Radiation therapy uses ionizing radiation to kill cancer cells and shrink tumors by damaging the cells’ DNA, thereby stopping these cells from continuing to grow and divide. The most common way of exposing cancer patients to radiation is through external radiation therapy. With this approach, only a limited area of the body is irradiated by delivering a beam of high-energy x rays to the main tumor. Targeted radionuclide therapy, on the other hand, is like chemotherapy, because it is a systemic treatment; it uses a molecule labeled with a radionuclide to deliver a toxic level of radiation to disease sites. Unlike tumor-directed drugs and toxins, which kill only the directly targeted cells, a unique feature of radionuclides is that they can exert a “bystander” or “crossfire” effect (Figure 4.1), potentially destroying adjacent tumor cells even if they lack the specific tumor-associated antigen or receptor. In addition, a systemically administered targeted radiotherapeutic that combines the specificity of cancer cell targeting with the known antitumor effects of ionizing radiation has the potential to simultaneously eliminate both a primary tumor site and cancer that has spread throughout the body, including malignant cell populations undetectable by diagnostic imaging. Figure 4.2 illustrates and contrasts the differences between direct and bystander killing of tumors.
In targeted radionuclide therapy, the biological effect is obtained by energy absorbed from the radiation emitted by the radionuclide. Whereas the radionuclides used for nuclear medicine imaging emit gamma rays, which can penetrate deeply into the body, the radionuclides used for targeted radionuclide therapy must emit radiation with a relatively short path length. There are three types of particulate radiation of consequence for targeted radionuclide therapy—beta particles, alpha particles,1 and Auger
An alpha particle is sub-atomic matter consisting of two protons and two neutrons.