Modification of Biodistribution and Brain Uptake of Copper Bis(thiosemicarbazonato) Complexes by the Incorporation of Amine and Polyamine Functional Groups.
Inorg Chem
; 58(7): 4540-4552, 2019 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-30869878
ABSTRACT
The synthesis of new bis(thiosemicarbazonato)copper(II) complexes featuring polyamine 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 [64Cu]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 [64Cu]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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Poliaminas
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Tiossemicarbazonas
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Encéfalo
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Radioisótopos de Cobre
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Compostos Radiofarmacêuticos
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Complexos de Coordenação
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article