sup.177Lu-DOTA-HH1, a Novel Anti-CD37 Radio-Immunoconjugate: A Study of Toxicity in Nude Mice
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...
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| creator | Repetto-Llamazares, Ada H. V Larsen, Roy H Giusti, Anna Maria Riccardi, Elena Bruland, Øyvind S Selbo, Pål Kristian Dahle, Jostein |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0103070 |
| format | Article |
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V ; Larsen, Roy H ; Giusti, Anna Maria ; Riccardi, Elena ; Bruland, Øyvind S ; Selbo, Pål Kristian ; Dahle, Jostein</creator><creatorcontrib>Repetto-Llamazares, Ada H. V ; Larsen, Roy H ; Giusti, Anna Maria ; Riccardi, Elena ; Bruland, Øyvind S ; Selbo, Pål Kristian ; Dahle, Jostein</creatorcontrib><description>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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0103070</identifier><language>eng</language><publisher>Public Library of Science</publisher><subject>Liver ; Monoclonal antibodies ; Non-Hodgkin's lymphomas</subject><ispartof>PloS one, 2014-07, Vol.9 (7)</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,27901,27902</link.rule.ids></links><search><creatorcontrib>Repetto-Llamazares, Ada H. 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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.</description><subject>Liver</subject><subject>Monoclonal antibodies</subject><subject>Non-Hodgkin's lymphomas</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNqNz1FLwzAQB_AiCs7pN_AhIAiCqUnTJY1vZVM3mBts0zcZWXutGW0zlkS2b29BHzbwQe7hfxy_O7gguKYkpEzQh7Xx20ZV4cY0EBJKGBHkJOhQySLMI8JOD_rz4MLaNSE9lnDeCT6s34RUiLHHg-kixcMhvUcKTcwXVChtnMb9ARNopnJt8KiufWMy06x9qRw8ohTNnc_3yBRoYXY6026PdIMmPgf0qjO4DM4KVVm4-s1u8Pb8tOgP8Xj6MuqnY1xSzjmWPGEiznkSFxEXqzaILArSiyjAKpZSgGIxA5CQyIgqFSWxIAnwWK16gsicdYObn7ulqmCpm8K4rcpqbbNlGlPBRUQi3qrwD9VWDrVuv4JCt_OjhbujhdY42LlSeWuXo_ns_3b6fmxvD-wnqMp9WlN5p01jD-E3vPiL6w</recordid><startdate>20140728</startdate><enddate>20140728</enddate><creator>Repetto-Llamazares, Ada H. 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V ; Larsen, Roy H ; Giusti, Anna Maria ; Riccardi, Elena ; Bruland, Øyvind S ; Selbo, Pål Kristian ; Dahle, Jostein</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g1666-968374d684f267b84f09ff0521eeb4997ea343ee9e8921aa284708e64ab5709d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Liver</topic><topic>Monoclonal antibodies</topic><topic>Non-Hodgkin's lymphomas</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Repetto-Llamazares, Ada H. V</creatorcontrib><creatorcontrib>Larsen, Roy H</creatorcontrib><creatorcontrib>Giusti, Anna Maria</creatorcontrib><creatorcontrib>Riccardi, Elena</creatorcontrib><creatorcontrib>Bruland, Øyvind S</creatorcontrib><creatorcontrib>Selbo, Pål Kristian</creatorcontrib><creatorcontrib>Dahle, Jostein</creatorcontrib><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Repetto-Llamazares, Ada H. V</au><au>Larsen, Roy H</au><au>Giusti, Anna Maria</au><au>Riccardi, Elena</au><au>Bruland, Øyvind S</au><au>Selbo, Pål Kristian</au><au>Dahle, Jostein</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>sup.177Lu-DOTA-HH1, a Novel Anti-CD37 Radio-Immunoconjugate: A Study of Toxicity in Nude Mice</atitle><jtitle>PloS one</jtitle><date>2014-07-28</date><risdate>2014</risdate><volume>9</volume><issue>7</issue><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><pub>Public Library of Science</pub><doi>10.1371/journal.pone.0103070</doi></addata></record> |
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| subjects | Liver Monoclonal antibodies Non-Hodgkin's lymphomas |
| title | sup.177Lu-DOTA-HH1, a Novel Anti-CD37 Radio-Immunoconjugate: A Study of Toxicity in Nude Mice |
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