title: 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.affiliation: Nordic Nanovector ASA, Kjelsåsveien 168, 0884, Oslo, Norway; Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0310, Oslo, Norway.
authors.forename: Ada H V
authors.initials: AH
authors.lastname: Repetto-Llamazares
authors.affiliation: Sciencons AS, Kjelsåsveien 168, 0884, Oslo, Norway.
authors.forename: Roy H
authors.initials: RH
authors.lastname: Larsen
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0310, Oslo, Norway.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Patzke
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0310, Oslo, Norway.
authors.forename: Karianne G
authors.initials: KG
authors.lastname: Fleten
authors.affiliation: UMR 1037 INSERM/UPS, Centre de Recherche en Cancérologie de Toulouse, Toulouse, F-31062, France.
authors.forename: David
authors.initials: D
authors.lastname: Didierlaurent
authors.affiliation: Institut de Recherche en Cancérologie de Montpellier, Institut National de la Santé et de la Recherche Médicale, U896, Université Montpellier, Montpellier, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pichard
authors.affiliation: Institut de Recherche en Cancérologie de Montpellier, Institut National de la Santé et de la Recherche Médicale, U896, Université Montpellier, Montpellier, France.
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Pouget
authors.affiliation: Nordic Nanovector ASA, Kjelsåsveien 168, 0884, Oslo, Norway.
authors.forename: Jostein
authors.initials: J
authors.lastname: Dahle
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry* / Q000276:immunology; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001610:Beta Particles; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000737:chemistry; D008187:Lutetium / Q000737:chemistry; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D011868:Radioisotopes; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000069283:Rituximab / Q000737:chemistry / Q000276:immunology; D059470:Tetraspanins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; C059071:CD37 protein, human; D018796:Immunoconjugates; D007457:Iodine Radioisotopes; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D059470:Tetraspanins; D000069283:Rituximab; D008187:Lutetium