Linear energy transfer (LET)

Linear energy transfer (L or LET) is the average energy that a charged ionising particle transfers to the medium per unit length of its track, L = dE/dl, expressed in keV per micrometre (keV/µm). It describes the spatial density of energy deposition (and therefore of ionisation events) along a particle's path, which is what ultimately determines the biological severity of the damage caused for a given absorbed dose.

Representative values illustrate the range: cobalt-60 gamma rays and diagnostic x-rays are low-LET (roughly 0.2-2 keV/µm), beta particles from radionuclides such as lutetium-177 are also low-LET (a 1 MeV beta particle deposits roughly 0.2 keV/µm and travels several millimetres), while alpha particles are high-LET, depositing on the order of 80-150 keV/µm over a track of only tens to about a hundred micrometres (a handful of cell diameters). High-LET radiation causes densely clustered ionisations that produce more complex, harder-to-repair DNA double-strand breaks than the sparse ionisation from low-LET beta or gamma radiation, which is the physical basis for targeted alpha therapy's distinct toxicity and efficacy profile compared with beta-emitting radioligand therapy.

LET is the mechanistic quantity underlying both the regulatory radiation weighting factor used in equivalent dose (wR = 20 for alpha versus 1 for beta/gamma) and the empirically measured relative biological effectiveness used to compare therapeutic effect between alpha- and beta-emitting radiopharmaceuticals.