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Evaluation of the theranostic potential of [64Cu]CuCl2 in glioblastoma spheroids.
Pinto, Catarina I G; Branco, André D M; Bucar, Sara; Fonseca, Alexandra; Abrunhosa, Antero J; da Silva, Cláudia L; Guerreiro, Joana F; Mendes, Filipa.
Afiliación
  • Pinto CIG; C2TN - Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.
  • Branco ADM; Department of Bioengineering, iBB - Institute for Bioengineering and Biosciences, Associate Laboratory i4HB - Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.
  • Bucar S; Department of Bioengineering, iBB - Institute for Bioengineering and Biosciences, Associate Laboratory i4HB - Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.
  • Fonseca A; CIBIT/ICNAS Instituto de Ciências Nucleares Aplicadas à Saúde, Universidade de Coimbra, Coimbra, Portugal.
  • Abrunhosa AJ; ICNAS PHARMA, Universidade de Coimbra, Coimbra, Portugal.
  • da Silva CL; CIBIT/ICNAS Instituto de Ciências Nucleares Aplicadas à Saúde, Universidade de Coimbra, Coimbra, Portugal.
  • Guerreiro JF; ICNAS PHARMA, Universidade de Coimbra, Coimbra, Portugal.
  • Mendes F; Department of Bioengineering, iBB - Institute for Bioengineering and Biosciences, Associate Laboratory i4HB - Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.
EJNMMI Res ; 14(1): 26, 2024 Mar 07.
Article en En | MEDLINE | ID: mdl-38453813
ABSTRACT

BACKGROUND:

Glioblastoma is an extremely aggressive malignant tumor with a very poor prognosis. Due to the increased proliferation rate of glioblastoma, there is the development of hypoxic regions, characterized by an increased concentration of copper (Cu). Considering this, 64Cu has attracted attention as a possible theranostic radionuclide for glioblastoma. In particular, [64Cu]CuCl2 accumulates in glioblastoma, being considered a suitable agent for positron emission tomography. Here, we explore further the theranostic potential of [64Cu]CuCl2, by studying its therapeutic effects in advanced three-dimensional glioblastoma cellular models. First, we established spheroids from three glioblastoma (T98G, U373, and U87) and a non-tumoral astrocytic cell line. Then, we evaluated the therapeutic responses of spheroids to [64Cu]CuCl2 exposure by analyzing spheroids' growth, viability, and cells' proliferative capacity. Afterward, we studied possible mechanisms responsible for the therapeutic outcomes, including the uptake of 64Cu, the expression levels of a copper transporter (CTR1), the presence of a cancer stem cell population, and the production of reactive oxygen species (ROS).

RESULTS:

Results revealed that [64Cu]CuCl2 is able to significantly reduce spheroids' growth and viability, while also affecting cells' proliferation capacity. The uptake of 64Cu, the presence of cancer stem-like cells and the production of ROS were in accordance with the therapeutic response. However, expression levels of CTR1 were not in agreement with uptake levels, revealing that other mechanisms could be involved in the uptake of 64Cu.

CONCLUSIONS:

Overall, our results further support [64Cu]CuCl2 potential as a theranostic agent for glioblastoma, unveiling potential mechanisms that could be involved in the therapeutic response.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: EJNMMI Res Año: 2024 Tipo del documento: Article País de afiliación: Portugal Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: EJNMMI Res Año: 2024 Tipo del documento: Article País de afiliación: Portugal Pais de publicación: Alemania