Rapid Imaging of Tumor Cell Death In Vivo Using the C2A Domain of Synaptotagmin-I.
J Nucl Med
; 58(6): 881-887, 2017 06.
Article
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| MEDLINE
| ID: mdl-28209913
ABSTRACT
Cell death is an important target for imaging the early response of tumors to treatment. We describe here the validation of a phosphatidylserine-binding agent for detecting tumor cell death in vivo based on the C2A domain of synaptotagmin-I. Methods:
The capability of near-infrared fluorophore-labeled and 99mTc- and 111In-labeled derivatives of C2Am for imaging tumor cell death, using planar near-infrared fluorescence imaging and SPECT, respectively, was evaluated in implanted and genetically engineered mouse models of lymphoma and in a human colorectal xenograft.Results:
The fluorophore-labeled C2Am derivative showed predominantly renal clearance and high specificity and sensitivity for detecting low levels of tumor cell death (2%-5%). There was a significant correlation (R > 0.9, P < 0.05) between fluorescently labeled C2Am binding and histologic markers of cell death, including cleaved caspase-3, whereas there was no such correlation with a site-directed mutant of C2Am (iC2Am) that does not bind phosphatidylserine. 99mTc-C2Am and 111In-C2Am also showed favorable biodistribution profiles, with predominantly renal clearance and low nonspecific retention in the liver and spleen at 24 h after probe administration. 99mTc-C2Am and 111In-C2Am generated tumor-to-muscle ratios in drug-treated tumors of 4.3× and 2.2×, respectively, at 2 h and 7.3× and 4.1×, respectively, at 24 h after administration.Conclusion:
Given the favorable biodistribution profile of 99mTc- and 111In-labeled C2Am, and their ability to produce rapid and cell death-specific image contrast, these agents have potential for clinical translation.Palabras clave
Texto completo:
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Apoptosis
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Tomografía de Emisión de Positrones
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Sinaptotagmina I
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Imagen Molecular
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Neoplasias Experimentales
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Nucl Med
Año:
2017
Tipo del documento:
Article