Date of Degree


Document Type


Degree Name





Lynn C. Francesconi

Subject Categories



Bifunctional Chelator; DFO; HOPO; Ligands; Positron Emission Tomography; Zirconium-89


Antibodies are attractive targeting vectors for positron emission tomography (PET) based imaging agents due to their high affinity and selectivity to a variety of biological targets. Creating such imaging agents requires a radionuclide with suitable decay characteristics. This role has been filled by zirconium-89 which has a 78.41 h half-life that ideally matches the multi-day biological half-life of IgG antibodies.

However, the use of a radiometal necessitates the use of a bifunctional chelator to bind the metal and conjugate to the antibody. For 89Zr this has been the purview of various derivatives of desferrioxamine B (DFO); however, the observed uptake of radioactivity in the bones of mice is evidence of in vivo release of 89Zr4+. A more robust chelator designed specifically around the chemistry of Zr4+ could eliminate the release of the bone-seeking 89Zr4+ cation in vivo and thus make for a safer, more effective PET tracer with reduced dose to non-target tissues.

The investigation of alternative ligands will be described with an emphasis on the lead compound: a hydroxypyridinone based chelator -- 3,4,3-(LI-1,2-HOPO) or HOPO. The evaluation of the chelator itself will be detailed leading to the development of a bifunctional derivative -- p-SCN-Bn-HOPO -- that can be applied within the world of PET imaging.

Included in

Chemistry Commons



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