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177 Lu-DOTA-HH1 ( 177 Lu-HH1) is a novel anti-CD37 radioimmunoconjugate developed to treat non-Hodgkin lymphoma. Mice with subcutaneous Ramos xenografts were treated with different activities of  177 Lu-HH1,  177 Lu-DOTA-rituximab ( 177 Lu-rituximab) and non-specific  177 Lu-DOTA-IgG 1  ( 177 Lu-IgG 1 ) and therapeutic effect and toxicity of the treatment were monitored. Significant tumor growth delay and increased survival of mice were observed in mice treated with 530 MBq/kg  177 Lu-HH1 as compared with mice treated with similar activities of  177 Lu-rituximab or non-specific  177 Lu-IgG1, 0.9% NaCl or unlabeled HH1. All mice injected with 530 MBq/kg of  177 Lu-HH1 tolerated the treatment well. In contrast, 6 out of 10 mice treated with 530 MBq/kg  177 Lu-rituximab experienced severe radiation toxicity. The retention of  177 Lu-rituximab in organs of the mononuclear phagocyte system was longer than for  177 Lu-HH1, which explains the higher toxicity observed in mice treated with  177 Lu-rituximab.  In vitro  internalization studies showed that  177 Lu-HH1 internalizes faster and to a higher extent than  177 Lu-rituximab which might be the reason for the better therapeutic effect of  177 Lu-HH1.

Targeted Cancer Therapy with a Novel Anti-CD37 Beta-Particle Emitting Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma