NEOPLASIA Comparison of anti-CD20 and anti-CD45 antibodies for conventional and pretargeted radioimmunotherapy of B-cell lymphomas

Radiolabeled anti-CD20 antibodies pro-duce responses in 60 % to 95 % of patients with relapsed non-Hodgkin lymphoma (NHL); however, absorbed radiation ra-tios between tumors and normal organs are relatively low, and many patients have relapses. In this study we compared the abilities of anti-CD45 (BC8) and anti-CD20 (1F5) antibodies to target human Ramos lymphoma xenografts in athymic mice. When direct radioiodination was per-formed with conventional methods, BC8 delivered 2- to 4-fold more radioiodine to tumors than 1F5, with tumor-to–normal organ ratios as high as 20:1 using radiola-beled BC8 compared with a maximal ratio of 9.8:1 using radioiodinated 1F5. To opti-mize the biodistribution of radioactivity, we performed studies following a pretar-geting method using streptavidin (SA)– conjugated BC8 and 1F5. Injection of a synthetic clearing agent decreased the circulating level of conjugates by 80 % to 90 % within 1 hour. Pretargeting with BC8-SA resulted in a 2- to 4-fold greater tumor up-take of radiolabeled biotin than with 1F5-SA, with maximal tumor-to–normal organ ratios of more than 80:1 and approxi-mately 16:1, respectively. Therapy experi-ments demonstrated that 400 Ci (14.8 MBq) or more of yttrium-90-1,4,7,10-tet-raazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)–biotin cured 100 % of mice treated with BC8-SA and more than 90% of mice pretargeted with 1F5-SA, with complete remission occurring 8 to 10 days sooner in mice receiving BC8-SA. After treatment with 200 Ci (7.4 MBq) 90Y-DOTA-biotin, 70 % of the mice treated with BC8-SA were cured, but no mice were cured using 1F5-SA. Doses up to 800 Ci (29.6 MBq) 90Y-DOTA-biotin were delivered with minor toxicity using either antibody conjugate. These lymphoma xenograft data suggest that pretargeted radioimmunotherapy using either anti-CD20 or anti-CD45 conjugates is highly effective and minimally toxic. (Blood