The Department of Radiation Oncology at Cleveland Clinic is at the cutting edge of research in pioneering the use of several specialized lymphoma radiotherapy treatment techniques. For certain types of indolent lymphomas, the use of radio-labeled antibodies as a form of experimental "systemic radiotherapy" is under evaluation. Several different antibodies bound to several different isotopes have been used in clinical trials at Cleveland Clinic.

The advantage of this approach, as opposed to the brachytherapy programs, is that the "targeted radiotherapy" can be injected into the circulation and allowed to localize simultaneously in many different sites of disease involvement. Although the exact level of clinical effectiveness for this sort of radiotherapy treatment will vary depending on the case, 60-80% or more of patients who receive this sort of radiotherapy treatment will demonstrate a good clinical response even for fairly advanced cases, with a 20-40% complete response rate.

In the US there are currently 2 FDA-cleared radiolabeled antibodies that are in use at Cleveland Clinic and elsewhere: Y-90 ibritumomab tiuxetan ("Zevalin") and I-131-tositumomab (“Bexxar”). Both are approved for the treatment of relapsed refractory and transformed indolent B cell NHL. Both have also shown dramatic effects in frontline treatment for indolent lymphoma and are currently seeking approval for this "radio-immunotherapy" indication in the US. This approval was granted in Europe in 2008.