5-(125I)-iododeoxyuridine and the Auger effect: biological consequences and implications for therapy.

Abstract

If the full potential for the use of radionuclides in the treatment of cancer is to be realized, the problem of locating internal emitters with a short range of action in the sensitive targets of the cell must be solved. It is already clear that only two types of radioactivity will satisfy these requirements: alpha decay and, as this review has attempted to demonstrate, electron capture with subsequent Auger cascade. Although mechanisms have yet to be clarified, it is clear that an Auger emitter located within the genetic apparatus is extremely radiotoxic with as little as a single disintegration being lethal in some organisms. Moreover, the available experimental evidence suggests that the extreme lethality is confined to a very small volume, probably that of molecular dimensions. These facts highlight the advantages as well as the limitations of using the Auger effect for cancer therapy. A favorable feature is that extreme damage is confined only to the cell in which radioactive decay takes place; a disadvantage is that the biochemical specificities are very great. Not only must the radioactivity be directed specifically to malignant calls, but it must also be very closely approximated to their genetic structures as well. This circumstance has its counterpart in considering the use of electron capture emitters for diagnostic purposes since their potential hazard depends in large measure on their cellular localization. These microscopic considerations have largely been neglected in traditional radionuclide dosimetry but, considering the magnitude of the effect and the widespread use of such radionuclides as chromium-51, gallium-67, selenium-75, iodine-123, and thallium-201, they should be reexamined. In some cases, such as with 67Ga, we may find that standard dosimetric calculations have overestimated the hazard. In others, the opposite may be true. Whichever the result, it should serve as an impetus to obtain data on the cellular localization of commonly employed radionuclides and on the microscopic distribution of dose. Lastly, it is clear that Auger emitters can be used as ultramicroscopic probes to define the radiosensitive targets of the cell and to destroy regions of subcellular dimensions. This potential use in radiation and cellular biology has only now begun to be exploited.