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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
16
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pubmed:dateCreated |
1994-9-13
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pubmed:abstractText |
In pursuit of radiolabeled monoclonal antibodies (mAbs) with rapid urinary excretion of radioactivity from nontarget tissues, radioiodinated mAbs releasing a m-iodohippuric acid from the mAbs in nontarget tissues were designed. A novel reagent, maleimidoethyl 3-(tri-n-butylstannyl)hippurate (MIH), was synthesized by reacting N-(hydroxyethyl)maleimide with N-Boc-glycine before coupling with N-succinimidyl 3-(tri-n-butylstannyl)benzoate (ATE). MIH possessed a maleimide group for mAb conjugation and a butylstannyl moiety for high-yield and site-specific radioiodination, and the two functional groups were linked via an ester bond to release m-iodohippuric acid. To investigate the fate of radiolabels after lysosomal proteolysis, hepatic parenchymal cells were used as a model nontarget tissue and 131I-labeled MIH was conjugated with galactosyl-neoglycoalbumin (NGA). Further conjugation of [131I]MIH with a mAb against osteogenic sarcoma (OST7) after reduction of its disulfide bonds was followed up. In murine biodistribution studies, [131I]MIH-NGA exhibited rapid accumulation in the liver followed by radioactivity elimination from the liver at a rate that was identical to and faster than those of 131I-labeled NGA via direct iodination ([131I]NGA) and [131I]ATE-labeled NGA, respectively. While [131I]NGA indicated high radioactivity levels in the murine neck, stomach, and blood, such increases in the radioactivity count were not detectable by the administration of either [131I]MIH-NGA or [131I]ATE-NGA. At 6 h postinjection of [131I]MIH-NGA, 80% of the injected radioactivity was recovered in the urine. Analyses of urine samples indicated that m-iodohippuric acid was the sole radiolabeled metabolite. In biodistribution studies using [131I]-MIH-OST7 and [131I]ATE-OST7, while both 131I-labeled OST7s registered almost identical radioactivity levels in the blood up to 6 h postinjection, the former demonstrated a lower radioactivity level than [131I]ATE-OST7 in nontarget tissues throughout the experiment. Such chemical and biological characteristics of MIH would enable high target/nontarget ratios in diagnostic and therapeutic nuclear medicine using mAbs and other polypeptides.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Albumins,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Hippurates,
http://linkedlifedata.com/resource/pubmed/chemical/Indicators and Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Iodine Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Iodohippuric Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Trialkyltin Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/galactosyl-neoglycoalbumin
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
37
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pubmed:owner |
NLM
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pubmed:authorsComplete |
N
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pubmed:pagination |
2609-18
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pubmed:dateRevised |
2003-11-14
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pubmed:meshHeading |
pubmed-meshheading:8057303-Albumins,
pubmed-meshheading:8057303-Animals,
pubmed-meshheading:8057303-Antibodies, Monoclonal,
pubmed-meshheading:8057303-Chromatography, High Pressure Liquid,
pubmed-meshheading:8057303-Drug Stability,
pubmed-meshheading:8057303-Hippurates,
pubmed-meshheading:8057303-Indicators and Reagents,
pubmed-meshheading:8057303-Iodine Radioisotopes,
pubmed-meshheading:8057303-Iodohippuric Acid,
pubmed-meshheading:8057303-Isotope Labeling,
pubmed-meshheading:8057303-Kinetics,
pubmed-meshheading:8057303-Liver,
pubmed-meshheading:8057303-Lysosomes,
pubmed-meshheading:8057303-Mice,
pubmed-meshheading:8057303-Tissue Distribution,
pubmed-meshheading:8057303-Trialkyltin Compounds
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pubmed:year |
1994
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pubmed:articleTitle |
Maleimidoethyl 3-(tri-n-butylstannyl)hippurate: a useful radioiodination reagent for protein radiopharmaceuticals to enhance target selective radioactivity localization.
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pubmed:affiliation |
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
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pubmed:publicationType |
Journal Article
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