Radiation Biology for Physical Scientists/Mathematics of Radiation Biology

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Cell Response to Radiation Mutagenesis · Imaging Tumour Physiology

Metrics[edit]

Ionization Density: Linear Energy Transfer[edit]

Ionization from radiation in biological material leads to a random and uneven distribution of deposited energy in cells. The spatial distribution of the energy imparted by the charged particle is quantified by the Linear Energy Transfer (LET) metric. It is the quotient of the average energy imparted and the distance traversed by the radiation with units of keV/μm.

Radiation can be reclassified into low LET or high LET radiation based on their LET value. The demarcation value between low and high LET is about 10 keV/μm.

Low LET Radiation High LET Radiation
X ray Alpha Particle
Gamma ray Neutron
Proton

Relative Biological Effectiveness[edit]

As the LET of radiation increases, the ability of the radiation to produce biological damage also increases. The relative biological effectiveness (RBE) compares the dose of test radiation to the dose of standard radiation to produce the same biological effect. The standard radiation has been taken as 250 kVp X rays for historical reasons, but is now recommended to be Cobalt 60 gamma rays.

Mathematically, the RBE is defined by the following ratio:

where is the dose from standard radiation to produce an effect and is the dose from test radiation to produce the same effect.

The RBE peaks when the separation between ionizing events coincides with the diameter of the DNA double helix (~ 2 nanometers).

Oxygen Enhancement Ratio[edit]

In the presence of molecular oxygen (as little as a few hundred ppm) damage to DNA caused by free radicals can become "fixed" (i.e. permanent). This oxygen effect is considered since two-thirds of DNA damage is caused by free radicals.Tumor cells that are oxygen depleted (i.e. hypoxic) are thus more highly resistant to ionizing radiation.

The oxygen enhancement ratio determined by calculating the ratio of doses in hypoxic and normaxic conditions for a given isoeffect. Mathematically, it is expressed as:

where is the dose to produce an effect in hypoxic conditions and is the dose to produce the same effect in normoxic conditions.

The oxygen enhancement ratio (OER) is typically lower for high LET radiation than for low LET radiation. The OER for electrons produced by x-rays may be as high as 3 while that for alpha particles is close to unity.

Biologically Effective Dose[edit]

Cell Survival Curves[edit]

The biological effects of radiation have historically been measured with cell survival curves. These curves model the relationship between a given dose of radiation and the fraction of cells surviving in cell cultures. Examples of cell-survival curves are shown on the left.

Black: Cell surviving curve for single fraction treatments of high LET and low LET radiation Red:Cell surviving curve for multi-fractionated treatment. Courtesy of Régis Lachaume

Several mathematical methods have been developed to define the shape with the Linear Quadratic Model being most used.

Linear Quadratic Model[edit]

This model assumes there are two main ways to generate double strand breaks and subsequently cell death. The first way is caused by a single particle breaking both strands and is proportional to dose. This is the linear component of cell killing. The second way involves two independent breaks in opposite strand and is proportional to dose squared. This is the quadratic component of cell killing.

The combined effect of the linear and quadratic components of cell kill on the cell surviving fraction is given by

SF = e-αD-βD2

where alpha is a constant describing the linear component while the small constant beta describes the quadratic component. Alpha has units of Gray-1 while beta has units of Gray-2.

The ratio of alpha/beta gives the dose at which the linear and quadratic components of cell killing are equal. The typical values for tumours are ~3Gray and ~10Gray for normal tissues.