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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2010-3-31
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pubmed:abstractText |
Uniform antibody microdistribution throughout tumor nodules is crucial for antibody-targeted therapy, because non-uniform microdistribution leads to suboptimal therapeutic effect, a commonly observed limitation of therapeutic antibodies. Herein, we evaluated the microdistribution of different doses of intraperitoneally injected fluorescence-labeled full-antibody trastuzumab (15, 50, and 150 microg) and its Fab fragment (trastuzumab-Fab: 15 and 50 microg) in a mouse model of ovarian cancer with peritoneal disseminated tumor. A semiquantitative approach (central/peripheral accumulation ratio; C/P ratio) was developed using in situ fluorescence microscopy. Furthermore, we compared the microdistribution of intact trastuzumab with a mixed injection of trastuzumab and trastuzumab-Fab or serial injections of trastuzumab using in situ multicolor fluorescence microscopy. Fluorescence images after the administration of 15 or 50 microg trastuzumab and 15 microg trastuzumab-Fab demonstrated antibody accumulation in the tumor periphery, whereas administration of 150 microg trastuzumab and 50 microg trastuzumab-Fab showed relatively uniform accumulation throughout the tumor nodule. Using serial injections (19-h interval) of trastuzumab-rhodamine green and carboxytetramethylrhodamine (TAMRA), it was observed that the latterly injected trastuzumab-TAMRA was distributed more centrally than trastuzumab-rhodamine green injected first, whereas no difference was observed in the control mixed-injection group. Moreover, the mixed injection of trastuzumab and trastuzumab-Fab showed that trastuzumab-Fab distributed more centrally than the same amount of co-injected trastuzumab. Our results suggest that the strategies of increasing dose and using Fab fragments can be used to achieve a uniform antibody distribution within peritoneal disseminated nodules after intraperitoneal injection. Furthermore, serial-injection and mixed-injection strategies can modify antibody microdistribution within tumors and have the potential for preferential delivery of anticancer drugs to either the tumor periphery or its center.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19961490-12778170,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19961490-1327501,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19961490-8044785
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1349-7006
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
820-5
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19961490-Animals,
pubmed-meshheading:19961490-Antibodies, Monoclonal,
pubmed-meshheading:19961490-Antibodies, Monoclonal, Humanized,
pubmed-meshheading:19961490-Antineoplastic Agents,
pubmed-meshheading:19961490-Cell Line, Tumor,
pubmed-meshheading:19961490-Female,
pubmed-meshheading:19961490-Humans,
pubmed-meshheading:19961490-Immunoglobulin Fab Fragments,
pubmed-meshheading:19961490-Injections, Intraperitoneal,
pubmed-meshheading:19961490-Mice,
pubmed-meshheading:19961490-Microscopy, Fluorescence,
pubmed-meshheading:19961490-Ovarian Neoplasms,
pubmed-meshheading:19961490-Peritoneal Neoplasms,
pubmed-meshheading:19961490-Peritoneum,
pubmed-meshheading:19961490-Tissue Distribution
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pubmed:year |
2010
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pubmed:articleTitle |
Semiquantitative assessment of the microdistribution of fluorescence-labeled monoclonal antibody in small peritoneal disseminations of ovarian cancer.
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pubmed:affiliation |
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Intramural
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