Answer to Question #11416 Submitted to "Ask the Experts"

Could you explain the relationship between linear energy transfer (LET) and the relative biological effectiveness (RBE) of radiation?

The concepts of LET and RBE are distinct; they are related but not always in a quantitatively predictable fashion.

The LET is a physical quantity, representing the amount of energy transferred to electrons per unit path length traversed by charged particles set free by radioactive decay and/or by radiation interactions in a given material. Common dimensions for LET are kiloelectronvolt per micrometer (keV µm^-1), and the material of interest is often soft tissue when we are concerned with the potential biological impact of the radiation.

The quantity RBE is quite different in that it represents the ratio of the absorbed dose of a reference radiation in a target volume to the absorbed dose of radiation of interest in the same target, each dose yielding the same degree of biological impact of a specific type. Effects of concern may be (1) of a deterministic nature (nonstochastic effects), such as cataract induction, in which a threshold dose must be reached before the effect is observed; or (2) of a stochastic nature, such as some types of cancer induction, in which it is assumed that the probability of observing the effect varies with the dose with no apparent threshold.

It has been shown that for many biological endpoint effects, the extent of the biological effect increases with increasing LET of the radiation. The reference radiation that is typically used when evaluating RBE is low-LET x-ray or gamma-ray radiation for which the RBE is 1.0. When certain biological effects of high-LET radiation (such as fast neutrons) on human cells are evaluated, the RBE may vary widely, ranging from about 3 to greater than 100 for a variety of effects. Higher RBEs for neutron radiation are associated with high-LET effects from protons set free by neutron collisions with hydrogen nuclei and transferring energy to electrons through collision interactions.

The LET has limited use in predicting the extent of biological impact because, while it does provide an accurate indication of the expected energy loss by a particle and transfer to tissue electrons, it does not provide an accurate indication of the actual energy deposited in small target volumes of interest, such as individual cells. This is partly because the electrons that received energy may deposit an indeterminate amount of their energy in the target volume. You might recall that the LET quantity has been used by health physicists in the past to determine the value of the radiation quality factor (now referred to as the radiation weighting factor), which has been used as a multiplier to convert absorbed dose to equivalent dose. This is acceptable for implementing radiation protection criteria for routine applications for radiation workers, but it is not sufficient for making quantitative correlations with RBE for many different biological endpoints.

Although there may be a relationship between RBE and LET, experimental work must be conducted to determine what the value of the RBE is for a given endpoint. While the RBE often increases with LET, the relationship is not always obvious. It is typical for RBE values to reach a maximum as saturation effects of energy deposition become evident. In some cases the RBE may increase with increasing LET and then decline above certain LET values. A paper by Takatsuji et al. discusses the relationship between LET and RBE for certain chromosomal aberrations and cell death: it states that at low doses the RBE varies as about the square of the LET, the RBE value peaks at an LET of about 100 keV µm^-1, and then the RBE decreases as LET increases further.

There is no question that LET is a parameter whose magnitude yields some information about the possible significance of the RBE, but quantitative predictions of RBE values from LET values are generally not possible. Such variations as changes in RBE values with dose magnitude; dependence of the RBE on the specific endpoint effect of concern; changes in LET, especially at lower energies as charged particles traverse cells and lose energy; and other factors make it difficult to express reliable LET-RBE correlations.

George Chabot, PhD

Reference
Takatsuji T, Yoshikawa I, Sasaki MS. Generalized concept of the LET-RBE relationship of radiation-induced chromosome aberration and cell death. J Radiat Res 40(1):59–69; 1999.