Biodistribution of 131I-, 186Re-, 177Lu-, and 88Y-labeled hLL2 (Epratuzumab) in nude mice with CD22-positive lymphoma.
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 (131)I, (186)Re, (177)Lu, and (88)Y 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 (131)I-, (186)Re-, (88)Y-, or (177)Lu-labeled hLL2, respectively. To determine the nonspecific tumor uptake, two groups of mice received (88)Y-labeled or (131)I-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 (88)Y- and (177)Lu-hLL2 was higher than tumor uptake of (131)I- and (186)Re-hLL2. Activity in the bone, represented by the femur without bone marrow, was higher for (177)Lu- and (88)Y-hLL2 than for (131)I- and (186)Re-hLL2 on day 7 p.i.


CONCLUSIONS
The use of the residualizing radiolabels (88)Y and (177)Lu in combination with a mAb directed against an internalizing antigen resulted in higher uptake and better retention of the radiolabel in the tumor.
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D015815:Cell Adhesion Molecules; D004386:Duodenum / Q000378:metabolism; D005260:Female; D005269:Femur / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism; D037102:Lectins / Q000276:immunology*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008187:Lutetium / Q000097:blood / Q000493:pharmacokinetics; D008223:Lymphoma / Q000737:chemistry / Q000378:metabolism / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009132:Muscles / Q000378:metabolism; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012211:Rhenium / Q000097:blood / Q000493:pharmacokinetics; D051918:Sialic Acid Binding Ig-like Lectin 2; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D015021:Yttrium Radioisotopes / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D007457:Iodine Radioisotopes; D037102:Lectins; D011868:Radioisotopes; D051918:Sialic Acid Binding Ig-like Lectin 2; D015021:Yttrium Radioisotopes; C448700:epratuzumab; D008187:Lutetium; D012211:Rhenium