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Publication details

Document type
Journal articles

Document subtype
Full paper

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

Participants in the publication
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)

Summary
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.

Date of Publication
2022-06-29

Where published
International Journal of Molecular Sciences

Publication Identifiers
ISSN - 1422-0067

Publisher
MDPI AG

Volume
23
Number
13

Starting page
7238

Document Identifiers
DOI - https://doi.org/10.3390/ijms23137238
URL - http://dx.doi.org/10.3390/ijms23137238


Export

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 }