Page 107 - 2014 Printable Abstract Book
P. 107
(PS1-06) Relative biological effectiveness of internal cytoplasmic or nuclear exposure to Auger-electron
emitters. Pil M. Fredericia; Torsten Groesser, PhD; and Mikael Jensen, PhD
Technical University of Denmark, Roskilde, Denmark
Considerable efforts have been made in the past twenty years to develop Auger emitter-based
radiotherapy. However, all previous studies lack precise measurement of the relative biological
effectiveness (RBE), which may well have slowed the development of new therapeutic substances and
new clinical protocols. The aim of this study is to investigate the RBE of internal exposure to specific Auger-
electron emitters, compared to internal exposure of β-rays and external sparsely ionizing radiation such
as photons or X-rays. First experiments have been performed after setting up a microinjection facility
here at the Hevesy laboratory. We are now able to inject precisely Auger-electron emitters into the
cytoplasm or cell nucleus of human and rodent cells. Dose effect curves will be produced for foci formation
of phosphorylated histone H2X (γ-H2AX) and p53 binding protein No. 1 (53BP1). These results will be
compared to dose response curves obtained after internal β-ray exposure and external exposure to
photons or X-rays at the newly established beamline, which is part of the Center for Nuclear Technologies
at the Risø campus. To address the issue concerning the amount of radioactivity injected, the
radioisotopes will be bound by chelate groups to fluorescence labeled dextran. This will allow correlating
the injected amount with the fluorescence intensity readout. These dextrans are modified hydrophilic
polysaccharides. They are biologically inert and resistant to cleavage by most endogenous cellular
glycosidases, which ensures that the radioactive isotopes colocalize with the fluorescents signal. The
chosen dextran size prevents leakage of the radioisotope through the nuclear or plasma membrane and
allows a precise spatial exposure of the cellular targets. Dextran has been used in live cell imaging and in
microinjection studies and has been shown to be non-toxic for cells at the concentration used. Supported
by the Hevesy Laboratory.
(PS1-07) Radiation induced DNA damage by internal Auger electron cascade (Cs131) compared to
1
1
internal γ-radiation (Cs137) and external γ-radiation. PIl M. Fredericia ; Torsten Groesser, Ph.D ; Gregory
2
1
1
1
Severin, Ph.D ; Ulli Koester, Ph.D ; and Mikael Jensen, Prof, DTU Nutech, Roskilde, Denmark and Laue-
Langevin, Grenoble, France
2
The aim of this study is to compare the radiation induced damage done by the internal Auger-
electron emitter (Cs131) with that done by internalized Cs137 or external exposure to sparsely ionizing
radiation such as γ-rays. Auger emitters decay by internal conversion (IC) or electron capture (EC)
producing a cascade of Auger electrons (10-30 Auger electrons per decay). These electrons are so low in
energy that their range in tissue is in the order of μm. This means that if the decay happens nearby the
DNA, the Auger electrons can produce a cluster of complex DNA damage. These clusters of DNA damage
are much harder to repair for the cell and increase the probability of misrejoining. Therefore they are
believed to be much more harmful to the cell than dispersed DNA double strand breaks, which are
primarily produced by low LET radiation. Due to their small tissue range and the severe DNA damage
produced, Auger emitters may be able to kill only the target cell while sparing non-targeted cells. This
makes them a potential tool for radionuclide therapy. Cs131 is an Auger-electron emitter that, as other
alkali metals, is actively taken up by the cell and dispersed in the cytoplasm and cell nucleus. To study the
105 | P a g e
emitters. Pil M. Fredericia; Torsten Groesser, PhD; and Mikael Jensen, PhD
Technical University of Denmark, Roskilde, Denmark
Considerable efforts have been made in the past twenty years to develop Auger emitter-based
radiotherapy. However, all previous studies lack precise measurement of the relative biological
effectiveness (RBE), which may well have slowed the development of new therapeutic substances and
new clinical protocols. The aim of this study is to investigate the RBE of internal exposure to specific Auger-
electron emitters, compared to internal exposure of β-rays and external sparsely ionizing radiation such
as photons or X-rays. First experiments have been performed after setting up a microinjection facility
here at the Hevesy laboratory. We are now able to inject precisely Auger-electron emitters into the
cytoplasm or cell nucleus of human and rodent cells. Dose effect curves will be produced for foci formation
of phosphorylated histone H2X (γ-H2AX) and p53 binding protein No. 1 (53BP1). These results will be
compared to dose response curves obtained after internal β-ray exposure and external exposure to
photons or X-rays at the newly established beamline, which is part of the Center for Nuclear Technologies
at the Risø campus. To address the issue concerning the amount of radioactivity injected, the
radioisotopes will be bound by chelate groups to fluorescence labeled dextran. This will allow correlating
the injected amount with the fluorescence intensity readout. These dextrans are modified hydrophilic
polysaccharides. They are biologically inert and resistant to cleavage by most endogenous cellular
glycosidases, which ensures that the radioactive isotopes colocalize with the fluorescents signal. The
chosen dextran size prevents leakage of the radioisotope through the nuclear or plasma membrane and
allows a precise spatial exposure of the cellular targets. Dextran has been used in live cell imaging and in
microinjection studies and has been shown to be non-toxic for cells at the concentration used. Supported
by the Hevesy Laboratory.
(PS1-07) Radiation induced DNA damage by internal Auger electron cascade (Cs131) compared to
1
1
internal γ-radiation (Cs137) and external γ-radiation. PIl M. Fredericia ; Torsten Groesser, Ph.D ; Gregory
2
1
1
1
Severin, Ph.D ; Ulli Koester, Ph.D ; and Mikael Jensen, Prof, DTU Nutech, Roskilde, Denmark and Laue-
Langevin, Grenoble, France
2
The aim of this study is to compare the radiation induced damage done by the internal Auger-
electron emitter (Cs131) with that done by internalized Cs137 or external exposure to sparsely ionizing
radiation such as γ-rays. Auger emitters decay by internal conversion (IC) or electron capture (EC)
producing a cascade of Auger electrons (10-30 Auger electrons per decay). These electrons are so low in
energy that their range in tissue is in the order of μm. This means that if the decay happens nearby the
DNA, the Auger electrons can produce a cluster of complex DNA damage. These clusters of DNA damage
are much harder to repair for the cell and increase the probability of misrejoining. Therefore they are
believed to be much more harmful to the cell than dispersed DNA double strand breaks, which are
primarily produced by low LET radiation. Due to their small tissue range and the severe DNA damage
produced, Auger emitters may be able to kill only the target cell while sparing non-targeted cells. This
makes them a potential tool for radionuclide therapy. Cs131 is an Auger-electron emitter that, as other
alkali metals, is actively taken up by the cell and dispersed in the cytoplasm and cell nucleus. To study the
105 | P a g e
