Development of [90Y]DOTA-conjugated bisphosphonate for treatment of painful bone metastases
Development of [90Y]DOTA-conjugated bisphosphonate for treatment of painful bone metastases
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DOI：
10.1016/j.nucmedbio.2008.11.007
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发表时间：
2009-02-01
影响因子：
3.1
通讯作者：
Saji, Hideo
中科院分区：
文献类型：
--
作者：
Ogawa, Kazuma;Kawashima, Hidekazu;Saji, Hideo
前言：基于双功能放射性药物的概念，我们以前已经开发了Re-186络合物偶联双膦酸类化合物，用于缓解骨转移疼痛，并证明了这些化合物的实用性。通过应用类似的概念，我们假设可以开发一种骨定向的Y-90标记的放射性药物。方法：本研究选择1，4，7，10-tetrazacyclododecane-1，4，7，10-tetraacetic酸(DOTA)作为螯合部位，并将DOTA与4-amino-1-hydroxybutylidene-1，1-bisphosphonate.偶联结果：在生物分布实验中，[Y-90]DOTA-HBP和[Y-90]柠檬酸在骨组织中快速蓄积和滞留。虽然[Y-90]柠檬酸在骨骼中的蓄积水平高于[Y-90]DOTA-HBP，但[Y-90]DOTA-HBP从血液和几乎所有软组织中的清除速度比[Y-90]柠檬酸要快得多。因此，[Y-90]DOTA-HBP的软组织与成骨细胞(靶器官)的估计吸收剂量比低于[Y-90]柠檬酸盐。结论：[Y-90]DOTA-HBP作为一种寻骨剂具有更好的生物分布特性，与[Y-90]柠檬酸盐相比，可减少不必要的辐射水平。由于DOTA配体不仅与Y-90形成稳定的络合物，而且还与Lu(Lu-177)、In(In-111)、Ga(Ga-67/68)、Gd(Gd)等形成稳定的络合物，因此DOTA-偶联双膦酸根与各种金属的络合物可作为转移性骨痛的缓解剂、骨闪烁成像和磁共振成像的试剂。(C)2009 Elsevier Inc.保留所有权利。
Introduction: Based on the concept of bifunctional radiopharmaceuticals, we have previously developed Re-186-complex-conjugated bisphosphonate analogs for palliation of painful bone metastases and have demonstrated the utility of these compounds. By applying a similar concept, we hypothesized that a bone-specific directed Y-90-labeled radiopharmaceutical could be developed.Methods: In this study, 1,4,7,10-tetrazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as the chelating site, and DOTA was conjugated with 4-amino-1-hydroxybutylidene-1,1-bisphosphonate. [Y-90]DOTA-complex-conjugated bisphosphonate ([Y-90]DOTA-HBP) was prepared by coordination with Y-90, and its biodistribution was studied in comparison to [Y-90]citrate.Results: In biodistribution experiments, [Y-90]DOTA-HBP and [Y-90]citrate rapidly accumulated and resided in the bone. Although [Y-90] citrate showed a higher level of accumulation in the bone than [Y-90]DOTA-HBP, the clearances of [Y-90]DOTA-HBP from the blood and from almost all soft tissues were much faster than those of [Y-90]citrate. As a result, the estimated absorbed dose ratios of soft tissues to osteogenic cells (target organ) of [Y-90]DOTA-HBP were lower than those of [Y-90]citrate.Conclusions: [Y-90]DOTA-HBP showed superior biodistribution characteristics as a bone-seeking agent and led to a decrease in the level of unnecessary radiation compared to [Y-90]citrate. Since the DOTA ligand forms a stable complex not only with Y-90 but also with lutetium (Lu-177), indium (In-111), gallium (Ga-67/68), gadolinium (Gd) and so on, complexes of DOTA-conjugated bisphosphonate with various metals could be useful as agents for palliation of metastatic bone pain, bone scintigraphy and magnetic resonance imaging. (c) 2009 Elsevier Inc. All rights reserved.