Peripheral and central nervous system distribution of the CGRP neutralizing antibody [125I] galcanezumab in male rats
Objective The objective of this investigation was to examine the distribution of galcanezumab and a control immunoglobulin 4 antibody containing the same constant regions as galcanezumab, into peripheral and central tissues. Methods Galcanezumab and a control immunoglobulin 4 antibody were radioiodi...
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| Veröffentlicht in: | Cephalalgia 2019-09, Vol.39 (10), p.1241-1248 |
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| creator | Johnson, Kirk W Morin, S Michelle Wroblewski, Victor J Johnson, Michael P |
| description | Objective
The objective of this investigation was to examine the distribution of galcanezumab and a control immunoglobulin 4 antibody containing the same constant regions as galcanezumab, into peripheral and central tissues.
Methods
Galcanezumab and a control immunoglobulin 4 antibody were radioiodinated with Iodine-125 to specific activities of 0.11 mCi/mg and 0.16 mCi/mg, respectively. At 24, 72, and 168 hours following subcutaneous injection of either antibody (4 mg/kg), cerebrospinal fluid and plasma were obtained followed by saline perfusion to remove residual blood and collection of selected tissues for determination of Iodine-125 content by gamma counting.
Results
The peak plasma levels of Iodine-125 galcanezumab and Iodine-125 control immunoglobulin 4 were observed at 72 hours and remained high at 168 hours post-dose. The rank order of tissue levels was dura mater = spleen > trigeminal ganglia ≫hypothalamus = spinal cord = prefrontal cortex = cerebellum. Iodine-125 galcanezumab levels in peripheral tissue (dura mater, spleen, and trigeminal ganglia) averaged 5% to 11% of plasma, whereas all of the central nervous system (CNS) tissue levels and the cerebrospinal fluid levels were |
| doi_str_mv | 10.1177/0333102419844711 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_AFRWT</sourceid><recordid>TN_cdi_proquest_miscellaneous_2211948643</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_0333102419844711</sage_id><sourcerecordid>2211948643</sourcerecordid><originalsourceid>FETCH-LOGICAL-c337t-2bf0216ade8ec4dcf5db00794261405e4ae647a1b39146dafc8c6660ab08a2243</originalsourceid><addsrcrecordid>eNp1kEtLxDAUhYMozvjYu5Is3VTzapouZdBxYEARXYmUNL0dI32MSSrM_HpTRl0Iru6F-53DPQehM0ouKc2yK8I5p4QJmishMkr30JQKqRKWK7aPpuM5Ge8TdOT9OyEklUQeokkUEZ4qNUXDAzi7fgOnG6y7Chvowrh34D77wWO_8QFaXFkfnC2HYPsO9zUOb4Bn88eHyA0jb7e2W0WDYMu-2uAXytLFK17pxugOtkOrS2w73OoGsNPBn6CDWjceTr_nMXq-vXma3SXL-_lidr1MDOdZSFhZE0alrkCBEZWp06okJMsFk1SQFIQGKTJNS57H2JWujTJSSqJLojRjgh-ji53v2vUfA_hQtNYbaJr4VUxXMEZpLpQUPKJkhxrXe--gLtbOttptCkqKsezib9lRcv7tPpQtVL-Cn3YjkOwAr1dQvPeD62La_w2_AOy8h0c</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2211948643</pqid></control><display><type>article</type><title>Peripheral and central nervous system distribution of the CGRP neutralizing antibody [125I] galcanezumab in male rats</title><source>Sage Journals GOLD Open Access 2024</source><creator>Johnson, Kirk W ; Morin, S Michelle ; Wroblewski, Victor J ; Johnson, Michael P</creator><creatorcontrib>Johnson, Kirk W ; Morin, S Michelle ; Wroblewski, Victor J ; Johnson, Michael P</creatorcontrib><description>Objective
The objective of this investigation was to examine the distribution of galcanezumab and a control immunoglobulin 4 antibody containing the same constant regions as galcanezumab, into peripheral and central tissues.
Methods
Galcanezumab and a control immunoglobulin 4 antibody were radioiodinated with Iodine-125 to specific activities of 0.11 mCi/mg and 0.16 mCi/mg, respectively. At 24, 72, and 168 hours following subcutaneous injection of either antibody (4 mg/kg), cerebrospinal fluid and plasma were obtained followed by saline perfusion to remove residual blood and collection of selected tissues for determination of Iodine-125 content by gamma counting.
Results
The peak plasma levels of Iodine-125 galcanezumab and Iodine-125 control immunoglobulin 4 were observed at 72 hours and remained high at 168 hours post-dose. The rank order of tissue levels was dura mater = spleen > trigeminal ganglia ≫hypothalamus = spinal cord = prefrontal cortex = cerebellum. Iodine-125 galcanezumab levels in peripheral tissue (dura mater, spleen, and trigeminal ganglia) averaged 5% to 11% of plasma, whereas all of the central nervous system (CNS) tissue levels and the cerebrospinal fluid levels were < 0.4% of plasma. Distribution of the antibodies into the dura mater and the trigeminal ganglia was similar to that observed in the spleen and significantly greater than exposure in the brain or spinal cord.
Conclusions
The central levels of galcanezumab were relatively low, which would favor the dura mater and trigeminal ganglia as sites of action for its observed clinical efficacy. However, a central site of action cannot be excluded.</description><identifier>ISSN: 0333-1024</identifier><identifier>EISSN: 1468-2982</identifier><identifier>DOI: 10.1177/0333102419844711</identifier><identifier>PMID: 31003588</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><ispartof>Cephalalgia, 2019-09, Vol.39 (10), p.1241-1248</ispartof><rights>International Headache Society 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c337t-2bf0216ade8ec4dcf5db00794261405e4ae647a1b39146dafc8c6660ab08a2243</citedby><cites>FETCH-LOGICAL-c337t-2bf0216ade8ec4dcf5db00794261405e4ae647a1b39146dafc8c6660ab08a2243</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0333102419844711$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0333102419844711$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,21945,27830,27901,27902,44921,45309</link.rule.ids><linktorsrc>$$Uhttps://journals.sagepub.com/doi/full/10.1177/0333102419844711?utm_source=summon&utm_medium=discovery-provider$$EView_record_in_SAGE_Publications$$FView_record_in_$$GSAGE_Publications</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31003588$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Johnson, Kirk W</creatorcontrib><creatorcontrib>Morin, S Michelle</creatorcontrib><creatorcontrib>Wroblewski, Victor J</creatorcontrib><creatorcontrib>Johnson, Michael P</creatorcontrib><title>Peripheral and central nervous system distribution of the CGRP neutralizing antibody [125I] galcanezumab in male rats</title><title>Cephalalgia</title><addtitle>Cephalalgia</addtitle><description>Objective
The objective of this investigation was to examine the distribution of galcanezumab and a control immunoglobulin 4 antibody containing the same constant regions as galcanezumab, into peripheral and central tissues.
Methods
Galcanezumab and a control immunoglobulin 4 antibody were radioiodinated with Iodine-125 to specific activities of 0.11 mCi/mg and 0.16 mCi/mg, respectively. At 24, 72, and 168 hours following subcutaneous injection of either antibody (4 mg/kg), cerebrospinal fluid and plasma were obtained followed by saline perfusion to remove residual blood and collection of selected tissues for determination of Iodine-125 content by gamma counting.
Results
The peak plasma levels of Iodine-125 galcanezumab and Iodine-125 control immunoglobulin 4 were observed at 72 hours and remained high at 168 hours post-dose. The rank order of tissue levels was dura mater = spleen > trigeminal ganglia ≫hypothalamus = spinal cord = prefrontal cortex = cerebellum. Iodine-125 galcanezumab levels in peripheral tissue (dura mater, spleen, and trigeminal ganglia) averaged 5% to 11% of plasma, whereas all of the central nervous system (CNS) tissue levels and the cerebrospinal fluid levels were < 0.4% of plasma. Distribution of the antibodies into the dura mater and the trigeminal ganglia was similar to that observed in the spleen and significantly greater than exposure in the brain or spinal cord.
Conclusions
The central levels of galcanezumab were relatively low, which would favor the dura mater and trigeminal ganglia as sites of action for its observed clinical efficacy. However, a central site of action cannot be excluded.</description><issn>0333-1024</issn><issn>1468-2982</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kEtLxDAUhYMozvjYu5Is3VTzapouZdBxYEARXYmUNL0dI32MSSrM_HpTRl0Iru6F-53DPQehM0ouKc2yK8I5p4QJmishMkr30JQKqRKWK7aPpuM5Ge8TdOT9OyEklUQeokkUEZ4qNUXDAzi7fgOnG6y7Chvowrh34D77wWO_8QFaXFkfnC2HYPsO9zUOb4Bn88eHyA0jb7e2W0WDYMu-2uAXytLFK17pxugOtkOrS2w73OoGsNPBn6CDWjceTr_nMXq-vXma3SXL-_lidr1MDOdZSFhZE0alrkCBEZWp06okJMsFk1SQFIQGKTJNS57H2JWujTJSSqJLojRjgh-ji53v2vUfA_hQtNYbaJr4VUxXMEZpLpQUPKJkhxrXe--gLtbOttptCkqKsezib9lRcv7tPpQtVL-Cn3YjkOwAr1dQvPeD62La_w2_AOy8h0c</recordid><startdate>201909</startdate><enddate>201909</enddate><creator>Johnson, Kirk W</creator><creator>Morin, S Michelle</creator><creator>Wroblewski, Victor J</creator><creator>Johnson, Michael P</creator><general>SAGE Publications</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201909</creationdate><title>Peripheral and central nervous system distribution of the CGRP neutralizing antibody [125I] galcanezumab in male rats</title><author>Johnson, Kirk W ; Morin, S Michelle ; Wroblewski, Victor J ; Johnson, Michael P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c337t-2bf0216ade8ec4dcf5db00794261405e4ae647a1b39146dafc8c6660ab08a2243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Johnson, Kirk W</creatorcontrib><creatorcontrib>Morin, S Michelle</creatorcontrib><creatorcontrib>Wroblewski, Victor J</creatorcontrib><creatorcontrib>Johnson, Michael P</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cephalalgia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Johnson, Kirk W</au><au>Morin, S Michelle</au><au>Wroblewski, Victor J</au><au>Johnson, Michael P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Peripheral and central nervous system distribution of the CGRP neutralizing antibody [125I] galcanezumab in male rats</atitle><jtitle>Cephalalgia</jtitle><addtitle>Cephalalgia</addtitle><date>2019-09</date><risdate>2019</risdate><volume>39</volume><issue>10</issue><spage>1241</spage><epage>1248</epage><pages>1241-1248</pages><issn>0333-1024</issn><eissn>1468-2982</eissn><abstract>Objective
The objective of this investigation was to examine the distribution of galcanezumab and a control immunoglobulin 4 antibody containing the same constant regions as galcanezumab, into peripheral and central tissues.
Methods
Galcanezumab and a control immunoglobulin 4 antibody were radioiodinated with Iodine-125 to specific activities of 0.11 mCi/mg and 0.16 mCi/mg, respectively. At 24, 72, and 168 hours following subcutaneous injection of either antibody (4 mg/kg), cerebrospinal fluid and plasma were obtained followed by saline perfusion to remove residual blood and collection of selected tissues for determination of Iodine-125 content by gamma counting.
Results
The peak plasma levels of Iodine-125 galcanezumab and Iodine-125 control immunoglobulin 4 were observed at 72 hours and remained high at 168 hours post-dose. The rank order of tissue levels was dura mater = spleen > trigeminal ganglia ≫hypothalamus = spinal cord = prefrontal cortex = cerebellum. Iodine-125 galcanezumab levels in peripheral tissue (dura mater, spleen, and trigeminal ganglia) averaged 5% to 11% of plasma, whereas all of the central nervous system (CNS) tissue levels and the cerebrospinal fluid levels were < 0.4% of plasma. Distribution of the antibodies into the dura mater and the trigeminal ganglia was similar to that observed in the spleen and significantly greater than exposure in the brain or spinal cord.
Conclusions
The central levels of galcanezumab were relatively low, which would favor the dura mater and trigeminal ganglia as sites of action for its observed clinical efficacy. However, a central site of action cannot be excluded.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>31003588</pmid><doi>10.1177/0333102419844711</doi><tpages>8</tpages></addata></record> |
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| source | Sage Journals GOLD Open Access 2024 |
| title | Peripheral and central nervous system distribution of the CGRP neutralizing antibody [125I] galcanezumab in male rats |
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