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

(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.