Elsevier

Seminars in Nuclear Medicine

Volume 38, Issue 5, September 2008, Pages 358-366
Seminars in Nuclear Medicine

Therapeutic Radionuclides: Biophysical and Radiobiologic Principles

https://doi.org/10.1053/j.semnuclmed.2008.05.002Get rights and content

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.

Section snippets

Energetic Particles

In general, the distribution of therapeutic radiopharmaceuticals within a targeted solid tumor is not homogeneous. This is mainly a result of (1) the inability of the radiolabeled molecules to penetrate uniformly dissimilar regions within a solid tumor mass; (2 the high interstitial pressure of solid tumors; and/or (3) differences in the binding-site densities of tumor cells. In the case of radiopharmaceuticals labeled with energetic alpha-particle and beta-particle emitters (range of emitted

Radiobiology

The deposition of energy by ionizing radiation in mammalian cells is a random process. The absorption of energy in such cells can induce certain molecular modifications that may lead to cell death. Although this process is stochastic in nature, the death of a few cells within a tissue or an organ will not have, in general, a significant effect on function. However, as the dose increases, more cells will die with the eventual impairment of tissue/organ function.8

Alpha-Particle Emitters

The application of alpha-particle-emitting radionuclides as targeted therapeutic agents continues to be of interest. When such radionuclides are selectively accumulated in the targeted tissues (eg, tumors), their decay should result in highly localized energy deposition in the tumor cells and minimal irradiation of surrounding normal host tissues.22, 23

The investigation of the therapeutic potential of alpha-particle emitters has focused mainly on astatine-211 (211At), bismuth-212 (212Bi),

Conclusions

The increase in our understanding of the dosimetry and the therapeutic potential of various modes of radioactive decay has heightened the possibility of using radiolabeled carriers in cancer therapy. Moreover, as a consequence of the great strides in genomics, the development of more precise targeting molecules is at hand. Further progress in the field of targeted radionuclide therapy is being made by the judicious design of radiolabeled molecules that match the physical and chemical

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    Supported by NIH 5 R01 CA015523.

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