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- and¹⁸⁶Re-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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Biodistribution of 131 I-,186 Re-,177 Lu-,and 88 Y-Labeled hLL2 (Epratuzumab) in Nude Mice with CD22-Positive Lymphoma