Theoretical calculations and simulations
of interaction of X-rays
with high-Z nanomoities for use in
cancer radiotherapy
Sara N. Lim, Anil K. Pradhan, Sultana N. Nahar
Biophysics Graduate Program
Chemical Physics Program
Department of Astronomy
X-Ray Machines
• How are medical X-rays produced?
• Roentgen X-ray tube:
Intensity
Cathode + Anode
Tungsten
Anode
Electrons
Peak
Voltage
KVp or MVp
Cathode
Bremsstrahlung
Radiation
X-ray Energy
Imaging devices: Low Energy ~100 KVp – Radiology, CATscanners, etc.
Radiation Therapy: High Energy – 6-15 MVp LINAC
X-Ray Interaction With High-Z (HZ) Matter:
Radiosensitization
• Compton scattering dominates at high energies,
photoionization at low energies
• Inner-shell ionization  Auger Effect
• Auger electron emission  localized cell killing
• HZ Nanovehicles embedded in (tumor) cells
• X-ray photoionization induces Auger cascades
Auger Radiation and Electron cascade
This leaves us with four vacancies in the M-shell that will continue this increasing
cascade of electron ejection throughout the atom
We now have 2
vacancies in the LThe two M-shell electrons can
shell that will be
emit two photons, which can
filled with M-shell
then knock out two more Melectrons
shell electrons
Incident
The vacancy
in electron
the
The
gets
photon hits
K shell is filled
with leaving a
ejected,
the K-shell
an L-shell electron,
vacancy
creating a new
vacancy
Electron absorbs the photon
The L-shell electron then
emits a Kα photon,
which can leave as
fluorescence, or knock
out another L-shell
electron
Inner Shell Ionization of HZ Atoms (Gold):
Auger Electron Ejections
=0.009keV
=0.053keV
=0.4kEv
=2.75keV
Incident photon
knocks out one Kshell electron
That leads to a chain
reaction, ejecting
more than 20 Auger
electrons
=13.5keV
=80.7keV
High-Z Radiosensitization
(Gold or Platinum Nanomoities)
•
X-ray beam propagates through body
•
Attenuated by tissue and radiosensitized tumor,
located at certain depth in the body
• Monte Carlo simulations using Geant4 performed,
calculating X-ray dose enhancement with respect to
low 100-250 keV and high MeV energy X-rays
Gold nanoparticle
embedded tissue
X-ray
beam
Simulated Water Phantom
High Energy MeV X-rays have far lower
absorption than low energy keV X-rays
M
L
scat.
K
P.E.
scat.
P.E.
X-ray absorption coefficients of
Platinum and H2O
• P.E. – Photoelectric absorption
or photoionization
• Scat. – Compton scattering
Spectra of X-ray devices 100 kVp to 6 MVp
• Maxima at ~1/3 kVp or MVp
• High energy LINACs used in radiation
therapy produce X-rays mostly at
high MeV energies with low P.E.
absorption coefficients
High vs. Low X-ray energies Conundrum
• Need high energies for greater penetration in
the body to reach the tumor
• Need low energies for greater absorption by
radiaosensitization with high-Z moities
• LINACS used in radiation therapy ensure
sufficient depth but inefficient for
radiosensitization
Photoionization, Auger decays and
malignant cell-killing therapeutics
Photoabsorption vs. Depth in water phantom
•
Investigate low energy source 160 KVp,
and high energy LINAC 6 MVp
•
Simulate tumor at depth of 10 cm in water
phantom, sensitized with Pt at two different
concentrations: 1.0 mg/g and 7.0 mg/g
•
P.E. absorption from low energy 160 kV
source is more than an order of magnitude
higher than the 6 MV source (LINAC) with
change in concentration
•
LINAC high energy X-rays are largely
Compton
scattered
instead
of
photoionization and Auger decays; not
much dependence on Pt concentration
160 kV
6 MV
Pt sensitized tumor at 10 cm
X-ray absorption with depth of
radiosensitized tumor and energy
Photoionization
Low energy
160 kV X-rays
have much
higher absorption
than high energy
6 MV X-rays
Total (photo + Scatt)
Dose Enhancement Factors (DEF):
X-ray Dose absorbed w and w/o Pt
X-ray dose deposition as a function depth, 7ug/ml Pt at 10 cm in water phantom
160 kV
6 MV
Integrated DEF over the entire tumor volume; decreases with incident X-ray energy
Single Cell Dose Enhancement Factors
In Gold (Au) and Gadolinium (Gd)
Dose Deposition per photon
(in single cell)
80 keV
5 MeV
What about bone?
• Bone
(calcium) absorption of Xrays is higher than water
(muscle, fat)
• How is radiosensitization
affected in tissue covered with
bone ?
• Radiation therapy of brain
tumors!
Nightmare Before Christmas. Henry Selick, Tim Burton, Michael McDowell,
Caroline Thompson. Walt Disney Studios, 1993.
Brain (+Skull) Dose Enhancement
At Low KeV and High MeV Energies
Normalized
X-ray dose
1 Joule
• Greater dose to skull (~ 2.5 X for 80 keV),
BUT! dose to normal brain HALVED
• Dose to sensitized tumor less but comparable
Conclusion and Follow On
• Efficient radiation therapy using high-Z
compounds requires low-energy X-rays
• Next talk by Sara Lim
-- In vitro and in vivo experiments
-- HZ radiosensitization with low energy (keV) and
high energy (MeV) X-rays