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PLoS One. 2015 Jun 11;10(6):e0128816. doi: 10.1371/journal.pone.0128816. eCollection 2015.

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

Author information

1
Nordic Nanovector ASA, Kjelsåsveien 168, 0884, Oslo, Norway; Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0310, Oslo, Norway.
2
Sciencons AS, Kjelsåsveien 168, 0884, Oslo, Norway.
3
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0310, Oslo, Norway.
4
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0310, Oslo, Norway.
5
UMR 1037 INSERM/UPS, Centre de Recherche en Cancérologie de Toulouse, Toulouse, F-31062, France.
6
Institut de Recherche en Cancérologie de Montpellier, Institut National de la Santé et de la Recherche Médicale, U896, Université Montpellier, Montpellier, France.
7
Nordic Nanovector ASA, Kjelsåsveien 168, 0884, Oslo, Norway.

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.

PMID:
26066655
PMCID:
PMC4466226
DOI:
10.1371/journal.pone.0128816
[Indexed for MEDLINE]
Free PMC Article

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