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J Med Chem ; 58(10): 4348-56, 2015 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-25923454

RESUMO

Near-infrared (NIR) fluorescent contrast agents are emerging in optical imaging as sensitive, cost-effective, and nonharmful alternatives to current agents that emit harmful ionizing radiation. Developing spectrally distinct NIR fluorophores to visualize sensitive vital tissues to selectively avoid them during surgical resection of diseased tissue is of great significance. Herein, we report the synthetic variation of pentamethine cyanine fluorophores with modifications of physicochemical properties toward prompting tissue-specific uptake into sensitive tissues (i.e., endocrine glands). Tissue-specific targeting and biodistribution studies revealed localization of contrast agents in the adrenal and pituitary glands, pancreas, and lymph nodes with dependence on molecular characteristics. Incorporation of hydrophobic heterocyclic rings, alkyl groups, and halogens allowed a fine-tuning capability to the hydrophobic character and dipole moment for observing perturbation in biological activity in response to minor structural alterations. These NIR contrast agents have potential for clinical translation for intraoperative imaging in the delineation of delicate glands.


Assuntos
Meios de Contraste/química , Meios de Contraste/farmacocinética , Imagem Óptica/métodos , Animais , Técnicas de Química Sintética , Meios de Contraste/síntese química , Glândulas Endócrinas/efeitos dos fármacos , Feminino , Corantes Fluorescentes/química , Interações Hidrofóbicas e Hidrofílicas , Período Intraoperatório , Linfonodos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos , Espectrofotometria/métodos , Relação Estrutura-Atividade , Sus scrofa , Distribuição Tecidual
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