Biodistribution and localization of radiolabeled NR-LU-10 fab fragment in human breast cancer xenografts
Radioimmunodetection, which takes advantage of tumor-specific or tumor-associated radiolabeled monoclonal antibodies or other biologic molecules to diagnose the extent of disease in cancer patients, has been of limited use in studies to date in patients with breast cancer. The difficulty is in findi...
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Veröffentlicht in: | Nuclear medicine and biology 1998-10, Vol.25 (7), p.633-637 |
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creator | Burak, William E DePalatis, Louis Nines, Ronald Hitchcock, Charles Hinkle, George Houchens, David Farrar, William B |
description | Radioimmunodetection, which takes advantage of tumor-specific or tumor-associated radiolabeled monoclonal antibodies or other biologic molecules to diagnose the extent of disease in cancer patients, has been of limited use in studies to date in patients with breast cancer. The difficulty is in finding an antibody that is both sensitive and specific enough to localize in breast tumors. This study undertook immunohistochemical and
in vivo evaluation of tumor localization and biodistribution of NR-LU-10 Fab (antibody fragment) in breast tumors to determine its ability to bind selectively to malignant tissue. NR-LU-10 Fab recognizes a pancarcinoma glycoprotein antigen found on tumors of epithelial cell origin. NR-LU-10 Fab reacted with 6/6 (100%) breast cancer cell lines and 14/16 (87.5%) breast tumors with varying degrees of immunostaining intensities. Athymic mice bearing ZR-75-1 breast cancer xenografts were injected with
125I-labeled NR-LU-10 Fab (12 μg/5 μCi) and sacrificed at fixed time intervals. These studies demonstrated the highest tumor uptake of labeled Fab at 12 h postinjection (4.58 ± 1.59% of injected dose/gram [% ID/g] of tissue); this gradually decreased to 0.13 ± 0.05% ID/g of tissue by 72 h postinjection of the radiolabeled Fab. Biolocalization to normal tissues was as predicted for a Fab fragment;
i.e., initially high in clearance organs (kidney), followed by rapid clearance over the 72-h test period. NR-LU-10 Fab displays adequate breast tumor localization with minimal biolocalization to normal tissues, thus supporting its potential use in radioimmunoscintigraphy and the RIGS® system (radioimmunoguided surgery). |
doi_str_mv | 10.1016/S0969-8051(98)00028-6 |
format | Article |
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in vivo evaluation of tumor localization and biodistribution of NR-LU-10 Fab (antibody fragment) in breast tumors to determine its ability to bind selectively to malignant tissue. NR-LU-10 Fab recognizes a pancarcinoma glycoprotein antigen found on tumors of epithelial cell origin. NR-LU-10 Fab reacted with 6/6 (100%) breast cancer cell lines and 14/16 (87.5%) breast tumors with varying degrees of immunostaining intensities. Athymic mice bearing ZR-75-1 breast cancer xenografts were injected with
125I-labeled NR-LU-10 Fab (12 μg/5 μCi) and sacrificed at fixed time intervals. These studies demonstrated the highest tumor uptake of labeled Fab at 12 h postinjection (4.58 ± 1.59% of injected dose/gram [% ID/g] of tissue); this gradually decreased to 0.13 ± 0.05% ID/g of tissue by 72 h postinjection of the radiolabeled Fab. Biolocalization to normal tissues was as predicted for a Fab fragment;
i.e., initially high in clearance organs (kidney), followed by rapid clearance over the 72-h test period. NR-LU-10 Fab displays adequate breast tumor localization with minimal biolocalization to normal tissues, thus supporting its potential use in radioimmunoscintigraphy and the RIGS® system (radioimmunoguided surgery).</description><identifier>ISSN: 0969-8051</identifier><identifier>EISSN: 1872-9614</identifier><identifier>DOI: 10.1016/S0969-8051(98)00028-6</identifier><identifier>PMID: 9804044</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Animals ; Antibodies, Monoclonal - chemistry ; Antibodies, Monoclonal - metabolism ; Antibody Specificity ; Biolocalization ; Biological and medical sciences ; Breast cancer ; Breast Neoplasms - chemistry ; Breast Neoplasms - diagnostic imaging ; Breast Neoplasms - pathology ; Disease Models, Animal ; Endocrine glands. Genital system. Mammary gland ; Female ; Humans ; Immunoglobulin Fab Fragments - chemistry ; Immunoglobulin Fab Fragments - metabolism ; Immunohistochemistry ; Investigative techniques, diagnostic techniques (general aspects) ; Lymphoma - chemistry ; Lymphoma - diagnostic imaging ; Lymphoma - pathology ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; NR-LU-10 antibody ; Radioimmunodetection - methods ; Radionuclide investigations ; Tissue Distribution - drug effects ; Tumor Cells, Cultured ; Xenografts</subject><ispartof>Nuclear medicine and biology, 1998-10, Vol.25 (7), p.633-637</ispartof><rights>1998 Elsevier Science Inc.</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-deac2ddba194dae642cf83683d2df4af9a930c63d6dac6cd426a55ea41d383223</citedby><cites>FETCH-LOGICAL-c389t-deac2ddba194dae642cf83683d2df4af9a930c63d6dac6cd426a55ea41d383223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0969805198000286$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2409743$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9804044$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Burak, William E</creatorcontrib><creatorcontrib>DePalatis, Louis</creatorcontrib><creatorcontrib>Nines, Ronald</creatorcontrib><creatorcontrib>Hitchcock, Charles</creatorcontrib><creatorcontrib>Hinkle, George</creatorcontrib><creatorcontrib>Houchens, David</creatorcontrib><creatorcontrib>Farrar, William B</creatorcontrib><title>Biodistribution and localization of radiolabeled NR-LU-10 fab fragment in human breast cancer xenografts</title><title>Nuclear medicine and biology</title><addtitle>Nucl Med Biol</addtitle><description>Radioimmunodetection, which takes advantage of tumor-specific or tumor-associated radiolabeled monoclonal antibodies or other biologic molecules to diagnose the extent of disease in cancer patients, has been of limited use in studies to date in patients with breast cancer. The difficulty is in finding an antibody that is both sensitive and specific enough to localize in breast tumors. This study undertook immunohistochemical and
in vivo evaluation of tumor localization and biodistribution of NR-LU-10 Fab (antibody fragment) in breast tumors to determine its ability to bind selectively to malignant tissue. NR-LU-10 Fab recognizes a pancarcinoma glycoprotein antigen found on tumors of epithelial cell origin. NR-LU-10 Fab reacted with 6/6 (100%) breast cancer cell lines and 14/16 (87.5%) breast tumors with varying degrees of immunostaining intensities. Athymic mice bearing ZR-75-1 breast cancer xenografts were injected with
125I-labeled NR-LU-10 Fab (12 μg/5 μCi) and sacrificed at fixed time intervals. These studies demonstrated the highest tumor uptake of labeled Fab at 12 h postinjection (4.58 ± 1.59% of injected dose/gram [% ID/g] of tissue); this gradually decreased to 0.13 ± 0.05% ID/g of tissue by 72 h postinjection of the radiolabeled Fab. Biolocalization to normal tissues was as predicted for a Fab fragment;
i.e., initially high in clearance organs (kidney), followed by rapid clearance over the 72-h test period. NR-LU-10 Fab displays adequate breast tumor localization with minimal biolocalization to normal tissues, thus supporting its potential use in radioimmunoscintigraphy and the RIGS® system (radioimmunoguided surgery).</description><subject>Animals</subject><subject>Antibodies, Monoclonal - chemistry</subject><subject>Antibodies, Monoclonal - metabolism</subject><subject>Antibody Specificity</subject><subject>Biolocalization</subject><subject>Biological and medical sciences</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - chemistry</subject><subject>Breast Neoplasms - diagnostic imaging</subject><subject>Breast Neoplasms - pathology</subject><subject>Disease Models, Animal</subject><subject>Endocrine glands. Genital system. Mammary gland</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoglobulin Fab Fragments - chemistry</subject><subject>Immunoglobulin Fab Fragments - metabolism</subject><subject>Immunohistochemistry</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Lymphoma - chemistry</subject><subject>Lymphoma - diagnostic imaging</subject><subject>Lymphoma - pathology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Neoplasm Transplantation</subject><subject>NR-LU-10 antibody</subject><subject>Radioimmunodetection - methods</subject><subject>Radionuclide investigations</subject><subject>Tissue Distribution - drug effects</subject><subject>Tumor Cells, Cultured</subject><subject>Xenografts</subject><issn>0969-8051</issn><issn>1872-9614</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1vFDEMhiMEKkvhJ1TKAaFymJKvzSYnBBUflVYgAT1HnsRpg2YmJZlBhV9PurvaKydL9vPa1kPIGWcXnHH95juz2naGrfm5Na8ZY8J0-hFZcbMRndVcPSarI_KUPKv1J2s5xdkJObGGKabUity-TzmkOpfUL3PKE4Up0CF7GNJf2DVypAVCygP0OGCgX7512-uOMxqhp7HAzYjTTNNEb5cRJtoXhDpTD5PHQu9xyjcF4lyfkycRhoovDvWUXH_88OPyc7f9-unq8t2289LYuQsIXoTQA7cqAGolfDRSGxlEiAqiBSuZ1zLoAF77oISG9RpB8SCNFEKeklf7vXcl_1qwzm5M1eMwwIR5qW7TRGm7A9d70Jdca8Ho7koaofxxnLkHw25n2D3oc9a4nWGnW-7scGDpRwzH1EFpm788zKE2jc3Q5FM9YkIxu1GyYW_3GDYZvxMWV33CJi2kgn52Iaf_PPIPvoqZDw</recordid><startdate>19981001</startdate><enddate>19981001</enddate><creator>Burak, William E</creator><creator>DePalatis, Louis</creator><creator>Nines, Ronald</creator><creator>Hitchcock, Charles</creator><creator>Hinkle, George</creator><creator>Houchens, David</creator><creator>Farrar, William B</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19981001</creationdate><title>Biodistribution and localization of radiolabeled NR-LU-10 fab fragment in human breast cancer xenografts</title><author>Burak, William E ; DePalatis, Louis ; Nines, Ronald ; Hitchcock, Charles ; Hinkle, George ; Houchens, David ; Farrar, William B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-deac2ddba194dae642cf83683d2df4af9a930c63d6dac6cd426a55ea41d383223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - chemistry</topic><topic>Antibodies, Monoclonal - metabolism</topic><topic>Antibody Specificity</topic><topic>Biolocalization</topic><topic>Biological and medical sciences</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - chemistry</topic><topic>Breast Neoplasms - diagnostic imaging</topic><topic>Breast Neoplasms - pathology</topic><topic>Disease Models, Animal</topic><topic>Endocrine glands. Genital system. Mammary gland</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoglobulin Fab Fragments - chemistry</topic><topic>Immunoglobulin Fab Fragments - metabolism</topic><topic>Immunohistochemistry</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Lymphoma - chemistry</topic><topic>Lymphoma - diagnostic imaging</topic><topic>Lymphoma - pathology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Neoplasm Transplantation</topic><topic>NR-LU-10 antibody</topic><topic>Radioimmunodetection - methods</topic><topic>Radionuclide investigations</topic><topic>Tissue Distribution - drug effects</topic><topic>Tumor Cells, Cultured</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Burak, William E</creatorcontrib><creatorcontrib>DePalatis, Louis</creatorcontrib><creatorcontrib>Nines, Ronald</creatorcontrib><creatorcontrib>Hitchcock, Charles</creatorcontrib><creatorcontrib>Hinkle, George</creatorcontrib><creatorcontrib>Houchens, David</creatorcontrib><creatorcontrib>Farrar, William B</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Nuclear medicine and biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Burak, William E</au><au>DePalatis, Louis</au><au>Nines, Ronald</au><au>Hitchcock, Charles</au><au>Hinkle, George</au><au>Houchens, David</au><au>Farrar, William B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biodistribution and localization of radiolabeled NR-LU-10 fab fragment in human breast cancer xenografts</atitle><jtitle>Nuclear medicine and biology</jtitle><addtitle>Nucl Med Biol</addtitle><date>1998-10-01</date><risdate>1998</risdate><volume>25</volume><issue>7</issue><spage>633</spage><epage>637</epage><pages>633-637</pages><issn>0969-8051</issn><eissn>1872-9614</eissn><abstract>Radioimmunodetection, which takes advantage of tumor-specific or tumor-associated radiolabeled monoclonal antibodies or other biologic molecules to diagnose the extent of disease in cancer patients, has been of limited use in studies to date in patients with breast cancer. The difficulty is in finding an antibody that is both sensitive and specific enough to localize in breast tumors. This study undertook immunohistochemical and
in vivo evaluation of tumor localization and biodistribution of NR-LU-10 Fab (antibody fragment) in breast tumors to determine its ability to bind selectively to malignant tissue. NR-LU-10 Fab recognizes a pancarcinoma glycoprotein antigen found on tumors of epithelial cell origin. NR-LU-10 Fab reacted with 6/6 (100%) breast cancer cell lines and 14/16 (87.5%) breast tumors with varying degrees of immunostaining intensities. Athymic mice bearing ZR-75-1 breast cancer xenografts were injected with
125I-labeled NR-LU-10 Fab (12 μg/5 μCi) and sacrificed at fixed time intervals. These studies demonstrated the highest tumor uptake of labeled Fab at 12 h postinjection (4.58 ± 1.59% of injected dose/gram [% ID/g] of tissue); this gradually decreased to 0.13 ± 0.05% ID/g of tissue by 72 h postinjection of the radiolabeled Fab. Biolocalization to normal tissues was as predicted for a Fab fragment;
i.e., initially high in clearance organs (kidney), followed by rapid clearance over the 72-h test period. NR-LU-10 Fab displays adequate breast tumor localization with minimal biolocalization to normal tissues, thus supporting its potential use in radioimmunoscintigraphy and the RIGS® system (radioimmunoguided surgery).</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>9804044</pmid><doi>10.1016/S0969-8051(98)00028-6</doi><tpages>5</tpages></addata></record> |
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subjects | Animals Antibodies, Monoclonal - chemistry Antibodies, Monoclonal - metabolism Antibody Specificity Biolocalization Biological and medical sciences Breast cancer Breast Neoplasms - chemistry Breast Neoplasms - diagnostic imaging Breast Neoplasms - pathology Disease Models, Animal Endocrine glands. Genital system. Mammary gland Female Humans Immunoglobulin Fab Fragments - chemistry Immunoglobulin Fab Fragments - metabolism Immunohistochemistry Investigative techniques, diagnostic techniques (general aspects) Lymphoma - chemistry Lymphoma - diagnostic imaging Lymphoma - pathology Medical sciences Mice Mice, Inbred BALB C Mice, Nude Neoplasm Transplantation NR-LU-10 antibody Radioimmunodetection - methods Radionuclide investigations Tissue Distribution - drug effects Tumor Cells, Cultured Xenografts |
title | Biodistribution and localization of radiolabeled NR-LU-10 fab fragment in human breast cancer xenografts |
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