PMID- 28211920
OWN - NLM
STAT- MEDLINE
DCOM- 20181030
LR  - 20190101
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
DP  - 2017 Feb 13
TI  - Evaluation of Acridine Orange Derivatives as DNA-Targeted Radiopharmaceuticals 
      for Auger Therapy: Influence of the Radionuclide and Distance to DNA.
PG  - 42544
LID - 10.1038/srep42544 [doi]
LID - 42544
AB  - A new family of (99m)Tc(I)- tricarbonyl complexes and (125)I-heteroaromatic 
      compounds bearing an acridine orange (AO) DNA targeting unit was evaluated for 
      Auger therapy. Characterization of the DNA interaction, performed with the 
      non-radioactive Re and (127)I congeners, confirmed that all compounds act as DNA 
      intercalators. Both classes of compounds induce double strand breaks (DSB) in 
      plasmid DNA but the extent of DNA damage is strongly dependent on the linker 
      between the Auger emitter ((99m)Tc or (125)I) and the AO moiety. The in vitro 
      evaluation was complemented with molecular docking studies and Monte Carlo 
      simulations of the energy deposited at the nanometric scale, which corroborated 
      the experimental data. Two of the tested compounds, (125)I-C(5) and (99m)Tc-C(3), 
      place the corresponding radionuclide at similar distances to DNA and produce 
      comparable DSB yields in plasmid and cellular DNA. These results provide the 
      first evidence that (99m)Tc can induce DNA damage with similar efficiency to that 
      of (125)I, when both are positioned at comparable distances to the double helix. 
      Furthermore, the high nuclear retention of (99m)Tc-C(3) in tumoral cells suggests 
      that (99m)Tc-labelled AO derivatives are more promising for the design of 
      Auger-emitting radiopharmaceuticals than the (125)I-labelled congeners.
FAU - Pereira, Edgar
AU  - Pereira E
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 - do Quental, Leticia
AU  - do Quental L
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 - Palma, Elisa
AU  - Palma E
AD  - Centro de Ciencias e Tecnologias Nucleares, Instituto Superior Tecnico, 
      Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, 
      Portugal.
AD  - Centro Quimica Estrutural, Instituto Superior Tecnico, Universidade de Lisboa, 
      Av. Rovisco Pais 1049-001 Lisboa, Portugal.
FAU - Oliveira, Maria Cristina
AU  - Oliveira MC
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 - Mendes, Filipa
AU  - Mendes F
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.
FAU - Correia, Isabel
AU  - Correia I
AD  - Centro Quimica Estrutural, Instituto Superior Tecnico, Universidade de Lisboa, 
      Av. Rovisco Pais 1049-001 Lisboa, Portugal.
FAU - Lavrado, Joao
AU  - Lavrado J
AD  - iMed.ULisboa, Faculdade de Farmacia, Universidade de Lisboa, Av. Prof. Gama 
      Pinto, 1649-003 Lisboa, Portugal.
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 - Belchior, Ana
AU  - Belchior 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 - 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 - Santos, Isabel
AU  - Santos I
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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170213
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Radiopharmaceuticals)
RN  - 7440-26-8 (Technetium)
RN  - 9007-49-2 (DNA)
RN  - F30N4O6XVV (Acridine Orange)
RN  - GVO776611R (Iodine-125)
SB  - IM
MH  - Acridine Orange/*analogs & derivatives/chemical synthesis/*chemistry/therapeutic 
      use
MH  - Cell Line, Tumor
MH  - Chromatography, High Pressure Liquid
MH  - DNA/*chemistry
MH  - DNA Damage
MH  - Drug Stability
MH  - Humans
MH  - Iodine Radioisotopes/chemistry/therapeutic use
MH  - Models, Molecular
MH  - Molecular Conformation
MH  - Molecular Docking Simulation
MH  - Molecular Dynamics Simulation
MH  - Molecular Structure
MH  - Monte Carlo Method
MH  - Radiopharmaceuticals/chemical synthesis/*chemistry/therapeutic use
MH  - Spectrum Analysis
MH  - Technetium/chemistry/therapeutic use
PMC - PMC5304164
COIS- The authors declare no competing financial interests.
EDAT- 2017/02/18 06:00
MHDA- 2018/10/31 06:00
PMCR- 2017/02/13
CRDT- 2017/02/18 06:00
PHST- 2016/10/25 00:00 [received]
PHST- 2017/01/09 00:00 [accepted]
PHST- 2017/02/18 06:00 [entrez]
PHST- 2017/02/18 06:00 [pubmed]
PHST- 2018/10/31 06:00 [medline]
PHST- 2017/02/13 00:00 [pmc-release]
AID - srep42544 [pii]
AID - 10.1038/srep42544 [doi]
PST - epublish
SO  - Sci Rep. 2017 Feb 13;7:42544. doi: 10.1038/srep42544.