@article {SOUTHCOTT2022111936,
	title = {Trastuzumab-conjugated oxine-based ligand for [89Zr]Zr4+ immunoPET},
	journal = {J. Inorg. Biochem.},
	volume = {235},
	year = {2022},
	month = {07/2022},
	pages = {111936. Invited for Special Issue: Celebrating 50 Years of the Journal of Inorganic Biochemistry},
	abstract = {<p>A new, bifunctional chelating ligand for immuno-Positron Emission Tomography (PET) was designed, synthesized, and conjugated to Trastuzumab for a proof-of-concept study with 89Zr. H4neunox was synthesized from the tris(2-aminoethyl)amine backbone, decorated with 8-hydroxyquinoline moieties, and utilizes a primary amine for functionalization. A maleimide moiety extends the chelator to create H4neunox-mal for antibody conjugation via maleimide-thiol click chemistry. Preliminary 89Zr radiolabeling of H4neunox indicated quantitative radiolabeling at 1 \&times; 10\&minus;5 M, but improved inertness towards human serum (96\% intact at 7 d) and Fe3+ (92\% intact at 24 h) compared to the previously synthesized H5decaox. The chelator was successfully conjugated to the monoclonal antibody, Trastuzumab, and used in preliminary radiolabeling reactions (37 \&deg;C, 2 h) with 89Zr. Radiochemical assessments of the new H4neunox-Trastuzumab conjugate include 89Zr radiolabeling, spin filter purification, cell-binding immunoreactivity, and in vivo PET imaging and biodistribution in SKOV-3 tumour bearing nude mice, performed in comparison with the desferrioxamine B analog, DFO-Trastuzumab. The [89Zr]Zr(neunox-Trastuzumab) showed lowered inertness towards serum (76\% intact at 24 h) as well as demetallation in vivo through bone uptake (21\% ID/g) in PET imaging and biodistribution studies when compared to [89Zr]Zr(DFO-Trastuzumab). Although the combination of the chelator and antibody had detrimental effects on their intended purposes, nonetheless, the primary amine platform of H4neunox developed here provides an oxine-based bifunctional ligand for further derivatizations with other targeting vectors.</p>},
	keywords = {89Zr, BIODISTRIBUTION, immunopet, Neunox, Oxine-ligand conjugate, Trastuzamab},
	issn = {0162-0134},
	doi = {https://doi.org/10.1016/j.jinorgbio.2022.111936},
	url = {https://www.sciencedirect.com/science/article/pii/S0162013422002252},
	author = {Lily Southcott and Luke Wharton and Julie Rousseau and Helen Merkens and Hua Yang and Fran{\c c}ois B{\'e}nard and Chris Orvig}
}
