Therapeutic radionuclides: biophysical and radiobiologic principles

Abstract

Although the general radiobiologic principles underlying external beam therapy and radionuclide therapy are the same, there are significant differences in the biophysical and radiobiologic effects between the 2 types of radiation. In addition to the emission of particulate radiation, targeted radionuclide therapy is characterized by (1) extended exposures and, usually, declining dose rates; (2) nonuniformities in the distribution of radioactivity and, thus, absorbed dose; and (3) particles of varying ionization density and, hence, quality. This review explores the special features that distinguish the biologic effects consequent to the traversal of charged particles through mammalian cells. It also highlights what has been learned when these radionuclides and radiotargeting pharmaceuticals are used to treat cancers.

FIGURE 1

Schematic of emissions produced during decay of therapeutic radionuclides.

FIGURE 2

Ionization density along path of alpha particle as function of traversed distance.

FIGURE 3

Number of radioactive atoms required to ensure traversal of cell nucleus by one energetic particle as function of distance from center of cell. Nuclear radius to distance of decaying atom (percentage) is plotted as function of number of decays (N). R_c: cell radius; R_n: nuclear radius; D_d: distance of decaying atom from center of cell for one nuclear traversal. Note that (i) nuclear localization of radioactive atom is the only condition that will lead to one traversal per decaying atom; (ii) when decaying atoms are on nuclear membrane, ≥2 radioactive atoms are needed for one nuclear traversal; and (iii) when decaying atoms are localized on cell membrane and diameter of cell is twice that of nucleus, >15 radioactive atoms are necessary to ensure one nuclear traversal.

FIGURE 4

Linear energy transfer (LET) along paths of energetic beta particles and Auger electrons as function of traversed distance.

FIGURE 5

Schematic representation of ionization densities produced along tracks of energetic beta particles, Auger electrons, and alpha particles.

FIGURE 6

Mammalian cell survival curves after high- and low-LET irradiation. With high-LET radiation (alpha and nonenergetic electrons), curve shows exponential decrease in survival; with low-LET radiation (energetic electrons), curve exhibits a shoulder.

FIGURE 7

Schematic representation of relationship between mammalian cell survival and alpha- and beta-particle-emitter distribution as function of dose. Solid lines: uniform irradiation; broken lines: nonuniform irradiation.