Alternative chelator for ⁸⁹Zr radiopharmaceuticals: radiolabeling and evaluation of 3,4,3-(LI-1,2-HOPO).
Alternative chelator for ⁸⁹Zr radiopharmaceuticals: radiolabeling and evaluation of 3,4,3-(LI-1,2-HOPO).
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DOI：
10.1021/jm500389b
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发表时间：
2014-06-12
影响因子：
7.3
通讯作者：
Francesconi LC
中科院分区：
文献类型：
--
作者：
Deri MA;Ponnala S;Zeglis BM;Pohl G;Dannenberg JJ;Lewis JS;Francesconi LC
锆-89是用于基于抗体的正电子发射断层扫描（PET）成像的有效放射性核素，因为其物理半衰期（78.41小时）与IgG抗体的生物半衰期相匹配。去铁胺（DFO）目前是89 Zr 4+的首选螯合剂;然而，小鼠骨骼中89 Zr的蓄积表明89 Zr 4+在体内从DFO中释放。改进的89 Zr 4+螯合剂可以消除亲骨性89 Zr 4+的释放，并导致更安全的PET示踪剂，降低了背景辐射剂量。本文中，我们提出了一种八齿螯合剂3，4，3-（LI-1，2-HOPO）（或HOPO）作为DFO的潜在上级替代物。HOPO配体形成了1：1的Zr-HOPO配合物，实验和理论上进行了评估。在每个实验中，89 Zr-HOPO的稳定性匹配或超过89 Zr-DFO的稳定性。在健康小鼠中，89 Zr-HOPO迅速清除身体，没有脱金属的迹象。最终，HOPO有可能取代DFO，成为基于89 Zr的PET显像剂的首选螯合剂。
Zirconium-89 is an effective radionuclide for antibody-based positron emission tomography (PET) imaging because its physical half-life (78.41 h) matches the biological half-life of IgG antibodies. Desferrioxamine (DFO) is currently the preferred chelator for 89Zr4+; however, accumulation of 89Zr in the bones of mice suggests that 89Zr4+ is released from DFO in vivo. An improved chelator for 89Zr4+ could eliminate the release of osteophilic 89Zr4+ and lead to a safer PET tracer with reduced background radiation dose. Herein, we present an octadentate chelator 3,4,3-(LI-1,2-HOPO) (or HOPO) as a potentially superior alternative to DFO. The HOPO ligand formed a 1:1 Zr-HOPO complex that was evaluated experimentally and theoretically. The stability of 89Zr-HOPO matched or surpassed that of 89Zr-DFO in every experiment. In healthy mice, 89Zr-HOPO cleared the body rapidly with no signs of demetalation. Ultimately, HOPO has the potential to replace DFO as the chelator of choice for 89Zr-based PET imaging agents.
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影响因子：
3.1
作者：
Abou DS;Ku T;Smith-Jones PM
通讯作者：
Smith-Jones PM
影响因子：
4.6
作者：
GLEN, GL;HOARD, JL;SILVERTON, JV
通讯作者：
SILVERTON, JV
影响因子：
4.6
作者：
HOARD, JL;SILVERTON, JV
通讯作者：
SILVERTON, JV
影响因子：
9.3
作者：
Dijkers, Eli C. F.;Kosterink, Jos G. W.;Lub-de Hooge, Marjolijn N.
通讯作者：
Lub-de Hooge, Marjolijn N.
影响因子：
--
作者：
BONDI, A
通讯作者：
BONDI, A