Biodistribution of 131I-, 186Re-, 177Lu-, and 88Y-Labeled hLL2 (Epratuzumab) in Nude Mice with CD22-Positive Lymphoma

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Abstract
Radioimmunotherapy (RIT) is a new and effective treatment modality in patients with non-Hodgkin's lymphoma. The monoclonal antibody (mAb) hLL2 (epratuzumab), a humanized mAb directed against the CD22 antigen, and which internalizes, can be labeled with various radionuclides. The biodistribution of hLL2 labeled with 131I, 186Re, 177Lu, and 88Y was studied in nude mice with subcutaneous human lymphoma xenografts in order to determine the most suitable of these four radionuclides for RIT with hLL2. Methods: Human Ramos lymphoma xenografts were transplanted in cyclophosphamide-pretreated athymic BALB/c mice. Four groups of mice were injected intravenously with 131I-, 186Re-, 88Y-, or 177Lu-labeled hLL2, respectively. To determine the nonspecific tumor uptake, two groups of mice received 88Y-labeled or 131I-labeled control antibody, cG250. The biodistribution of the radiolabel was determined 1, 3, and 7 days postinjection (p.i.). Results: Radiolabeled hLL2 had a higher tumor uptake than the nonspecific mAb at all time-points, irrespective of the radiolabel used. Tumor accretion of 88Y- and 177Lu-hLL2 was higher than tumor uptake of 131I- and 186Re-hLL2. Activity in the bone, represented by the femur without bone marrow, was higher for 177Lu- and 88Y-hLL2 than for 131I- and 186Re-hLL2 on day 7 p.i. Conclusion: The use of the residualizing radiolabels 88Y and 177Lu in combination with a mAb directed against an internalizing antigen resulted in higher uptake and better retention of the radiolabel in the tumor.

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