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Review
. 2018 Mar 12;23(3):638.
doi: 10.3390/molecules23030638.

Recent Advances in Zirconium-89 Chelator Development

Nikunj B Bhatt  1 , Darpan N Pandya  2 , Thaddeus J Wadas  3
Affiliations
Review

Recent Advances in Zirconium-89 Chelator Development

Nikunj B Bhatt et al. Molecules. .

Abstract

The interest in zirconium-89 (89Zr) as a positron-emitting radionuclide has grown considerably over the last decade due to its standardized production, long half-life of 78.2 h, favorable decay characteristics for positron emission tomography (PET) imaging and its successful use in a variety of clinical and preclinical applications. However, to be utilized effectively in PET applications it must be stably bound to a targeting ligand, and the most successfully used 89Zr chelator is desferrioxamine B (DFO), which is commercially available as the iron chelator Desferal®. Despite the prevalence of DFO in 89Zr-immuno-PET applications, the development of new ligands for this radiometal is an active area of research. This review focuses on recent advances in zirconium-89 chelation chemistry and will highlight the rapidly expanding ligand classes that are under investigation as DFO alternatives.

Keywords: chelator; positron emission tomography; zirconium-89.

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Conflict of interest statement

N.B.B., D.N.P. and T.J.W. have filed patents relating to work described in this text.

Figures

Figure 1
Figure 1
Zirconium-89 decay scheme. Zirconium-89 decays by positron emission and electron capture to metastable yttrium-89. Metastable yttrium-89 decays by gamma emission to stable yttrium-89.
Figure 2
Figure 2
DFO-based bifunctional chelators for 89Zr. The coordinating units are depicted in red font.
Figure 3
Figure 3
Selected bioconjugation reactions used to link 89Zr-bifunctional chelators A with targeting ligands B that are described in this text. For clarity, leaving groups and reaction conditions are not shown.
Figure 4
Figure 4
Hydroxamate-containing Zirconium-89 chelators inspired by the siderophores fusarine C and desferrichrome. The coordinating units are depicted in red font.
Figure 5
Figure 5
Macrocycle-based hydroxamate chelators for Zirconium-89. The coordinating units are depicted in red font.
Figure 6
Figure 6
Octa-coordinate chelators for 89Zr inspired by DFO. The coordinating units are depicted in red font.
Figure 7
Figure 7
Cyclen-and cyclam-based 89Zr chelators containing hydroxamate pendant arms. The coordinating units are depicted in red font.
Figure 8
Figure 8
Bifunctional chelators for 89Zr containing hydroxyisopthalamide and terepthalamide coordinating units. The coordinating units are depicted in red font.
Figure 9
Figure 9
Zirconium-89 chelators containing 3,4-hydroxypyridinone coordinating units. The coordinating units are depicted in red font.
Figure 10
Figure 10
Zirconium-89 chelators containing 2,3-hydroxypyridinone and 1,2-hydroxypyridinone coordinating units. The coordinating units are depicted in red font.
Figure 11
Figure 11
Zirconium-89 chelators containing tetraazamacrocycles. The coordinating units are depicted in red font.
See this image and copyright information in PMC

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