Alternative Chelator for 89Zr Radiopharmaceuticals: Radiolabeling and Evaluation of 3,4,3-(LI-1,2-HOPO)

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• 作者：Melissa A. Deri ; Shashikanth Ponnala ; Brian M. Zeglis ; Gabor Pohl ; J. J. Dannenberg ; Jason S. Lewis ; Lynn C. Francesconi
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：June 12, 2014
• 年：2014
• 卷：57
• 期：11
• 页码：4849-4860
• 全文大小：508K
• 年卷期：v.57,no.11(June 12, 2014)
• ISSN：1520-4804

文摘

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.