| pubmed-article:7493333 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:7493333 | lifeskim:mentions | umls-concept:C0020792 | lld:lifeskim |
| pubmed-article:7493333 | lifeskim:mentions | umls-concept:C0003241 | lld:lifeskim |
| pubmed-article:7493333 | lifeskim:mentions | umls-concept:C0870883 | lld:lifeskim |
| pubmed-article:7493333 | lifeskim:mentions | umls-concept:C1515655 | lld:lifeskim |
| pubmed-article:7493333 | lifeskim:mentions | umls-concept:C1566673 | lld:lifeskim |
| pubmed-article:7493333 | pubmed:issue | 23 Suppl | lld:pubmed |
| pubmed-article:7493333 | pubmed:dateCreated | 1996-1-11 | lld:pubmed |
| pubmed-article:7493333 | pubmed:abstractText | The in vivo fate of various 111In-labeled polypeptides has been the subject of many investigations. Intracellular metabolism has been studied through the use of 111In-labeled glycoproteins that are concentrated in the lysosome by receptor-mediated endocytosis. These studies have indicated that the main lysosomal metabolite is 111In-chelate-epsilon-lysine, both in vitro and in vivo (Y. Arano et al., J. Nucl. Med., 35: 890-898, 1994; F. N. Franano et al., Nucl. Med. Biol., 21: 1023-1034, 1994). Since the vast majority of radiolabeled antibodies do not localize within the target tissue, an understanding of the metabolism of 111In-labeled antibodies in nontarget tissues is important for the rational design of future radiolabeled antibodies. We investigated the in vivo metabolism of 111In-DTPA3-conjugated antibody in female Sprague-Dawley rats using the anticolorectal carcinoma monoclonal antibody (MAb) 1A3 and MAb 1A3-F(ab')2. Livers and kidneys were harvested from rats injected with either intact MAb or MAb fragments and analyzed by gel filtration chromatography. Thirty-five % of the radioactivity from 111In-DTPA-1A3 MAb present in the liver was in the form of a low molecular weight species at 1 through 5 days. In contrast, 111In-DTPA-1A3-F(ab')2 was > 98% degraded to a low molecular weight species in the kidney after 1 day. In each case, the low molecular weight metabolites were collected and further analyzed by silica gel thin-layer chromatography, reversed phase high-performance liquid chromatography, and ion-exchange chromatography and compared to 111In-DTPA and 111In-DTPA-epsilon-lysine standards. In each system, the major metabolite co-eluted with 111In-DTPA-epsilon-lysine, similar to the results obtained with 111In-labeled glycoproteins that are delivered to lysosomes by receptor-mediated endocytosis. A minor metabolite that was more highly charged than 111In-DTPA was also observed. Analysis of urine and feces demonstrated that the main excretory product of both 111In-labeled intact 1A3 and 1A3-F(ab')2 was 111In-DTPA-epsilon-lysine. Based on this data, we propose that 111In-DTPA-antibodies are degraded within lysosomes of nontarget organs such as the liver and kidneys. | lld:pubmed |
| pubmed-article:7493333 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:7493333 | pubmed:language | eng | lld:pubmed |
| pubmed-article:7493333 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:7493333 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:7493333 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:7493333 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:7493333 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:7493333 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:7493333 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:7493333 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:7493333 | pubmed:issn | 0008-5472 | lld:pubmed |
| pubmed-article:7493333 | pubmed:author | pubmed-author:WelchM JMJ | lld:pubmed |
| pubmed-article:7493333 | pubmed:author | pubmed-author:DuncanJ RJR | lld:pubmed |
| pubmed-article:7493333 | pubmed:author | pubmed-author:AndersonC JCJ | lld:pubmed |
| pubmed-article:7493333 | pubmed:author | pubmed-author:ConnettJ MJM | lld:pubmed |
| pubmed-article:7493333 | pubmed:author | pubmed-author:EdwardsW BWB | lld:pubmed |
| pubmed-article:7493333 | pubmed:author | pubmed-author:FrananoF NFN | lld:pubmed |
| pubmed-article:7493333 | pubmed:author | pubmed-author:RogersB EBE | lld:pubmed |
| pubmed-article:7493333 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:7493333 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:7493333 | pubmed:volume | 55 | lld:pubmed |
| pubmed-article:7493333 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:7493333 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:7493333 | pubmed:pagination | 5714s-5720s | lld:pubmed |
| pubmed-article:7493333 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
| pubmed-article:7493333 | pubmed:meshHeading | pubmed-meshheading:7493333-... | lld:pubmed |
| pubmed-article:7493333 | pubmed:meshHeading | pubmed-meshheading:7493333-... | lld:pubmed |
| pubmed-article:7493333 | pubmed:meshHeading | pubmed-meshheading:7493333-... | lld:pubmed |
| pubmed-article:7493333 | pubmed:meshHeading | pubmed-meshheading:7493333-... | lld:pubmed |
| pubmed-article:7493333 | pubmed:meshHeading | pubmed-meshheading:7493333-... | lld:pubmed |
| pubmed-article:7493333 | pubmed:meshHeading | pubmed-meshheading:7493333-... | lld:pubmed |
| pubmed-article:7493333 | pubmed:meshHeading | pubmed-meshheading:7493333-... | lld:pubmed |
| pubmed-article:7493333 | pubmed:meshHeading | pubmed-meshheading:7493333-... | lld:pubmed |
| pubmed-article:7493333 | pubmed:meshHeading | pubmed-meshheading:7493333-... | lld:pubmed |
| pubmed-article:7493333 | pubmed:meshHeading | pubmed-meshheading:7493333-... | lld:pubmed |
| pubmed-article:7493333 | pubmed:meshHeading | pubmed-meshheading:7493333-... | lld:pubmed |
| pubmed-article:7493333 | pubmed:meshHeading | pubmed-meshheading:7493333-... | lld:pubmed |
| pubmed-article:7493333 | pubmed:year | 1995 | lld:pubmed |
| pubmed-article:7493333 | pubmed:articleTitle | Identification of metabolites of 111In-diethylenetriaminepentaacetic acid-monoclonal antibodies and antibody fragments in vivo. | lld:pubmed |
| pubmed-article:7493333 | pubmed:affiliation | Mallinckrodt Institute of Radiology, Washington University, School of Medicine, St. Louis, Missouri 63110, USA. | lld:pubmed |
| pubmed-article:7493333 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:7493333 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:7493333 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:7493333 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:7493333 | lld:pubmed |
