Biomedical Engineering Reference
In-Depth Information
witness the emergence of enormous social and corporate interest in both proton and
heavy ion therapy, resulting in the planning and construction of many public and
first commercial particle treatment centers.
The main advantage of ion therapy as compared to conventional radiation therapy
is its finite and energy-dependent penetration depth in biological tissue, leading
to the phenomenon of the so-called Bragg-peak. At the Bragg-peak, fast ions are
slowed down to MeV energies and below. Ion velocities become comparable to
velocities of molecular valence electrons and the energy deposition into the medium
maximizes. Furthermore, the biological effectiveness (RBE) is strongly enhanced.
Undesired effects of proton and heavy ion irradiation due to naturally occuring
solar particle events and galactic cosmic rays are one of the constraints on manned
space exploration. Even for heavy shielding, a trip to Mars would lead to an
additional risk of cancer of about 1% per year which may extend up to 5% per
year [
6
]. The August 1972 solar proton storm (in between two Apollo missions),
which lasted about 15 hours only would have exposed astronauts to a severe dose
of 1 Gy of radiation (heaviest shielding). With light shielding, a lethal dose of more
than 4 Gy would have been accumulated by the astronauts [
7
].
Another example in which energetic ions act as primary quanta of radiation are
˛
-emitters incorporated into the human body: For instance inhaled Radon and its
decay products emit
-particles of several MeV directly into the lung tissue where
they pose a large damage risk.
But the biological effects fast ions and ionizing radiation in general have on
living cells are not a mere result of the direct impact of high energy quanta of
radiation. The primary interaction will lead to molecular excitation, ionization and
fragmentation. In the process, the primary particle loses energy and secondary
particles such as low energy electrons, radicals but also (multiply charged) ions
are formed within the track. The interaction of these secondary particles with
biologically relevant molecules is responsible for a large fraction of biological
radiation damage to a cell [
8
].
To date, molecular mechanisms underlying the exceptional cell killing efficiency
of ions as compared to e.g. photons are largely unknown. The investigation of this
issue in macroscopic systems (
in vivo
and
in vitro
) is generally hindered by the
enormous complexity of the systems. Also, in living systems relevant timescales
range from the fs-scale of primary ionization and excitation processes over
˛
s
timescales of diffusion limited radical chemistry up to second and even year
timescales of biological processes and biological endpoints.
For a deep understanding of biological radiation damage on the level of individ-
ual molecules it is important to quantify excitation, ionization and fragmentation
cross sections as well as kinetic energies of the various primary and secondary
species. Low energy electrons (0 - 20 eV) are the most abundant secondary particles
[
9
] and the first studies on molecular mechanisms underlying biological radiation
damage have focused on low energy electron interactions with DNA. Low energy
electrons were found to cause single and double strand breaks of plasmid DNA
[
10
,
11
] but very remarkably even at almost zero kinetic energy electrons can
induce single strand breaks, with pronounced maxima between 0 and 3 eV [
12
].
