Abstract
LISTENWhat’s ‘HOT’ about Zirconium?
One of the leading diagnostic tools in clinical Nuclear Medicine is Positron Emission Tomography (PET). When a positron is emitted by a radionuclide, it travels a minute distance before colliding with an electron. These particles annihilate, releasing two simultaneous 511 keV gamma rays which travel in opposite directions. These concurrent gamma rays are detected by rings of scintillation detectors which make up the PET scanner. The equipment extrapolates back these pairs of gamma rays to create a three-dimensional image of the distribution of the radiopharmaceutical in the body.
Zirconium-89 is a radioactive isotope with a half-life of 78.41 hours which emits a positively charged beta particle or positron. 89Zr is being investigated as a non-standard PET isotope because its half-life is ideally matched to the circulation time of IgG antibodies which are highly specific disease-targeting moieties. Bifunctional chelates have to be incorporated onto IgG’s so that radiometals, such as Zr, can be covalently bound to the protein. The current method for chelating 89Zr uses the ligand desferrioxamine B (DFO). Molecular modeling suggests that DFO binds 89Zr through six oxygen atoms with two water molecules also coordinating the metal. There is, however, some evidence of release of 89Zr from DFO in vivo.
In order to minimize the release of free 89Zr in the body we aim to explore alternative ligand designs with a focus on octadentate ligands. Work has begun towards synthesizing both an established hydroxypyridinone (HOPO) ligand as well as a novel catechol ligand for studies with 89Zr.
What’s ‘HOT’ about Zirconium?
One of the leading diagnostic tools in clinical Nuclear Medicine is Positron Emission Tomography (PET). When a positron is emitted by a radionuclide, it travels a minute distance before colliding with an electron. These particles annihilate, releasing two simultaneous 511 keV gamma rays which travel in opposite directions. These concurrent gamma rays are detected by rings of scintillation detectors which make up the PET scanner. The equipment extrapolates back these pairs of gamma rays to create a three-dimensional image of the distribution of the radiopharmaceutical in the body.
Zirconium-89 is a radioactive isotope with a half-life of 78.41 hours which emits a positively charged beta particle or positron. 89Zr is being investigated as a non-standard PET isotope because its half-life is ideally matched to the circulation time of IgG antibodies which are highly specific disease-targeting moieties. Bifunctional chelates have to be incorporated onto IgG’s so that radiometals, such as Zr, can be covalently bound to the protein. The current method for chelating 89Zr uses the ligand desferrioxamine B (DFO). Molecular modeling suggests that DFO binds 89Zr through six oxygen atoms with two water molecules also coordinating the metal. There is, however, some evidence of release of 89Zr from DFO in vivo.
In order to minimize the release of free 89Zr in the body we aim to explore alternative ligand designs with a focus on octadentate ligands. Work has begun towards synthesizing both an established hydroxypyridinone (HOPO) ligand as well as a novel catechol ligand for studies with 89Zr.
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