177Lu-DOTA-HH1, a Novel Anti-CD37 Radio-Immunoconjugate: A Study of Toxicity in Nude Mice
Publication Date
July 28, 2014
Journal
PLOS ONE
Authors
Ada H. V. Repetto Llamazares, Roy H. Larsen, Anna Maria Giusti, Elena Riccardi, et al
Volume
9
Issue
7
Pages
e103070
DOI
https://dx.plos.org/10.1371/journal.pone.0103070
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0103070
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/25068508
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113375
Europe PMC
http://europepmc.org/abstract/MED/25068508
Web of Science
000339993700032
Scopus
84904878044
Mendeley
http://www.mendeley.com/research/177ludotahh1-novel-anticd37-radioimmunoconjugate-study-toxicity-nude-mice
Events
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Mendeley | Further Information

{"title"=>"177Lu-DOTA-HH1, a novel anti-CD37 radio-immunoconjugate: A study of toxicity in nude mice", "type"=>"journal", "authors"=>[{"first_name"=>"Ada H.V.", "last_name"=>"Repetto-Llamazares", "scopus_author_id"=>"36089113800"}, {"first_name"=>"Roy H.", "last_name"=>"Larsen", "scopus_author_id"=>"7402880018"}, {"first_name"=>"Anna Maria", "last_name"=>"Giusti", "scopus_author_id"=>"57196879446"}, {"first_name"=>"Elena", "last_name"=>"Riccardi", "scopus_author_id"=>"57198116071"}, {"first_name"=>"Øyvind S.", "last_name"=>"Bruland", "scopus_author_id"=>"35499189900"}, {"first_name"=>"Pål Kristian", "last_name"=>"Selbo", "scopus_author_id"=>"6603234454"}, {"first_name"=>"Jostein", "last_name"=>"Dahle", "scopus_author_id"=>"7004335207"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"373631636", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0103070", "scopus"=>"2-s2.0-84904878044", "pmid"=>"25068508", "sgr"=>"84904878044"}, "id"=>"401a5703-e3bd-3fc7-80b7-ce4664a2a889", "abstract"=>"BACKGROUND 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 177Lu creating the radio-immunoconjugate (RIC) 177Lu-DOTA-HH1 (177Lu-HH1, trade name Betalutin). The present toxicity study was performed prior to initiation of clinical studies with 177Lu-HH1. METHODOLOGY/PRINCIPAL FINDINGS Nude mice with or without tumor xenografts were treated with 50 to 1000 MBq/kg 177Lu- 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 177Lu-HH1. Significant changes in serum concentrations of liver enzymes were evident for treatment with 1000 MBq/kg 177Lu-HH1. Lymphoid depletion, liver necrosis and atrophy, and interstitial cell hyperplasia of the ovaries were also observed for mice in this dose group. CONCLUSIONS/SIGNIFICANCE 177Lu-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 177Lu-HH1 in NHL patients.", "link"=>"http://www.mendeley.com/research/177ludotahh1-novel-anticd37-radioimmunoconjugate-study-toxicity-nude-mice", "reader_count"=>10, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>2, "Student > Master"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>2, "Student > Master"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Medicine and Dentistry"=>4, "Agricultural and Biological Sciences"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Belgium"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/1612072"], "description"=>"<p><b>A</b>. Normal spleen from a control mouse. <b>B</b>. Severe lymphoid depletion and reduction of extramedullary hematopoiesis in the spleen from a mouse treated with 1000 MBq/kg. <b>C</b>. Normal lymph node from a control mouse showing diffuse interstitial cell hyperplasia. This is a common background finding noted in the lymph nodes from athymic nude mice. <b>D</b>. Severe lymphoid depletion noted in the lymph node in a mouse treated with 1000 MBq/kg. <b>E</b>. Normal bone marrow from a control mouse. <b>F</b>. Severe atrophy of the bone marrow in a mouse treated with 1000 MBq/kg. <b>G</b>. Ovary from a control mouse showing the presence of growing follicles (arrows) and corporea lutea (*). <b>H</b>. Ovary from a mouse treated with 1000 MBq/kg showing follicular atrophy (arrows) and severe hyperplasia of the interstitial cells (arrowheads).</p>", "links"=>[], "tags"=>["biophysics", "Radiation biophysics", "immunology", "Clinical immunology", "Antibody therapy", "Radiobiology", "toxicology", "toxicity", "Veterinary science", "Veterinary toxicology", "oncology", "Cancer treatment", "Radiology and imaging", "Radiation effects", "Radiation exposure", "pictures", "histological", "findings", "mice", "treated", "compared"], "article_id"=>1120317, "categories"=>["Biological Sciences"], "users"=>["Ada H. V. Repetto-Llamazares", "Roy H. Larsen", "Anna Maria Giusti", "Elena Riccardi", "Øyvind S. Bruland", "Pål Kristian Selbo", "Jostein Dahle"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103070.g005", "stats"=>{"downloads"=>0, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_pictures_of_main_histological_findings_in_mice_treated_with_1000_kg_177_Lu_HH1_compared_to_control_mice_H_E_4X_/1120317", "title"=>"Representative pictures of main histological findings in mice treated with 1000/kg <sup>177</sup>Lu-HH1 compared to control mice (H/E, 4X).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-28 03:12:35"}
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  • {"files"=>["https://ndownloader.figshare.com/files/1612065"], "description"=>"<p>Error bars  =  SD, N = 4–10. <b>A</b>. Mice without xenografts treated with saline, 150 or 250 MBq/kg <sup>177</sup>Lu-HH1 (experiment 2). <b>B</b>. Mice with Ramos xenografts treated with saline or 400, 800 or 1000 MBq/kg <sup>177</sup>Lu-HH1 (experiment 3 and 4).</p>", "links"=>[], "tags"=>["biophysics", "Radiation biophysics", "immunology", "Clinical immunology", "Antibody therapy", "Radiobiology", "toxicology", "toxicity", "Veterinary science", "Veterinary toxicology", "oncology", "Cancer treatment", "Radiology and imaging", "Radiation effects", "Radiation exposure", "dosages", "bodyweight", "nude"], "article_id"=>1120310, "categories"=>["Biological Sciences"], "users"=>["Ada H. V. Repetto-Llamazares", "Roy H. Larsen", "Anna Maria Giusti", "Elena Riccardi", "Øyvind S. Bruland", "Pål Kristian Selbo", "Jostein Dahle"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103070.g003", "stats"=>{"downloads"=>1, "page_views"=>26, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_increasing_dosages_of_177_Lu_HH1_on_bodyweight_of_nude_mice_/1120310", "title"=>"Effects of increasing dosages of <sup>177</sup>Lu-HH1 on bodyweight of nude mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-28 03:12:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1612062"], "description"=>"<p><b>A</b>. Mice without xenografts treated with saline or 50, 100, 150 or 250 MBq/kg <sup>177</sup>Lu-HH1 (experiments 1 and 2). Blood samples were taken every 3 to 4 weeks, N = 4–10. Error bars  =  Standard deviation. <b>B</b>. Mice with Ramos xenografts treated with saline or 400, 800 or 1000 MBq/kg <sup>177</sup>Lu-HH1 (experiment 3 and 4). Blood samples were taken before treatment, 1 month after treatment and at euthanasia.</p>", "links"=>[], "tags"=>["biophysics", "Radiation biophysics", "immunology", "Clinical immunology", "Antibody therapy", "Radiobiology", "toxicology", "toxicity", "Veterinary science", "Veterinary toxicology", "oncology", "Cancer treatment", "Radiology and imaging", "Radiation effects", "Radiation exposure", "dosage", "cells"], "article_id"=>1120307, "categories"=>["Biological Sciences"], "users"=>["Ada H. V. Repetto-Llamazares", "Roy H. Larsen", "Anna Maria Giusti", "Elena Riccardi", "Øyvind S. Bruland", "Pål Kristian Selbo", "Jostein Dahle"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103070.g002", "stats"=>{"downloads"=>2, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_increasing_dosage_of_177_Lu_HH1_on_the_number_of_white_blood_cells_red_blood_cells_and_platelets_/1120307", "title"=>"Effects of increasing dosage of <sup>177</sup>Lu-HH1 on the number of white blood cells, red blood cells and platelets.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-28 03:12:35"}
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PMC Usage Stats | Further Information

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Relative Metric

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