MIRD Pamphlet No. 22 (abridged): radiobiology and dosimetry of alpha-particle emitters for targeted radionuclide therapy

Abstract

The potential of alpha-particle emitters to treat cancer has been recognized since the early 1900s. Advances in the targeted delivery of radionuclides and radionuclide conjugation chemistry, and the increased availability of alpha-emitters appropriate for clinical use, have recently led to patient trials of radiopharmaceuticals labeled with alpha-particle emitters. Although alpha-emitters have been studied for many decades, their current use in humans for targeted therapy is an important milestone. The objective of this work is to review those aspects of the field that are pertinent to targeted alpha-particle emitter therapy and to provide guidance and recommendations for human alpha-particle emitter dosimetry.

FIGURE 1

Illustration of difference in ionization density between low- and high-LET tracks. (Reprinted with permission of (153).)

FIGURE 2

LET vs. distance traveled in tissue for α-particles with 2 different initial kinetic energies. α-Particles emitted with lower initial energy are closer to their Bragg peak and, therefore, start out with higher LET. LET of electrons with initial energy of 100–500 keV is also shown at bottom of plot for comparison. (Plot generated using data from (108).)

FIGURE 3

Single high-LET track has high probability of yielding DNA DSB, whereas probability of DSB induction with low-LET tracks becomes comparable only at higher absorbed doses. (Reprinted with permission of (154).)

FIGURE 4

Dependence of mean free path on LET. LET is plotted (e.g., from 200 to 100 keV/µm after 250 keV/µm) so that stopping powers on low-energy side of Bragg peak can be identified. (Reprinted with permission of (51).)

FIGURE 5

Survival curves obtained with ²¹⁰Po α-particles (–4) or 250-kVp x-rays (–8) and with different cell lines: R₁ cells derived from rhabdomyosarcoma of rat (1 and 8), subline of human kidney cell line T₁ with mean chromosome number of 121 (2 and 5), subline of T₁ with 62 chromosomes (3 and 6), and subline of T₁ with 63 chromosomes (4 and 7). (Adapted from (155).)

FIGURE 6

OER as function of LET. OER was measured using cultured human kidney-derived cells incubated in air or nitrogen. α-Particles of different energies generated by cyclotron or 250-kVp x-rays (average LET ≈ 1.3 keV/µm) were used. (Data replotted from (24).)

FIGURE 7

Effect of fractionation on cell survival: cell survival curve obtained with single doses of 200-kV x-rays (a), curve obtained when 200-kV x-ray doses are separated by 12 h (4.5 Gy, then 2.5 or 4.5 Gy) (b), and curve obtained with 3.4-MeV α-particles (c). In (c), circles correspond to single exposure, and squares to 2 equal exposures separated by 12 h. (Adapted from (26).)

FIGURE 8

Decay scheme for ²¹³Bi.