Principles of radioimmunotherapy for hematologists and oncologists

Recent trials with radiolabeled monoclonal antibodies targeting lymphoid surface membrane antigens have shown high response rates and tolerable toxicity. Radiolabeled antibodies emit continuous, exponentially decreasing, low-dose-rate radiation, whereas conventional external-beam radiotherapy delivers intermittent, fractionated radiation at higher dose rates. The most common isotopes used for radioimmunotherapy (iodine 131 and yttrium 90) kill cells primarily by emission of beta particles (electrons), which are believed to induce DNA strand breaks. The beta particles of Y 90 are more energetic than those of I 131, and affect cells over a radius of 5 mm compared with 0.9 mm to 1.0 mm for I 131. In addition, I 131 emits long-range gamma rays that permit direct imaging with a gamma camera, but also deliver a whole-body radiation dose and may pose a risk to health care workers. Physical barriers to effective delivery of radioimmunotherapy include the heterogeneous tumor vasculature, slow diffusion and convection rates of large antibody molecules through the interstitial fluid, heterogeneous biodistribution of antibodies in tumor nodules, and high intratumoral pressures impeding antibody influx into tumors. Despite these obstacles, multiple trials have shown the efficacy of radioimmunotherapy, particularly for B-cell lymphomas treated with anti-CD20 antibodies, in which response rates of 60% to 90% have been reported.