Medical Isotopes Research Center, Peking University, 38# Xueyuan Road, 100191, Beijing, China.
Amino Acids. 2010 Jun;39(1):111-20. doi: 10.1007/s00726-009-0382-0. Epub 2009 Nov 26.
In this study, we reported the preparation and evaluation of (177)Lu-DOTA-RGD2, (177)Lu-DOTA-Bz-RGD2 and (177)Lu-DTPA-Bz-RGD2 (RGD2 = Ec(RGDfK)) as a potential therapeutic radiotracers for the treatment of integrin alpha(v)beta(3)-positive tumors. The BALB/c nude mice bearing the U87MG human glioma xenografts were used to evaluate the biodistribution characteristics and excretion kinetics of (177)Lu-DOTA-RGD2, (177)Lu-DOTA-Bz-RGD2 and (177)Lu-DTPA-Bz-RGD2. It was found that there were no major differences in their lipophilicity and biodistribution characteristics, particularly at latter time points. A major advantage of using DTPA-Bz as the bifunctional chelator (BFC) was its high radiolabeling efficiency (fast and high yield radiolabeling) at room temperature. Using DOTA and DOTA-Bz as BFCs, the radiolabeling kinetics was slow, and heating at 100 degrees C and higher DOTA-conjugate concentration were needed for successful (177)Lu-labeling. Therefore, DTPA-Bz is an optimal BFC for routine preparation of (177)Lu-labeled cyclic RGDfK peptides, and (177)Lu-DTPA-Bz-RGD2 is worthy of further investigation for targeted radiotherapy of integrin alpha(v)beta(3)-positive tumors.
在这项研究中，我们报告了 (177)Lu-DOTA-RGD2、(177)Lu-DOTA-Bz-RGD2 和 (177)Lu-DTPA-Bz-RGD2（RGD2=E[c(RGDfK)]（2））的制备和评价，作为治疗整合素 alpha(v)beta(3)阳性肿瘤的潜在治疗性放射性示踪剂。使用荷人 U87MG 神经胶质瘤异种移植瘤的 BALB/c 裸鼠评估了 (177)Lu-DOTA-RGD2、(177)Lu-DOTA-Bz-RGD2 和 (177)Lu-DTPA-Bz-RGD2 的生物分布特征和排泄动力学。结果发现，它们的亲脂性和生物分布特征没有明显差异，特别是在后期时间点。使用 DTPA-Bz 作为双功能螯合剂（BFC）的一个主要优点是，在室温下其具有高放射性标记效率（快速且高产量的放射性标记）。使用 DOTA 和 DOTA-Bz 作为 BFC 时，放射性标记动力学较慢，需要在 100 度及更高的 DOTA 缀合物浓度下加热才能成功进行 (177)Lu 标记。因此，DTPA-Bz 是常规制备 (177)Lu 标记环 RGDfK 肽的理想 BFC，(177)Lu-DTPA-Bz-RGD2 值得进一步研究，作为整合素 alpha(v)beta(3)阳性肿瘤的靶向放射治疗。
