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.