| Biodistribution and clearance of small molecule hapten chelates for pretargeted radioimmunotherapy. | |
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MedLine Citation:
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PMID: 20533093 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: The favorable pharmacokinetics and clinical safety profile of metal-chelated 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) suggests that it might be an ideal hapten for pretargeted radioimmunotherapy. In an effort to minimize hapten retention in normal tissues and determine the effect of various chemical adducts on in vivo properties, a series of DOTA-based derivatives were evaluated. PROCEDURES: Biodistribution and whole-body clearance were evaluated for (177)Lu-labeled DOTA, DOTA-biotin, a di-DOTA peptide, and DOTA-aminobenzene in normal CD1 mice. Kidney, liver, and bone marrow doses were estimated using standard Medical Internal Radiation Dose methodology. RESULTS: All haptens demonstrated similar low tissue and whole-body retention, with 2-4% of the injected dose remaining in mice 4 h postinjection. The kidney is predicted to be dose limiting for all (177)Lu-labeled haptens tested with an estimated kidney dose of approximately 0.1 mGy/MBq. CONCLUSIONS: We present here a group of DOTA-based haptens that exhibit rapid clearance and exceptionally low whole-body retention 4 h postinjection. Aminobenzene, tyrosine-lysine, and biotin groups have minimal effects on the blood clearance and biodistribution of (177)Lu-DOTA. |
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Authors:
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Kelly Davis Orcutt; Khaled A Nasr; David G Whitehead; John V Frangioni; K Dane Wittrup |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Volume: 13 ISSN: 1860-2002 ISO Abbreviation: Mol Imaging Biol Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-09 Completed Date: 2011-06-20 Revised Date: 2012-01-31 |
Medline Journal Info:
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Nlm Unique ID: 101125610 Medline TA: Mol Imaging Biol Country: United States |
Other Details:
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Languages: eng Pagination: 215-21 Citation Subset: IM |
Affiliation:
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Department of Chemical Engineering, Massachusetts Institute of Technology, 400 Main Street E19-551, Cambridge, MA 02139, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chelating Agents / administration & dosage, chemistry, pharmacokinetics*, pharmacology Dose-Response Relationship, Radiation Haptens / administration & dosage, chemistry, metabolism*, pharmacology Injections, Intravenous Male Mice Organ Specificity* / drug effects Organometallic Compounds / administration & dosage, chemistry, pharmacokinetics*, pharmacology Radioimmunotherapy / methods* Tissue Distribution / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA101830-07/CA/NCI NIH HHS; R01-CA-101830/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chelating Agents; 0/Haptens; 0/Organometallic Compounds |
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