Preliminary in vivo characterization of a theranostic aptamer: Sgc8-c- DOTA-67Ga

Calzada, Victoria - Báez, Jessica - Sicco, Estefanía - Margenat, Jimena - Fernández, Marcelo - Moreno, María - Ibarra, Manuel - Gambini, Juan Pablo - Cabral González, Pablo - Cerecetto, Hugo

Resumen:

Nucleic acid aptamers can recognise their target with high affinity and specificity, and their potential as molecular imaging agents and use in theranostics are being explored. Compared with antibodies, aptamers can be easily synthesized and chemically modified, rendering them a valuable tool for in vivo approaches. Herein, we investigated a 41nt DNA aptamer as a theranostic agent for lymphoma and melanoma. This aptamer exhibits specific binding and high affinity for the PTK7 receptor that is overexpressed in many cancer cells. A 5’-amino-derivative of the Sgc8-c aptamer was bound to the metal chelator DOTA (1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid) and labelled with the radionuclide 67Ga, forming the aptamer probe Sgc8- c-DOTA-67Ga. Different conditions during synthesis, purification and identification of the intermediate and final radiolabelled probe, were examined. Aptamer modification and radiolabelling were performed with high yields, resulting in a probe that was stable in neutral buffered solution. Binding to PTK7 was studied in CCRFCEM, A20 and B16F1 cell lines, and in purified PTK7-1 receptor, to confirm specificity. The in vitro cell lines showed different levels of uptake, and the signal increased over time. In vivo binding properties were studied in A20 and B16F10 tumour-bearing mice and images were acquired using X-rays and gamma imaging modalities for both models. Preliminary results in both tumour models showed good aptamer uptake by tumour. Hepatobiliar metabolism was observed with Sgc8-c-DOTA-67Ga and no signal was detected in normal tissue. In summary, these results support the utility of labelled aptamers as theranostic agents in different imaging modalities and theranostic.


Detalles Bibliográficos
2017
Aptamer
Sgc8-c
PTK7
Molecular imaging
Theranostic
Inglés
Universidad de la República
COLIBRI
https://hdl.handle.net/20.500.12008/24810
Acceso abierto
Licencia Creative Commons Atribución - No Comercial (CC - By-NC 4.0)
Resumen:
Sumario:Nucleic acid aptamers can recognise their target with high affinity and specificity, and their potential as molecular imaging agents and use in theranostics are being explored. Compared with antibodies, aptamers can be easily synthesized and chemically modified, rendering them a valuable tool for in vivo approaches. Herein, we investigated a 41nt DNA aptamer as a theranostic agent for lymphoma and melanoma. This aptamer exhibits specific binding and high affinity for the PTK7 receptor that is overexpressed in many cancer cells. A 5’-amino-derivative of the Sgc8-c aptamer was bound to the metal chelator DOTA (1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid) and labelled with the radionuclide 67Ga, forming the aptamer probe Sgc8- c-DOTA-67Ga. Different conditions during synthesis, purification and identification of the intermediate and final radiolabelled probe, were examined. Aptamer modification and radiolabelling were performed with high yields, resulting in a probe that was stable in neutral buffered solution. Binding to PTK7 was studied in CCRFCEM, A20 and B16F1 cell lines, and in purified PTK7-1 receptor, to confirm specificity. The in vitro cell lines showed different levels of uptake, and the signal increased over time. In vivo binding properties were studied in A20 and B16F10 tumour-bearing mice and images were acquired using X-rays and gamma imaging modalities for both models. Preliminary results in both tumour models showed good aptamer uptake by tumour. Hepatobiliar metabolism was observed with Sgc8-c-DOTA-67Ga and no signal was detected in normal tissue. In summary, these results support the utility of labelled aptamers as theranostic agents in different imaging modalities and theranostic.