Furin-Guided Intracellular 68Ga Nanoparticle Formation Enhancing Tumor MicroPET Imaging.
Anal Chem
; 91(23): 14842-14845, 2019 12 03.
Article
en En
| MEDLINE
| ID: mdl-31718142
ABSTRACT
Positron-emission tomography (PET) is routinely used in the clinic for tumor imaging with ultrahigh sensitivity, but tumor-targeted PET imaging probes are quite few. In this work, we rationally designed a furin-responsive radiotracer Acetyl-Arg-Val-Arg-Arg-Cys(StBu)-Lys(DOTA-68Ga)-CBT (CBT-68Ga) and demonstrated that coinjection of the radiotracer with its cold analogue CBT-Ga instructed the formation of 68Ga nanoparticles in furin-overexpressing MDA-MB-468 cancer cells, which significantly enhanced microPET imaging of the tumor in vivo. In vitro results showed that CBT-Ga subjected to furin-initiated CBT-Cys condensation reaction and self-assembly to form the nanoparticles CBT-Ga-NPs with an average diameter of 258.3 nm. In vivo microPET imaging results indicate that the mice coinjected with CBT-68Ga and CBT-Ga, which warrants 68Ga nanoparticle formation in their MDA-MB-468 tumors, had a tumor/liver ratio 9.1-fold of that of the mice only injected with CBT-68Ga. We envisioned that, by replacing the RVRR substrate of CBT-68Ga with other enzyme-specific ones and using the strategy of intracellular nanoparticle formation, a series of radioactive probes could be developed for more sensitive and precise tumor microPET imaging in the near future.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
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Biomarcadores de Tumor
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Radiofármacos
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Furina
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Tomografía de Emisión de Positrones
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Radioisótopos de Galio
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Anal Chem
Año:
2019
Tipo del documento:
Article
País de afiliación:
China