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Detalhes Referência

Tipo
Artigos em Revista

Tipo de Documento
Artigo Completo

Título
Searching for a Paradigm Shift in Auger-Electron Cancer Therapy with Tumor-Specific Radiopeptides Targeting the Mitochondria and/or the Cell Nucleus

Participantes na publicação
Célia Fernandes (Author)
Elisa Palma (Author)
Francisco Silva (Author)
Ana Belchior (Author)
Catarina I. G. Pinto (Author)
Joana F. Guerreiro (Author)
Hugo M. Botelho (Author)
Dep. Química e Bioquímica
 BioISI
 Filipa Mendes (Author)
Paula Raposinho (Author)
António Paulo (Author)

Resumo
Although 99mTc is not an ideal Auger electron (AE) emitter for Targeted Radionuclide Therapy (TRT) due to its relatively low Auger electron yield, it can be considered a readily available “model” radionuclide useful to validate the design of new classes of AE-emitting radioconjugates. With this in mind, we performed a detailed study of the radiobiological effects and mechanisms of cell death induced by the dual-targeted radioconjugates 99mTc-TPP-BBN and 99mTc-AO-BBN (TPP = triphenylphosphonium; AO = acridine orange; BBN = bombesin derivative) in human prostate cancer PC3 cells. 99mTc-TPP-BBN and 99mTc-AO-BBN caused a remarkably high reduction of the survival of PC3 cells when compared with the single-targeted congener 99mTc-BBN, leading to an augmented formation of γH2AX foci and micronuclei. 99mTc-TPP-BBN also caused a reduction of the mtDNA copy number, although it enhanced the ATP production by PC3 cells. These differences can be attributed to the augmented uptake of 99mTc-TPP-BBN in the mitochondria and enhanced uptake of 99mTc-AO-BBN in the nucleus, allowing the irradiation of these radiosensitive organelles with the short path-length AEs emitted by 99mTc. In particular, the results obtained for 99mTc-TPP-BBN reinforce the relevance of targeting the mitochondria to promote stronger radiobiological effects by AE-emitting radioconjugates.

Data de Publicação
2022-06-29

Suporte
International Journal of Molecular Sciences

Identificadores da Publicação
ISSN - 1422-0067

Editora
MDPI AG

Volume
23
Fascículo
13

Página Inicial
7238

Identificadores do Documento
DOI - https://doi.org/10.3390/ijms23137238
URL - http://dx.doi.org/10.3390/ijms23137238


Exportar referência

APA
Célia Fernandes, Elisa Palma, Francisco Silva, Ana Belchior, Catarina I. G. Pinto, Joana F. Guerreiro, Hugo M. Botelho, Filipa Mendes, Paula Raposinho, António Paulo, (2022). Searching for a Paradigm Shift in Auger-Electron Cancer Therapy with Tumor-Specific Radiopeptides Targeting the Mitochondria and/or the Cell Nucleus. International Journal of Molecular Sciences, 23, ISSN 1422-0067. eISSN . http://dx.doi.org/10.3390/ijms23137238

IEEE
Célia Fernandes, Elisa Palma, Francisco Silva, Ana Belchior, Catarina I. G. Pinto, Joana F. Guerreiro, Hugo M. Botelho, Filipa Mendes, Paula Raposinho, António Paulo, "Searching for a Paradigm Shift in Auger-Electron Cancer Therapy with Tumor-Specific Radiopeptides Targeting the Mitochondria and/or the Cell Nucleus" in International Journal of Molecular Sciences, vol. 23, 2022. 10.3390/ijms23137238

BIBTEX
@article{55800, author = {Célia Fernandes and Elisa Palma and Francisco Silva and Ana Belchior and Catarina I. G. Pinto and Joana F. Guerreiro and Hugo M. Botelho and Filipa Mendes and Paula Raposinho and António Paulo}, title = {Searching for a Paradigm Shift in Auger-Electron Cancer Therapy with Tumor-Specific Radiopeptides Targeting the Mitochondria and/or the Cell Nucleus}, journal = {International Journal of Molecular Sciences}, year = 2022, volume = 23 }