QIMR Berghofer

Modification of Biodistribution and Brain Uptake of Copper Bis(thiosemicarbazonato) Complexes by the Incorporation of Amine and Polyamine Functional Groups


The synthesis of new bis(thiosemicarbazonato)copper(II) complexes featuring poly-amine substituents via selective transamination reactions is presented. Polyamines of different lengths, with different ionizable substituent groups, were used to modify and adjust the hydrophilic/lipophilic balance of the copper complexes. The new analogues were radiolabeled with copper-64 and their lipophilicities estimated using distribution coefficients. The cell uptake of the new polyamine complexes was investigated with preliminary in vitro biological studies using a neuroblastoma cancer cell line. The in vivo biodistribution of three of the new analogues was investigated in vivo in mice using positron-emission tomography imaging, and one of the new complexes was compared to [Cu-64]Cu(atsm) in an A431 squamous cell carcinoma xenograft model. Modification of the copper complexes with various amine-containing functional groups alters the biodistribution of the complexes in mice. One complex, with a pendent (N,N-dimethylamino)ethane functional group, displayed tumor uptake similar to that of [Cu-64]Cu(atsm) but higher brain uptake, suggesting that this compound has the potential to be of use in the diagnostic brain imaging of tumors and neurodegenerative diseases.

Authors Paterson, Brett M.; Cullinane, Carleen; Crouch, Peter J.; White, Anthony R.; Barnham, Kevin J.; Rose, Peter D.; Noonan, Wayne; Binns, David; Hicks, Rodney J.; Donnelly, Paul S.
Journal Inorganic Chemistry
Pages 4540-4552
Volume 58
Date 1/04/2019
Grant ID
Funding Body Australian Research Council
URL http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1021/acs.inorgchem.9b00117
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