Document Detail


Human/murine chimeric 81C6 F(ab')(2) fragment: preclinical evaluation of a potential construct for the targeted radiotherapy of malignant glioma.
MedLine Citation:
PMID:  15028247     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have obtained encouraging responses in recent Phase I studies evaluating (131)I-labeled human/murine chimeric 81C6 anti-tenascin monoclonal antibody (ch81C6) administered into surgically-created tumor resection cavities in brain tumor patients. However, because the blood clearance is slow, hematologic toxicity has been higher than seen with murine 81C6 (mu81C6). In the current study, a series of paired-label experiments were performed in athymic mice bearing subcutaneous D-245 MG human glioma xenografts to compare the biodistribution of the fragment ch81C6 F(ab')(2) labeled using Iodogen to a) intact ch81C6, b) mu81C6, and c) ch81C6 F(ab')(2) labeled using N-succinimidyl 3-[(131)I]iodobenzoate. Tumor retention of radioiodine activity for the F(ab')(2) fragment was comparable to that for intact ch81C6 for the first 24 h and to that for mu81C6 for the first 48 h; as expected, blood and other normal tissue levels declined faster for ch81C6 F(ab')(2.) Radiation dosimetry calculations suggest that (131)I-labeled ch81C6 F(ab')(2) may warrant further evaluation as a targeted radiotherapeutic for the treatment of brain tumors.
Authors:
Abraham Boskovitz; Gamal H Akabani; Charles N Pegram; Darrell D Bigner; Michael R Zalutsky
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Publication Detail:
Type:  Comparative Study; Evaluation Studies; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nuclear medicine and biology     Volume:  31     ISSN:  0969-8051     ISO Abbreviation:  Nucl. Med. Biol.     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-03-18     Completed Date:  2004-12-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9304420     Medline TA:  Nucl Med Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  345-55     Citation Subset:  IM    
Affiliation:
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / pharmacokinetics*,  therapeutic use
Body Burden
Drug Evaluation, Preclinical
Feasibility Studies
Glioma / metabolism*,  radiotherapy
Humans
Immunoglobulin Fab Fragments / metabolism,  therapeutic use
Iodine Radioisotopes / pharmacokinetics*,  therapeutic use
Metabolic Clearance Rate
Mice
Mice, Nude
Organ Specificity
Radiation Dosage
Radioimmunotherapy / methods*
Radiopharmaceuticals / pharmacokinetics,  therapeutic use
Recombinant Fusion Proteins / pharmacokinetics,  therapeutic use
Tissue Distribution
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
95ER62021//PHS HHS; CA11898/CA/NCI NIH HHS; CA42324/CA/NCI NIH HHS; NS20023/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Immunoglobulin Fab Fragments; 0/Iodine Radioisotopes; 0/Radiopharmaceuticals; 0/Recombinant Fusion Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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