PMID- 32661612
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240329
IS  - 2191-219X (Print)
IS  - 2191-219X (Electronic)
IS  - 2191-219X (Linking)
VI  - 10
IP  - 1
DP  - 2020 Jul 13
TI  - Radiobiological and dosimetric assessment of DNA-intercalated (99m)Tc-complexes 
      bearing acridine orange derivatives.
PG  - 79
LID - 10.1186/s13550-020-00663-9 [doi]
LID - 79
AB  - BACKGROUND: Recently, a new family of (99m)Tc(I)-tricarbonyl complexes bearing an 
      acridine orange (AO) DNA targeting unit and different linkers between the Auger 
      emitter ((99m)Tc) and the AO moiety was evaluated for Auger therapy. Among them, 
      (99m)Tc-C(3) places the corresponding radionuclide at a shortest distance to DNA 
      and produces important double strand breaks (DSB) yields in plasmid DNA providing 
      the first evidence that (99m)Tc can efficiently induce DNA damage when well 
      positioned to the double helix. Here in, we have extended the studies to human 
      prostate cancer PC3 cells using the (99m)Tc-C(3) and (99m)Tc-C(5) complexes, 
      aiming to assess how the distance to DNA influences the radiation-induced 
      biological effects in this tumoral cell line, namely, in which concerns early and 
      late damage effects. RESULTS: Our results highlight the limited biological 
      effectiveness of Auger electrons, as short path length radiation, with increasing 
      distances to DNA. The evaluation of the radiation-induced biological effects was 
      complemented with a comparative microdosimetric study based on intracellular dose 
      values. The comparative study, between MIRD and Monte Carlo (MC) methods used to 
      assess the cellular doses, revealed that efforts should be made in order to 
      standardize the bioeffects modeling for DNA-incorporated Auger electron emitters. 
      CONCLUSIONS: (99m)Tc might not be the ideal radionuclide for Auger therapy but 
      can be useful to validate the design of new classes of Auger-electron emitting 
      radioconjugates. In this context, our results highlight the crucial importance of 
      the distance of Auger electron emitters to the target DNA and encourage the 
      development of strategies for the fine tuning of the distance to DNA for other 
      medical radionuclides (e.g., (111)In or (161)Tb) in order to enhance their 
      radiotherapeutic effects within the Auger therapy of cancer.
FAU - Belchior, Ana
AU  - Belchior A
AUID- ORCID: 0000-0002-6010-0316
AD  - Centro de Ciencias e Tecnologias Nucleares, Instituto Superior Tecnico, 
      Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066, Bobadela LRS, 
      Portugal. anabelchior@tecnico.ulisboa.pt.
FAU - Di Maria, Salvatore
AU  - Di Maria S
AD  - Centro de Ciencias e Tecnologias Nucleares, Instituto Superior Tecnico, 
      Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066, Bobadela LRS, 
      Portugal.
FAU - Fernandes, Celia
AU  - Fernandes C
AD  - Centro de Ciencias e Tecnologias Nucleares, Instituto Superior Tecnico, 
      Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066, Bobadela LRS, 
      Portugal.
FAU - Vaz, Pedro
AU  - Vaz P
AD  - Centro de Ciencias e Tecnologias Nucleares, Instituto Superior Tecnico, 
      Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066, Bobadela LRS, 
      Portugal.
FAU - Paulo, Antonio
AU  - Paulo A
AD  - Centro de Ciencias e Tecnologias Nucleares, Instituto Superior Tecnico, 
      Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066, Bobadela LRS, 
      Portugal.
FAU - Raposinho, Paula
AU  - Raposinho P
AD  - Centro de Ciencias e Tecnologias Nucleares, Instituto Superior Tecnico, 
      Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066, Bobadela LRS, 
      Portugal. paular@ctn.tecnico.ulisboa.pt.
LA  - eng
PT  - Journal Article
DEP - 20200713
PL  - Germany
TA  - EJNMMI Res
JT  - EJNMMI research
JID - 101560946
PMC - PMC7359215
OTO - NOTNLM
OT  - Auger emitters
OT  - DNA intercalators
OT  - Radiopharmaceuticals
OT  - Targeted radiotherapy
OT  - Technetium-99m
COIS- There is no competing interest.
EDAT- 2020/07/15 06:00
MHDA- 2020/07/15 06:01
PMCR- 2020/07/13
CRDT- 2020/07/15 06:00
PHST- 2020/01/22 00:00 [received]
PHST- 2020/06/25 00:00 [accepted]
PHST- 2020/07/15 06:00 [entrez]
PHST- 2020/07/15 06:00 [pubmed]
PHST- 2020/07/15 06:01 [medline]
PHST- 2020/07/13 00:00 [pmc-release]
AID - 10.1186/s13550-020-00663-9 [pii]
AID - 663 [pii]
AID - 10.1186/s13550-020-00663-9 [doi]
PST - epublish
SO  - EJNMMI Res. 2020 Jul 13;10(1):79. doi: 10.1186/s13550-020-00663-9.