运体系统（ASC）介导。通过两步标记反应，从相应的甲苯磺酸盐前体制备了三种新的18F丙氨酸衍生物。在9 L神经胶质瘤和PC-3前列腺癌细胞系中进行体外摄取研究以评估和比较这三种类似物。研究了3-（1-[18 F]氟甲基）-L-丙氨酸（L[18 F]FMA）在9 L胶质瘤细胞中的转运机制、蛋白掺入和稳定性。在大鼠荷9 L肿瘤模型中测定其生物分布。对携带9 L胶质瘤的大鼠和携带自发产生的M/tomND肿瘤（乳腺腺癌）的转基因小鼠进行PET成像研究。以7-34%的未校正放化产率、优异的对映体纯度（>99%）和良好的放化纯度（>99%）制备了新的18F丙氨酸衍生物。在9 L胶质瘤和PC-3前列腺癌细胞中，L-[18 F]FMA的体外摄取在前1小时高于其他两种丙氨酸衍生物和[18 F]FDG的体外摄取。细胞摄取抑制研究表明，9 L胶质瘤中L-[18 F]FMA摄取主要通过转运系统ASC进行。L-[18F]FMA进入细胞后保持稳定，在2 h内不掺入蛋白质中。体内生物分布研究表明，L-[18 F]FMA在肝脏和肾脏中的摄取相对较高。肿瘤摄取迅速，在30分钟内达到最大值。注射后60分钟的肿瘤与肌肉、肿瘤与血液和肿瘤与脑的比值分别为2.2、1.9和3.0。在PET成像研究中，用L-[18 F]FMA在9 L大鼠和转基因小鼠中观察肿瘤。L-[18 F]FMA显示出作为PET成像剂的有希望的特性，用于与肿瘤增殖相关的上调的ASC转运蛋白。
This paper reports the synthesis and labeling of 18F alanine derivatives. We also investigate their biological characteristics as potential tumor imaging agents mediated by alanine-serine-cysteine preferring (ASC) transporter system. Three new 18F alanine derivatives were prepared from corresponding tosylate-precursors through a two-step labelling reaction. In vitro uptake studies to evaluate and to compare these three analogs were carried out in 9L glioma and PC-3 prostate cancer cell lines. Potential transport mechanisms, protein incorporation and stability of 3-(1-[18F]fluoromethyl)-L-alanine (L[18F]FMA) were investigated in 9L glioma cells. Its biodistribution was determined in a rat-bearing 9L tumor model. PET imaging studies were performed on rat bearing 9L glioma tumors and transgenic mouse carrying spontaneous generated M/tomND tumor (mammary gland adenocarcinoma). New 18F alanine derivatives were prepared with 7–34% uncorrected radiochemical yields, excellent enantiomeric purity (>99%) and good radiochemical purity (>99%). In vitro uptake of the L-[18F]FMA in 9L glioma and PC-3 prostate cancer cells was higher than those observed for other two alanine derivatives and [18F]FDG in first 1 h. Inhibition of cell uptake studies suggested that L-[18F]FMA uptake in 9L glioma was predominantly via transport system ASC. After entering into cells, L-[18F]FMA remained stable and was not incorporated into protein within 2 h. In vivo biodistribution studies demonstrated that L-[18F]FMA had relatively high uptake in liver and kidney. Tumor uptake was fast, reaching a maximum within 30 min. The tumor-to-muscle, tumor-to-blood and tumor-to-brain ratios at 60 min post injection were 2.2, 1.9 and 3.0, respectively. In PET imaging studies, tumors were visualized with L-[18F]FMA in both 9L rat and transgenic mouse. L-[18F]FMA showed promising properties as a PET imaging agent for up-regulated ASC transporter associated with tumor proliferation.
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影响因子：
15
作者：
Qu, Wenchao;Zha, Zhihao;Kung, Hank F.
通讯作者：
Kung, Hank F.
影响因子：
5.5
作者：
Fuchs, Bryan C.;Finger, Richard E.;Bode, Barrie P.
通讯作者：
Bode, Barrie P.
影响因子：
2.2
作者：
Sakata, Takeshi;Ferdous, Golam;Okayasu, Isao
通讯作者：
Okayasu, Isao
影响因子：
3.1
作者：
Bauwens, Matthias;Lahoutte, Tony;Meltens, John
通讯作者：
Meltens, John
影响因子：
2
作者：
Schoenherr, Regine M.;Kelly-Spratt, Karen S.;Lin, ChenWei;Whiteaker, Jeffrey R.;Liu, Tao;Holzman, Ted;Coleman, Ilsa;Feng, Li-Chia;Lorentzen, Travis D.;Krasnoselsky, Alexei L.;Wang, Pei;Liu, Yan;Gurley, Kay E.;Amon, Lynn M.;Schepmoes, Athena A.;Moore, Ronald J.;Camp, David G., II;Chodosh, Lewis A.;Smith, Richard D.;Nelson, Peter S.;McIntosh, Martin W.;Kemp, Christopher J.;Paulovich, Amanda G.
通讯作者：
Paulovich, Amanda G.