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

Abstract	177Lu-DOTA-HH1 (177Lu-HH1) is a novel anti-CD37 radioimmunoconjugate developed to treat non-Hodgkin lymphoma. Mice with subcutaneous Ramos xenografts were treated with different activities of 177Lu-HH1, 177Lu-DOTA-rituximab (177Lu-rituximab) and non-specific 177Lu-DOTA-IgG1 (177Lu-IgG1) 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 177Lu-HH1 as compared with mice treated with similar activities of 177Lu-rituximab or non-specific 177Lu-IgG1, 0.9% NaCl or unlabeled HH1. All mice injected with 530 MBq/kg of 177Lu-HH1 tolerated the treatment well. In contrast, 6 out of 10 mice treated with 530 MBq/kg 177Lu-rituximab experienced severe radiation toxicity. The retention of 177Lu-rituximab in organs of the mononuclear phagocyte system was longer than for 177Lu-HH1, which explains the higher toxicity observed in mice treated with 177Lu-rituximab. In vitro internalization studies showed that 177Lu-HH1 internalizes faster and to a higher extent than 177Lu-rituximab which might be the reason for the better therapeutic effect of 177Lu-HH1.
Authors	Ada H V Repetto-Llamazares, Roy H Larsen, Sebastian Patzke, Karianne G Fleten, David Didierlaurent, Alexandre Pichard, Jean Pierre Pouget, Jostein Dahle
Journal	PloS one (PLoS One) Vol. 10 Issue 6 Pg. e0128816 ( 2015) ISSN: 1932-6203 [Electronic] United States
PMID	26066655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antibodies Antigens, Neoplasm CD37 protein, human Immunoconjugates Iodine Radioisotopes Radioisotopes Radiopharmaceuticals Tetraspanins Rituximab Lutetium
Topics	Animals Antibodies (chemistry, immunology) Antigen-Antibody Reactions Antigens, Neoplasm (chemistry, immunology, metabolism) Beta Particles Cell Line, Tumor Disease Models, Animal Humans Immunoconjugates (chemistry, pharmacokinetics, therapeutic use) Iodine Radioisotopes (chemistry) Lutetium (chemistry) Lymphoma, Non-Hodgkin (drug therapy, mortality, pathology) Mice Mice, Nude Radioisotopes Radiopharmaceuticals (chemistry, pharmacokinetics, therapeutic use) Rituximab (chemistry, immunology) Tetraspanins (chemistry, immunology, metabolism) Tissue Distribution Transplantation, Heterologous

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