sup.177Lu-DOTA-HH1, a Novel Anti-CD37 Radio-Immunoconjugate: A Study of Toxicity in Nude Mice

• Published in: PloS one 2014-07, Vol.9 (7)
• Main Authors: Repetto-Llamazares, Ada H. V, Larsen, Roy H, Giusti, Anna Maria, Riccardi, Elena, Bruland, Øyvind S, Selbo, Pål Kristian, Dahle, Jostein
• Format: Article
• Language: English
• Subjects: Liver; Monoclonal antibodies; Non-Hodgkin's lymphomas
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0103070

CD37 is an internalizing B-cell antigen expressed on Non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia cells (CLL). The anti-CD37 monoclonal antibody HH1 was conjugated to the bifunctional chelator p-SCN-Bn-DOTA and labelled with the beta-particle emitting radionuclide .sup.177 Lu creating the radio-immunoconjugate (RIC) .sup.177 Lu-DOTA-HH1 (.sup.177 Lu-HH1, trade name Betalutin). The present toxicity study was performed prior to initiation of clinical studieswith .sup.177 Lu-HH1. Nude mice with or without tumor xenografts were treated with 50 to 1000 MBq/kg .sup.177 Lu- HH1 and followed for clinical signs of toxicity up to ten months. Acute, life threatening bone marrow toxicity was observed in animals receiving 800 and 1000 MBq/kg .sup.177 Lu-HH1. Significant changes in serum concentrations of liver enzymes were evident for treatment with 1000 MBq/kg .sup.177 Lu-HH1. Lymphoid depletion, liver necrosis and atrophy, and interstitial cell hyperplasia of the ovaries were also observed for mice in this dose group. .sup.177 Lu-DOTA-HH1 was well tolerated at dosages about 10 times above those considered relevant for radioimmunotherapy in patients with B-cell derived malignancies.The toxicity profile was as expected for RICs. Our experimental results have paved the way for clinical evaluation of .sup.177 Lu-HH1 in NHL patients.