Alternative chelator for (89)Zr radiopharmaceuticals: Radiolabeling and evaluation of 3,4,3-(LI-1,2-HOPO) Journal Article
| Authors: | Deri, M. A.; Ponnala, S.; Zeglis, B. M.; Pohl, G.; Dannenberg, J. J.; Lewis, J. S.; Francesconi, L. C. |
| Article Title: | Alternative chelator for (89)Zr radiopharmaceuticals: Radiolabeling and evaluation of 3,4,3-(LI-1,2-HOPO) |
| Abstract: | 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. © 2014 American Chemical Society. |
| Journal Title: | Journal of Medicinal Chemistry |
| Volume: | 57 |
| Issue: | 11 |
| ISSN: | 0022-2623 |
| Publisher: | American Chemical Society |
| Date Published: | 2014-06-01 |
| Start Page: | 4849 |
| End Page: | 4860 |
| Language: | English |
| DOI: | 10.1021/jm500389b |
| PROVIDER: | scopus |
| PMCID: | PMC4059252 |
| PUBMED: | 24814511 |
| DOI/URL: | |
| Notes: | J. Med. Chem. -- Export Date: 8 July 2014 -- CODEN: JMCMA -- Source: Scopus |
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