Radioisotopic Localization of 90Yttrium–Ibritumomab Tiuxetan in Patients with CD20+ Non-Hodgkin’s Lymphoma

Purpose 90 Yttrium-ibritumomab-tiuxetan (Zevalin) is an effective treatment for relapsed or refractory low-grade, follicular, or transformed B-cell NHL. The purpose of this study is to assess whether tissue and cellular localization of 90 Y-ibritumomab–tiuxetan determined by autoradiography and radioactivity localized to tumor tissue might enhance our understanding of the mechanism of action of radioimmunotherapy. Methods Eight eligible patients had CD20+ NHL, a bulky peripheral lymph node, and were scheduled for 90 Y-ibritumomab–tiuxetan treatment. 2-Deoxy-2-[ F -18]fluoro- d -glucose-positron emission tomography/computed tomography (FDG-PET/CT) was performed prior to treatment and at 12 weeks after therapy for assessment of response. Bone marrow, lymph node, and blood samples were collected 114 ± 3 h after 14.8 MBq/kg 90 Y-ibritumomab-tiuxetan and processed for histology, scintillation counting, and microscopic autoradiography. Results Pericellular membrane localization of 90 Y-ibritumomab–tiuxetan to lymphoma cells was observed by autoradiography in the involved areas of lymph node with absence of significant localization in histologically normal sections of bone marrow. Pericellular radioactivity and the highest quantitative radioactivity were observed in lymph node samples of responding patients. Conclusions 90 Y-ibritumomab-tiuxetan localizes to the surface membrane of CD20+ lymphoma cells in affected lymph nodes. The patients with the highest quantitative concentration of radioactivity to the lymph node as determined by scintillation counting were observed to have a clinical and FDG-PET/CT response.