## Metrics

### Ionization Density: Linear Energy Transfer

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.

X ray Alpha Particle
Gamma ray Neutron
Proton

### Relative Biological Effectiveness

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:

${\displaystyle RBE={\frac {Dose_{s}}{Dose_{t}}}}$

where ${\displaystyle Dose_{s}}$  is the dose from standard radiation to produce an effect and ${\displaystyle Dose_{t}}$  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

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:

${\displaystyle OER={\frac {Dose_{h}}{Dose_{n}}}}$

where ${\displaystyle Dose_{h}}$  is the dose to produce an effect in hypoxic conditions and ${\displaystyle Dose_{n}}$  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.

## Cell Survival Curves

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.

SF = e-αD-βD2