Development of Nanodosimetry for Biomedical Applications

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Development of Nanodosimetry for Biomedical
Applications

• Project Goals and Current Status

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Project Participants
Loma Linda University (LLU) (Rad. Medicine)
Reinhard Schulte Vladimir Bashkirov George
Coutrakon Pete Koss
Weizmann Institute of Science (WIS) (Rad.
Detection Physics Lab.)
Amos Breskin Guy Garty Rachel Chechik Itzhak
Orion Sergei Shchemelinin
University of California at San Diego (UCSD)
(Radiobiology)
John F. Ward Jamie Milligan Joe Aguilera
University of California Santa Cruz (UCSD) (Santa
Cruz Institute of Particle Physics)
Abe Seiden Patrick Spradlin Hartmut
Sadrozinski Brian Keeney Wilko Kroeger
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What is Nanodosimetry?
A new experimental technique that measures energy
deposition by ionizing radiation in wall-less
low-pressure gas volumes equivalent to
tissue-equivalent volumes of nanometer size
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Radiation Damage to the DNA
Ionization event (formation of water radicals)
Light damage- reparable
Primary particle track
delta rays
e-
Water radicals attack the DNA
OH
Clustered damage- irreparable
The mean diffusion distance of OH radicals before
they react is only 2-3 nm
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What do we want to know?
To better understand DNA damage we want to know
how many ionization events occurred and where did
they occur.
Problem How can we measure the formation of ions
with nanometer precision?
Using conventional techniques - impossible We
can only measure ion formation with millimer
resolution
If we had millimeter DNA - no problem.
Solution We measure ionization patterns in
low-pressure gas
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Project Goals

• Establishment of a nanodosimetric gas model to
  simulate ionizations in DNA and associated water
• Plasmid-based DNA model to measure DNA damage
• Develop models to correlate nanodosimetric
  spectra with DNA damage

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Project Schedule
YEAR 4
3D tracking system
YEAR 3
ND characterization
YEAR 2
ND fabrication (2 versions)
YEAR 1
Ion counting nanodosimetry (proof of
principle) Plasmid assays
2001 2000 1999 1998
SV mapping
ND improvements 2 D particle tracking
ND spectra MC simulation
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ion counter
vacuum
E2 (strong)
d electron
ion
E1 (pulsed)
primary charged particle
low pressure gas
primary particle detector
Single-Charge Counting Dosimetry
low pressure gas
E3 (weak)
electron
Gas based electron multiplier
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Current Status of the Ion Counting ND

• Principle proven (1998)
• Two prototype of NDs have been built
• LLUMC ND adapted to the proton synchrotron beam
  line
• WIS ND adapted to the Pelletron beam line
• 2-D particle selection implemented
• Data Acquisition System
• first version successfully implemented
• new version under development

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Prototype Nanodosimeter
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Sensitive Volume Mapping
The sensitive volume of the ND is defined by the
relative ion collection efficiency map
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ND Ion Cluster Spectra
Event with 6 ions
A primary particle event is followed by an ion
trail registered by the ion counter (electron
multiplier) For low-LET irradiation, most events
are empty
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ND Ion Cluster Spectra
Ion cluster spectra depend on particle type and
energy as well as position of the primary
particle track The average cluster size increases
with increasing LET
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Radiobiological Model

• Plasmid (pHAZE)
• Irradiation of thin film of plasmid DNA in
  aqueous solution
• Three structural forms
• superhelical (no damage)
• open circle (single strand break)
• linear (double strand break)
• Separation by agarose gel electrophoresis
• Fluorescent staining and dedicated imaging system

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Correlation between Nanodosimetry and Radiobiology
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ND Data Acquisition(non-position sensitive)
In the prototype ND all primary particles can
contribute to the ion cluster size spectra The
position of the primary particles is undefined
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ND Data Acquisition(particle-position sensitive)
In this (newer) version the primary beam is
imaged by a MWPC Only particles that pass a
narrow collimator in front of the rear
scintillator/PMT are selected for analysis
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The Goal 3-D Position- and Energy-Sensitive
Particle Tracking System
interface board
primary particle
Y
X