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Molecular Targeting and Treatment of an Epidermal Growth Factor Receptor–Positive Glioma Using Boronated Cetuximab
Purpose: The purpose of the present study was to evaluate the anti–epidermal growth factor monoclonal antibody (mAb) cetuximab (IMC-C225) as a delivery agent for boron neutron capture therapy (BNCT) of a human epidermal growth factor receptor (EGFR) gene-transfected rat glioma, designated as F98 EGF...
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| Published in: | Clinical cancer research 2007-02, Vol.13 (4), p.1260-1268 |
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| container_end_page | 1268 |
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| container_title | Clinical cancer research |
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| creator | GONG WU WEILIAN YANG MING YANG CHRISTOFORIDIS, Gregory A SFERRA, Thomas J BINNS, Peter J RILEY, Kent J CIESIELSKI, Michael J FENSTERMAKER, Robert A BARTH, Rolf F KAWABATA, Shinji SWINDALL, Michele BANDYOPADHYAYA, Achintya K TJARKS, Werner KHORSANDI, Behrooz BLUE, Thomas E FERKETICH, Amy K |
| description | Purpose: The purpose of the present study was to evaluate the anti–epidermal growth factor monoclonal antibody (mAb) cetuximab (IMC-C225)
as a delivery agent for boron neutron capture therapy (BNCT) of a human epidermal growth factor receptor (EGFR) gene-transfected
rat glioma, designated as F98 EGFR .
Experimental Design: A heavily boronated polyamidoamine dendrimer was chemically linked to cetuximab by means of the heterobifunctional reagents
N -succinimidyl 3-(2-pyridyldithio)-propionate and N -(k-maleimido undecanoic acid)-hydrazide. The bioconjugate, designated as BD-C225, was specifically taken up by F98 EGFR glioma cells in vitro compared with receptor-negative F98 wild-type cells (41.8 versus 9.1 μg/g). For in vivo biodistribution studies, F98 EGFR cells were implanted stereotactically into the brains of Fischer rats, and 14 days later, BD-C225 was given intracerebrally
by either convection enhanced delivery (CED) or direct intratumoral (i.t.) injection.
Results: The amount of boron retained by F98 EGFR gliomas 24 h following CED or i.t. injection was 77.2 and 50.8 μg/g, respectively, with normal brain and blood boron values |
| doi_str_mv | 10.1158/1078-0432.CCR-06-2399 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69040245</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20283610</sourcerecordid><originalsourceid>FETCH-LOGICAL-c618t-f7ee4507030a06c11e04aa3166528083e5a487cc522cfaf086e638ab33b201ca3</originalsourceid><addsrcrecordid>eNqFkcFu1DAQhiMEoqXwCCBfQL2kjO3Y8R5p1C5IRaBqe7ZmvZNdoyRebIfCre_AG_IkJNpFPXKaX6Nv_tHMXxSvOVxwrsx7DrUpoZLiomluS9ClkIvFk-KUK1WXUmj1dNL_mJPiRUrfAHjFoXpenPBa8tpIc1rkz6EjN3YY2QrjlrIftgyHDVtFwtzTkFlopwa72vsNxR47tozhPu_YNbocIrslR_tJ_Hn4_TUkn_0PYsvOhx7ZXZrNLkMMA2basIby-NP3uH5ZPGuxS_TqWM-Ku-urVfOxvPmy_NR8uCmd5iaXbU1UKahBAoJ2nBNUiJJrrYQBI0lhZWrnlBCuxRaMJi0NrqVcC-AO5Vnx7uC7j-H7SCnb3idHXYcDhTFZvYAKRKX-CwoQRmoOE6gOoIshpUit3cfpovjLcrBzLnb-uZ1_bqdcLGg75zLNvTkuGNc9bR6njkFMwNsjgMlh10YcnE-PnKkBQMxG5wdu57e7ex_JuomkGCkRRrezXNrKcqFB_gUmX6Uz</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20283610</pqid></control><display><type>article</type><title>Molecular Targeting and Treatment of an Epidermal Growth Factor Receptor–Positive Glioma Using Boronated Cetuximab</title><source>Freely Accessible Science Journals</source><creator>GONG WU ; WEILIAN YANG ; MING YANG ; CHRISTOFORIDIS, Gregory A ; SFERRA, Thomas J ; BINNS, Peter J ; RILEY, Kent J ; CIESIELSKI, Michael J ; FENSTERMAKER, Robert A ; BARTH, Rolf F ; KAWABATA, Shinji ; SWINDALL, Michele ; BANDYOPADHYAYA, Achintya K ; TJARKS, Werner ; KHORSANDI, Behrooz ; BLUE, Thomas E ; FERKETICH, Amy K</creator><creatorcontrib>GONG WU ; WEILIAN YANG ; MING YANG ; CHRISTOFORIDIS, Gregory A ; SFERRA, Thomas J ; BINNS, Peter J ; RILEY, Kent J ; CIESIELSKI, Michael J ; FENSTERMAKER, Robert A ; BARTH, Rolf F ; KAWABATA, Shinji ; SWINDALL, Michele ; BANDYOPADHYAYA, Achintya K ; TJARKS, Werner ; KHORSANDI, Behrooz ; BLUE, Thomas E ; FERKETICH, Amy K</creatorcontrib><description>Purpose: The purpose of the present study was to evaluate the anti–epidermal growth factor monoclonal antibody (mAb) cetuximab (IMC-C225)
as a delivery agent for boron neutron capture therapy (BNCT) of a human epidermal growth factor receptor (EGFR) gene-transfected
rat glioma, designated as F98 EGFR .
Experimental Design: A heavily boronated polyamidoamine dendrimer was chemically linked to cetuximab by means of the heterobifunctional reagents
N -succinimidyl 3-(2-pyridyldithio)-propionate and N -(k-maleimido undecanoic acid)-hydrazide. The bioconjugate, designated as BD-C225, was specifically taken up by F98 EGFR glioma cells in vitro compared with receptor-negative F98 wild-type cells (41.8 versus 9.1 μg/g). For in vivo biodistribution studies, F98 EGFR cells were implanted stereotactically into the brains of Fischer rats, and 14 days later, BD-C225 was given intracerebrally
by either convection enhanced delivery (CED) or direct intratumoral (i.t.) injection.
Results: The amount of boron retained by F98 EGFR gliomas 24 h following CED or i.t. injection was 77.2 and 50.8 μg/g, respectively, with normal brain and blood boron values
<0.05 μg/g. Boron neutron capture therapy was carried out at the Massachusetts Institute of Technology Research Reactor 24
h after CED of BD-C225, either alone or in combination with i.v. boronophenylalanine (BPA). The corresponding mean survival
times (MST) were 54.5 and 70.9 days ( P = 0.017), respectively, with one long-term survivor (more than 180 days). In contrast, the MSTs of irradiated and untreated
controls, respectively, were 30.3 and 26.3 days. In a second study, the combination of BD-C225 and BPA plus sodium borocaptate,
given by either i.v. or intracarotid injection, was evaluated and the MSTs were equivalent to that obtained with BD-C225 plus
i.v. BPA.
Conclusions: The survival data obtained with BD-C225 are comparable with those recently reported by us using boronated mAb L8A4 as the
delivery agent. This mAb recognizes the mutant receptor, EGFRvIII. Taken together, these data convincingly show the therapeutic
efficacy of molecular targeting of EGFR using a boronated mAb either alone or in combination with BPA and provide a platform
for the future development of combinations of high and low molecular weight delivery agents for BNCT of brain tumors.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-06-2399</identifier><identifier>PMID: 17317838</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Antibodies, Monoclonal - chemistry ; Antibodies, Monoclonal - immunology ; Antibodies, Monoclonal - pharmacokinetics ; Antibodies, Monoclonal - pharmacology ; Antibodies, Monoclonal, Humanized ; Antineoplastic agents ; Biological and medical sciences ; Boron Compounds - administration & dosage ; Boron Compounds - chemistry ; Boron Compounds - pharmacokinetics ; Boron Neutron Capture Therapy - methods ; boronated cetuximab ; Cetuximab ; Combined Modality Therapy ; Dendrimers - administration & dosage ; Dendrimers - chemistry ; Dendrimers - pharmacokinetics ; EGFR ; F98 ; Glioma - drug therapy ; Glioma - metabolism ; Glioma - radiotherapy ; Humans ; Immunoconjugates - pharmacokinetics ; Immunoconjugates - pharmacology ; Magnetic Resonance Imaging - methods ; Medical sciences ; Neurology ; neutron capture therapy ; Pharmacology. Drug treatments ; rat glioma ; Rats ; Rats, Inbred F344 ; Receptor, Epidermal Growth Factor - biosynthesis ; Receptor, Epidermal Growth Factor - immunology ; Receptor, Epidermal Growth Factor - metabolism ; Tissue Distribution ; Tumors of the nervous system. Phacomatoses</subject><ispartof>Clinical cancer research, 2007-02, Vol.13 (4), p.1260-1268</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c618t-f7ee4507030a06c11e04aa3166528083e5a487cc522cfaf086e638ab33b201ca3</citedby><cites>FETCH-LOGICAL-c618t-f7ee4507030a06c11e04aa3166528083e5a487cc522cfaf086e638ab33b201ca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18700029$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17317838$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GONG WU</creatorcontrib><creatorcontrib>WEILIAN YANG</creatorcontrib><creatorcontrib>MING YANG</creatorcontrib><creatorcontrib>CHRISTOFORIDIS, Gregory A</creatorcontrib><creatorcontrib>SFERRA, Thomas J</creatorcontrib><creatorcontrib>BINNS, Peter J</creatorcontrib><creatorcontrib>RILEY, Kent J</creatorcontrib><creatorcontrib>CIESIELSKI, Michael J</creatorcontrib><creatorcontrib>FENSTERMAKER, Robert A</creatorcontrib><creatorcontrib>BARTH, Rolf F</creatorcontrib><creatorcontrib>KAWABATA, Shinji</creatorcontrib><creatorcontrib>SWINDALL, Michele</creatorcontrib><creatorcontrib>BANDYOPADHYAYA, Achintya K</creatorcontrib><creatorcontrib>TJARKS, Werner</creatorcontrib><creatorcontrib>KHORSANDI, Behrooz</creatorcontrib><creatorcontrib>BLUE, Thomas E</creatorcontrib><creatorcontrib>FERKETICH, Amy K</creatorcontrib><title>Molecular Targeting and Treatment of an Epidermal Growth Factor Receptor–Positive Glioma Using Boronated Cetuximab</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: The purpose of the present study was to evaluate the anti–epidermal growth factor monoclonal antibody (mAb) cetuximab (IMC-C225)
as a delivery agent for boron neutron capture therapy (BNCT) of a human epidermal growth factor receptor (EGFR) gene-transfected
rat glioma, designated as F98 EGFR .
Experimental Design: A heavily boronated polyamidoamine dendrimer was chemically linked to cetuximab by means of the heterobifunctional reagents
N -succinimidyl 3-(2-pyridyldithio)-propionate and N -(k-maleimido undecanoic acid)-hydrazide. The bioconjugate, designated as BD-C225, was specifically taken up by F98 EGFR glioma cells in vitro compared with receptor-negative F98 wild-type cells (41.8 versus 9.1 μg/g). For in vivo biodistribution studies, F98 EGFR cells were implanted stereotactically into the brains of Fischer rats, and 14 days later, BD-C225 was given intracerebrally
by either convection enhanced delivery (CED) or direct intratumoral (i.t.) injection.
Results: The amount of boron retained by F98 EGFR gliomas 24 h following CED or i.t. injection was 77.2 and 50.8 μg/g, respectively, with normal brain and blood boron values
<0.05 μg/g. Boron neutron capture therapy was carried out at the Massachusetts Institute of Technology Research Reactor 24
h after CED of BD-C225, either alone or in combination with i.v. boronophenylalanine (BPA). The corresponding mean survival
times (MST) were 54.5 and 70.9 days ( P = 0.017), respectively, with one long-term survivor (more than 180 days). In contrast, the MSTs of irradiated and untreated
controls, respectively, were 30.3 and 26.3 days. In a second study, the combination of BD-C225 and BPA plus sodium borocaptate,
given by either i.v. or intracarotid injection, was evaluated and the MSTs were equivalent to that obtained with BD-C225 plus
i.v. BPA.
Conclusions: The survival data obtained with BD-C225 are comparable with those recently reported by us using boronated mAb L8A4 as the
delivery agent. This mAb recognizes the mutant receptor, EGFRvIII. Taken together, these data convincingly show the therapeutic
efficacy of molecular targeting of EGFR using a boronated mAb either alone or in combination with BPA and provide a platform
for the future development of combinations of high and low molecular weight delivery agents for BNCT of brain tumors.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - chemistry</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Monoclonal - pharmacokinetics</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antibodies, Monoclonal, Humanized</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Boron Compounds - administration & dosage</subject><subject>Boron Compounds - chemistry</subject><subject>Boron Compounds - pharmacokinetics</subject><subject>Boron Neutron Capture Therapy - methods</subject><subject>boronated cetuximab</subject><subject>Cetuximab</subject><subject>Combined Modality Therapy</subject><subject>Dendrimers - administration & dosage</subject><subject>Dendrimers - chemistry</subject><subject>Dendrimers - pharmacokinetics</subject><subject>EGFR</subject><subject>F98</subject><subject>Glioma - drug therapy</subject><subject>Glioma - metabolism</subject><subject>Glioma - radiotherapy</subject><subject>Humans</subject><subject>Immunoconjugates - pharmacokinetics</subject><subject>Immunoconjugates - pharmacology</subject><subject>Magnetic Resonance Imaging - methods</subject><subject>Medical sciences</subject><subject>Neurology</subject><subject>neutron capture therapy</subject><subject>Pharmacology. Drug treatments</subject><subject>rat glioma</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Receptor, Epidermal Growth Factor - biosynthesis</subject><subject>Receptor, Epidermal Growth Factor - immunology</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>Tissue Distribution</subject><subject>Tumors of the nervous system. Phacomatoses</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNqFkcFu1DAQhiMEoqXwCCBfQL2kjO3Y8R5p1C5IRaBqe7ZmvZNdoyRebIfCre_AG_IkJNpFPXKaX6Nv_tHMXxSvOVxwrsx7DrUpoZLiomluS9ClkIvFk-KUK1WXUmj1dNL_mJPiRUrfAHjFoXpenPBa8tpIc1rkz6EjN3YY2QrjlrIftgyHDVtFwtzTkFlopwa72vsNxR47tozhPu_YNbocIrslR_tJ_Hn4_TUkn_0PYsvOhx7ZXZrNLkMMA2basIby-NP3uH5ZPGuxS_TqWM-Ku-urVfOxvPmy_NR8uCmd5iaXbU1UKahBAoJ2nBNUiJJrrYQBI0lhZWrnlBCuxRaMJi0NrqVcC-AO5Vnx7uC7j-H7SCnb3idHXYcDhTFZvYAKRKX-CwoQRmoOE6gOoIshpUit3cfpovjLcrBzLnb-uZ1_bqdcLGg75zLNvTkuGNc9bR6njkFMwNsjgMlh10YcnE-PnKkBQMxG5wdu57e7ex_JuomkGCkRRrezXNrKcqFB_gUmX6Uz</recordid><startdate>20070215</startdate><enddate>20070215</enddate><creator>GONG WU</creator><creator>WEILIAN YANG</creator><creator>MING YANG</creator><creator>CHRISTOFORIDIS, Gregory A</creator><creator>SFERRA, Thomas J</creator><creator>BINNS, Peter J</creator><creator>RILEY, Kent J</creator><creator>CIESIELSKI, Michael J</creator><creator>FENSTERMAKER, Robert A</creator><creator>BARTH, Rolf F</creator><creator>KAWABATA, Shinji</creator><creator>SWINDALL, Michele</creator><creator>BANDYOPADHYAYA, Achintya K</creator><creator>TJARKS, Werner</creator><creator>KHORSANDI, Behrooz</creator><creator>BLUE, Thomas E</creator><creator>FERKETICH, Amy K</creator><general>American Association for Cancer Research</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>7TK</scope><scope>7X8</scope></search><sort><creationdate>20070215</creationdate><title>Molecular Targeting and Treatment of an Epidermal Growth Factor Receptor–Positive Glioma Using Boronated Cetuximab</title><author>GONG WU ; WEILIAN YANG ; MING YANG ; CHRISTOFORIDIS, Gregory A ; SFERRA, Thomas J ; BINNS, Peter J ; RILEY, Kent J ; CIESIELSKI, Michael J ; FENSTERMAKER, Robert A ; BARTH, Rolf F ; KAWABATA, Shinji ; SWINDALL, Michele ; BANDYOPADHYAYA, Achintya K ; TJARKS, Werner ; KHORSANDI, Behrooz ; BLUE, Thomas E ; FERKETICH, Amy K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c618t-f7ee4507030a06c11e04aa3166528083e5a487cc522cfaf086e638ab33b201ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - chemistry</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibodies, Monoclonal - pharmacokinetics</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Antibodies, Monoclonal, Humanized</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Boron Compounds - administration & dosage</topic><topic>Boron Compounds - chemistry</topic><topic>Boron Compounds - pharmacokinetics</topic><topic>Boron Neutron Capture Therapy - methods</topic><topic>boronated cetuximab</topic><topic>Cetuximab</topic><topic>Combined Modality Therapy</topic><topic>Dendrimers - administration & dosage</topic><topic>Dendrimers - chemistry</topic><topic>Dendrimers - pharmacokinetics</topic><topic>EGFR</topic><topic>F98</topic><topic>Glioma - drug therapy</topic><topic>Glioma - metabolism</topic><topic>Glioma - radiotherapy</topic><topic>Humans</topic><topic>Immunoconjugates - pharmacokinetics</topic><topic>Immunoconjugates - pharmacology</topic><topic>Magnetic Resonance Imaging - methods</topic><topic>Medical sciences</topic><topic>Neurology</topic><topic>neutron capture therapy</topic><topic>Pharmacology. Drug treatments</topic><topic>rat glioma</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Receptor, Epidermal Growth Factor - biosynthesis</topic><topic>Receptor, Epidermal Growth Factor - immunology</topic><topic>Receptor, Epidermal Growth Factor - metabolism</topic><topic>Tissue Distribution</topic><topic>Tumors of the nervous system. Phacomatoses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GONG WU</creatorcontrib><creatorcontrib>WEILIAN YANG</creatorcontrib><creatorcontrib>MING YANG</creatorcontrib><creatorcontrib>CHRISTOFORIDIS, Gregory A</creatorcontrib><creatorcontrib>SFERRA, Thomas J</creatorcontrib><creatorcontrib>BINNS, Peter J</creatorcontrib><creatorcontrib>RILEY, Kent J</creatorcontrib><creatorcontrib>CIESIELSKI, Michael J</creatorcontrib><creatorcontrib>FENSTERMAKER, Robert A</creatorcontrib><creatorcontrib>BARTH, Rolf F</creatorcontrib><creatorcontrib>KAWABATA, Shinji</creatorcontrib><creatorcontrib>SWINDALL, Michele</creatorcontrib><creatorcontrib>BANDYOPADHYAYA, Achintya K</creatorcontrib><creatorcontrib>TJARKS, Werner</creatorcontrib><creatorcontrib>KHORSANDI, Behrooz</creatorcontrib><creatorcontrib>BLUE, Thomas E</creatorcontrib><creatorcontrib>FERKETICH, Amy K</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>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GONG WU</au><au>WEILIAN YANG</au><au>MING YANG</au><au>CHRISTOFORIDIS, Gregory A</au><au>SFERRA, Thomas J</au><au>BINNS, Peter J</au><au>RILEY, Kent J</au><au>CIESIELSKI, Michael J</au><au>FENSTERMAKER, Robert A</au><au>BARTH, Rolf F</au><au>KAWABATA, Shinji</au><au>SWINDALL, Michele</au><au>BANDYOPADHYAYA, Achintya K</au><au>TJARKS, Werner</au><au>KHORSANDI, Behrooz</au><au>BLUE, Thomas E</au><au>FERKETICH, Amy K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular Targeting and Treatment of an Epidermal Growth Factor Receptor–Positive Glioma Using Boronated Cetuximab</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2007-02-15</date><risdate>2007</risdate><volume>13</volume><issue>4</issue><spage>1260</spage><epage>1268</epage><pages>1260-1268</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: The purpose of the present study was to evaluate the anti–epidermal growth factor monoclonal antibody (mAb) cetuximab (IMC-C225)
as a delivery agent for boron neutron capture therapy (BNCT) of a human epidermal growth factor receptor (EGFR) gene-transfected
rat glioma, designated as F98 EGFR .
Experimental Design: A heavily boronated polyamidoamine dendrimer was chemically linked to cetuximab by means of the heterobifunctional reagents
N -succinimidyl 3-(2-pyridyldithio)-propionate and N -(k-maleimido undecanoic acid)-hydrazide. The bioconjugate, designated as BD-C225, was specifically taken up by F98 EGFR glioma cells in vitro compared with receptor-negative F98 wild-type cells (41.8 versus 9.1 μg/g). For in vivo biodistribution studies, F98 EGFR cells were implanted stereotactically into the brains of Fischer rats, and 14 days later, BD-C225 was given intracerebrally
by either convection enhanced delivery (CED) or direct intratumoral (i.t.) injection.
Results: The amount of boron retained by F98 EGFR gliomas 24 h following CED or i.t. injection was 77.2 and 50.8 μg/g, respectively, with normal brain and blood boron values
<0.05 μg/g. Boron neutron capture therapy was carried out at the Massachusetts Institute of Technology Research Reactor 24
h after CED of BD-C225, either alone or in combination with i.v. boronophenylalanine (BPA). The corresponding mean survival
times (MST) were 54.5 and 70.9 days ( P = 0.017), respectively, with one long-term survivor (more than 180 days). In contrast, the MSTs of irradiated and untreated
controls, respectively, were 30.3 and 26.3 days. In a second study, the combination of BD-C225 and BPA plus sodium borocaptate,
given by either i.v. or intracarotid injection, was evaluated and the MSTs were equivalent to that obtained with BD-C225 plus
i.v. BPA.
Conclusions: The survival data obtained with BD-C225 are comparable with those recently reported by us using boronated mAb L8A4 as the
delivery agent. This mAb recognizes the mutant receptor, EGFRvIII. Taken together, these data convincingly show the therapeutic
efficacy of molecular targeting of EGFR using a boronated mAb either alone or in combination with BPA and provide a platform
for the future development of combinations of high and low molecular weight delivery agents for BNCT of brain tumors.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>17317838</pmid><doi>10.1158/1078-0432.CCR-06-2399</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 2007-02, Vol.13 (4), p.1260-1268 |
| issn | 1078-0432 1557-3265 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_69040245 |
| source | Freely Accessible Science Journals |
| subjects | Animals Antibodies, Monoclonal - chemistry Antibodies, Monoclonal - immunology Antibodies, Monoclonal - pharmacokinetics Antibodies, Monoclonal - pharmacology Antibodies, Monoclonal, Humanized Antineoplastic agents Biological and medical sciences Boron Compounds - administration & dosage Boron Compounds - chemistry Boron Compounds - pharmacokinetics Boron Neutron Capture Therapy - methods boronated cetuximab Cetuximab Combined Modality Therapy Dendrimers - administration & dosage Dendrimers - chemistry Dendrimers - pharmacokinetics EGFR F98 Glioma - drug therapy Glioma - metabolism Glioma - radiotherapy Humans Immunoconjugates - pharmacokinetics Immunoconjugates - pharmacology Magnetic Resonance Imaging - methods Medical sciences Neurology neutron capture therapy Pharmacology. Drug treatments rat glioma Rats Rats, Inbred F344 Receptor, Epidermal Growth Factor - biosynthesis Receptor, Epidermal Growth Factor - immunology Receptor, Epidermal Growth Factor - metabolism Tissue Distribution Tumors of the nervous system. Phacomatoses |
| title | Molecular Targeting and Treatment of an Epidermal Growth Factor Receptor–Positive Glioma Using Boronated Cetuximab |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T13%3A21%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Molecular%20Targeting%20and%20Treatment%20of%20an%20Epidermal%20Growth%20Factor%20Receptor%E2%80%93Positive%20Glioma%20Using%20Boronated%20Cetuximab&rft.jtitle=Clinical%20cancer%20research&rft.au=GONG%20WU&rft.date=2007-02-15&rft.volume=13&rft.issue=4&rft.spage=1260&rft.epage=1268&rft.pages=1260-1268&rft.issn=1078-0432&rft.eissn=1557-3265&rft_id=info:doi/10.1158/1078-0432.CCR-06-2399&rft_dat=%3Cproquest_cross%3E20283610%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c618t-f7ee4507030a06c11e04aa3166528083e5a487cc522cfaf086e638ab33b201ca3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=20283610&rft_id=info:pmid/17317838&rfr_iscdi=true |