Sgc8-c Aptamer as a Potential Theranostic Agent for Hemato-Oncological Malignancies

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Título

Sgc8-c Aptamer as a Potential Theranostic Agent for Hemato-Oncological Malignancies

Tema

LINFOMA
NEOPLASIAS
HEMATOLOGIA
ONCOLOGIA
BIBLIOGRAFIA NACIONAL QUIMICA
2020

Abstract

Background: Aptamers represent an emerging class of oligonucleotides that have the ability to bind ligands with high affinity. Sgc8-c aptamer recognizes PTK7, a member of the catalytically defective receptor protein tyrosine kinase family that is upregulated in various cancers, including hemato-oncological malignancies. Herein, an Sgc8-c-NOTA-radiolabeled probe was prepared for theranostic purpose. Materials and Methods: In this work, an Sgc8-c-radiolabeled probe against PTK7 was prepared, and biological evaluations—pharmacokinetic studies, biodistribution analysis, and in vivo molecular imaging—were performed. To obtain the radiolabeled probe, a modified 5′-amino-derivative of the Sgc8-c aptamer was bound to the metal chelator NOTA, and subsequently labeled with 67Ga with high yield and radiochemical purity. The precursor, Sgc8-c-NOTA, the radio probe Sgc8-c-NOTA-67Ga, and its nonradioactive complex, Sgc8-c-NOTA-69/71Ga, were purified by reverse-phase high-performance liquid chromatography and characterized by electrospray ionization mass spectrometry. The binding ability of Sgc8-c-NOTA-67Ga was studied in vitro against purified PTK7 receptor. In addition, the binding was also evidenced against the hemato-oncological A20 cell line, derived from B lymphocytes, and the corresponding A20-green fluorescent protein (GFP)-transfected cells. The proof of concept was performed on A20-GFP tumor-bearing mice, in which the biodistribution of the radiolabeled probe was evaluated through imaging, using X-ray, fluorescence, and γ modalities. The specific uptake of the probe was confirmed by blocking with the Sgc8-c aptamer in an in vivo competition assay. Results: The biodistribution results showed considerable uptake in tumor since 2 h, with highest at 48 h postinjection. However, the blood and muscle ID/g (injected dose per gram of tissue) activities were decreasing with time and tumor/no-target ratios increasing to 20 at 24 h postinjection. These results are consistent with the in vivo images. Conclusions: This study supports the utility of Sgc8-c-NOTA radiolabeled as a theranostic agent.

Autor

Sicco, Estefanía
Baez, Jessica
Ibarra, Manuel
Fernández, Marcelo
Cabral, Pablo
Moreno, María
Cerecetto, Hugo
Calzada, Victoria

Fuente

Cancer Biotheraphy and Radiopharmaceuticals v. 35,no. 4, 2020. -- p. 262-270

Editor

Mary Ann Liebert

Fecha

2020

Derechos

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PDF

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Inglés

Tipo

Artículo

Identificador

DOI: 10.1089/cbr.2019.3402

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Original Format

PDF
Fecha de agregación
July 1, 2020
Colección
Bibliografía Nacional Química
Tipo de Elemento
Document
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Citación
Sicco, Estefanía, “Sgc8-c Aptamer as a Potential Theranostic Agent for Hemato-Oncological Malignancies,” RIQUIM - Repositorio Institucional de la Facultad de Química - UdelaR, accessed August 12, 2020, http://riquim.fq.edu.uy/items/show/6103.
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