Decreasing undesirable absorbed radiation to the intestine after administration of radium-223 dichloride for treatment of bone metastases
[ 223 Ra]RaCl 2 is the first alpha-particle emitting radiopharmaceutical to be used for castration-resistant prostate cancer patients with bone metastases because of its excellent therapeutic effects. [ 223 Ra]RaCl 2 is excreted via the intestine into feces, and some is absorbed from the intestine i...
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| Veröffentlicht in: | Scientific reports 2020-07, Vol.10 (1), p.11917, Article 11917 |
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| creator | Ogawa, Kazuma Higashi, Takuma Mishiro, Kenji Wakabayashi, Hiroshi Shiba, Kazuhiro Odani, Akira Kinuya, Seigo |
| description | [
223
Ra]RaCl
2
is the first alpha-particle emitting radiopharmaceutical to be used for castration-resistant prostate cancer patients with bone metastases because of its excellent therapeutic effects. [
223
Ra]RaCl
2
is excreted via the intestine into feces, and some is absorbed from the intestine into the blood, which may be undesirable in terms of the exposure to radiation. Recently, we showed that a complex of
myo
-inositol-hexakisphosphate (InsP6) with zinc is a useful decorporation agent against radiostrontium. In this study, we hypothesized that Zn-InsP6 could bind to not only strontium but also to radium, and could inhibit the absorption of radium from the intestine. In in vitro binding experiments, Zn-InsP6 showed a high binding affinity for radium. In in vivo biodistribution experiments by intravenous injection of [
223
Ra]RaCl
2
after treatment of Zn-InsP6, mice treated with Zn-InsP6 showed significantly lower bone accumulation of radioactivity (34.82 ± 1.83%Dose/g) than the mice in the non-treatment control group (40.30 ± 2.78%Dose/g) at 48 h postinjection. These results indicate that Zn-InsP6 bound radium in the intestine and inhibited the absorption of radium into the blood. Therefore, the insoluble Zn-InsP6 complex has high potential to decrease the side effects of [
223
Ra]RaCl
2
. |
| doi_str_mv | 10.1038/s41598-020-68846-x |
| format | Article |
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223
Ra]RaCl
2
is the first alpha-particle emitting radiopharmaceutical to be used for castration-resistant prostate cancer patients with bone metastases because of its excellent therapeutic effects. [
223
Ra]RaCl
2
is excreted via the intestine into feces, and some is absorbed from the intestine into the blood, which may be undesirable in terms of the exposure to radiation. Recently, we showed that a complex of
myo
-inositol-hexakisphosphate (InsP6) with zinc is a useful decorporation agent against radiostrontium. In this study, we hypothesized that Zn-InsP6 could bind to not only strontium but also to radium, and could inhibit the absorption of radium from the intestine. In in vitro binding experiments, Zn-InsP6 showed a high binding affinity for radium. In in vivo biodistribution experiments by intravenous injection of [
223
Ra]RaCl
2
after treatment of Zn-InsP6, mice treated with Zn-InsP6 showed significantly lower bone accumulation of radioactivity (34.82 ± 1.83%Dose/g) than the mice in the non-treatment control group (40.30 ± 2.78%Dose/g) at 48 h postinjection. These results indicate that Zn-InsP6 bound radium in the intestine and inhibited the absorption of radium into the blood. Therefore, the insoluble Zn-InsP6 complex has high potential to decrease the side effects of [
223
Ra]RaCl
2
.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-68846-x</identifier><identifier>PMID: 32681007</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/308 ; 692/308/153 ; Absorption ; Absorption, Radiation ; Administration, Oral ; Animals ; Blood ; Bone cancer ; Bone Neoplasms - drug therapy ; Bone Neoplasms - secondary ; Castration ; Cations ; Chlorella - metabolism ; Humanities and Social Sciences ; Hydrogen-Ion Concentration ; Inositol ; Intestine ; Intestines - radiation effects ; Intravenous administration ; Male ; Metastases ; Metastasis ; Mice ; multidisciplinary ; Pharmaceuticals ; Phytic Acid - chemistry ; Phytic Acid - metabolism ; Prostate cancer ; Radioactivity ; Radioisotopes ; Radioisotopes - administration & dosage ; Radioisotopes - therapeutic use ; Radium ; Radium - administration & dosage ; Radium - therapeutic use ; Science ; Science (multidisciplinary) ; Strontium ; Tissue Distribution ; Zinc ; Zinc - pharmacology</subject><ispartof>Scientific reports, 2020-07, Vol.10 (1), p.11917, Article 11917</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c623t-eab64954263380c7c146807f50e29a1c6b26362a8cd8f99a67c5e40c4ff4d45a3</citedby><cites>FETCH-LOGICAL-c623t-eab64954263380c7c146807f50e29a1c6b26362a8cd8f99a67c5e40c4ff4d45a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368038/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368038/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32681007$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ogawa, Kazuma</creatorcontrib><creatorcontrib>Higashi, Takuma</creatorcontrib><creatorcontrib>Mishiro, Kenji</creatorcontrib><creatorcontrib>Wakabayashi, Hiroshi</creatorcontrib><creatorcontrib>Shiba, Kazuhiro</creatorcontrib><creatorcontrib>Odani, Akira</creatorcontrib><creatorcontrib>Kinuya, Seigo</creatorcontrib><title>Decreasing undesirable absorbed radiation to the intestine after administration of radium-223 dichloride for treatment of bone metastases</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>[
223
Ra]RaCl
2
is the first alpha-particle emitting radiopharmaceutical to be used for castration-resistant prostate cancer patients with bone metastases because of its excellent therapeutic effects. [
223
Ra]RaCl
2
is excreted via the intestine into feces, and some is absorbed from the intestine into the blood, which may be undesirable in terms of the exposure to radiation. Recently, we showed that a complex of
myo
-inositol-hexakisphosphate (InsP6) with zinc is a useful decorporation agent against radiostrontium. In this study, we hypothesized that Zn-InsP6 could bind to not only strontium but also to radium, and could inhibit the absorption of radium from the intestine. In in vitro binding experiments, Zn-InsP6 showed a high binding affinity for radium. In in vivo biodistribution experiments by intravenous injection of [
223
Ra]RaCl
2
after treatment of Zn-InsP6, mice treated with Zn-InsP6 showed significantly lower bone accumulation of radioactivity (34.82 ± 1.83%Dose/g) than the mice in the non-treatment control group (40.30 ± 2.78%Dose/g) at 48 h postinjection. These results indicate that Zn-InsP6 bound radium in the intestine and inhibited the absorption of radium into the blood. Therefore, the insoluble Zn-InsP6 complex has high potential to decrease the side effects of [
223
Ra]RaCl
2
.</description><subject>692/308</subject><subject>692/308/153</subject><subject>Absorption</subject><subject>Absorption, Radiation</subject><subject>Administration, Oral</subject><subject>Animals</subject><subject>Blood</subject><subject>Bone cancer</subject><subject>Bone Neoplasms - drug therapy</subject><subject>Bone Neoplasms - secondary</subject><subject>Castration</subject><subject>Cations</subject><subject>Chlorella - metabolism</subject><subject>Humanities and Social Sciences</subject><subject>Hydrogen-Ion Concentration</subject><subject>Inositol</subject><subject>Intestine</subject><subject>Intestines - radiation effects</subject><subject>Intravenous administration</subject><subject>Male</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>multidisciplinary</subject><subject>Pharmaceuticals</subject><subject>Phytic Acid - chemistry</subject><subject>Phytic Acid - metabolism</subject><subject>Prostate cancer</subject><subject>Radioactivity</subject><subject>Radioisotopes</subject><subject>Radioisotopes - administration & dosage</subject><subject>Radioisotopes - therapeutic use</subject><subject>Radium</subject><subject>Radium - administration & dosage</subject><subject>Radium - therapeutic use</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Strontium</subject><subject>Tissue Distribution</subject><subject>Zinc</subject><subject>Zinc - pharmacology</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kd1KHTEUhUNpqWJ9gV6UgNej-ZtM5qZQtP6A0Jv2OmSSnXMiZxKbZMQ-Qt-60bFWbxoC2bC_vdYmC6GPlBxTwtVJEbQfVUcY6aRSQnb3b9A-I6LvGGfs7Yt6Dx2WckPa6dko6Pge7XEmFSVk2Ee_z8BmMCXEDV6igxKymXaAzVRSnsDhbFwwNaSIa8J1CzjECqWG2BhfIWPj5hBDqXmlkn8cWeaOMY5dsNtdysEB9inj2qzqDLE-YFNqGjNUU9qF8gG982ZX4PDpPUA_zr9-P73srr9dXJ1-ue6sZLx2YCYpxl4wybkidrBUSEUG3xNgo6FWTq0jmVHWKT-ORg62B0Gs8F440Rt-gD6vurfLNIOzbZtsdvo2h9nkXzqZoF93YtjqTbrTA29GXDWBoyeBnH4u7S_0TVpybDtrJpjopRzp0Ci2UjanUjL4ZwdK9EOCek1QtwT1Y4L6vg19ernb88jfvBrAV6C0VtxA_uf9H9k__pmqqg</recordid><startdate>20200717</startdate><enddate>20200717</enddate><creator>Ogawa, Kazuma</creator><creator>Higashi, Takuma</creator><creator>Mishiro, Kenji</creator><creator>Wakabayashi, Hiroshi</creator><creator>Shiba, Kazuhiro</creator><creator>Odani, Akira</creator><creator>Kinuya, Seigo</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20200717</creationdate><title>Decreasing undesirable absorbed radiation to the intestine after administration of radium-223 dichloride for treatment of bone metastases</title><author>Ogawa, Kazuma ; Higashi, Takuma ; Mishiro, Kenji ; Wakabayashi, Hiroshi ; Shiba, Kazuhiro ; Odani, Akira ; Kinuya, Seigo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c623t-eab64954263380c7c146807f50e29a1c6b26362a8cd8f99a67c5e40c4ff4d45a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>692/308</topic><topic>692/308/153</topic><topic>Absorption</topic><topic>Absorption, Radiation</topic><topic>Administration, Oral</topic><topic>Animals</topic><topic>Blood</topic><topic>Bone cancer</topic><topic>Bone Neoplasms - drug therapy</topic><topic>Bone Neoplasms - secondary</topic><topic>Castration</topic><topic>Cations</topic><topic>Chlorella - metabolism</topic><topic>Humanities and Social Sciences</topic><topic>Hydrogen-Ion Concentration</topic><topic>Inositol</topic><topic>Intestine</topic><topic>Intestines - radiation effects</topic><topic>Intravenous administration</topic><topic>Male</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>multidisciplinary</topic><topic>Pharmaceuticals</topic><topic>Phytic Acid - chemistry</topic><topic>Phytic Acid - metabolism</topic><topic>Prostate cancer</topic><topic>Radioactivity</topic><topic>Radioisotopes</topic><topic>Radioisotopes - administration & dosage</topic><topic>Radioisotopes - therapeutic use</topic><topic>Radium</topic><topic>Radium - administration & dosage</topic><topic>Radium - therapeutic use</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Strontium</topic><topic>Tissue Distribution</topic><topic>Zinc</topic><topic>Zinc - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ogawa, Kazuma</creatorcontrib><creatorcontrib>Higashi, Takuma</creatorcontrib><creatorcontrib>Mishiro, Kenji</creatorcontrib><creatorcontrib>Wakabayashi, Hiroshi</creatorcontrib><creatorcontrib>Shiba, Kazuhiro</creatorcontrib><creatorcontrib>Odani, Akira</creatorcontrib><creatorcontrib>Kinuya, Seigo</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ogawa, Kazuma</au><au>Higashi, Takuma</au><au>Mishiro, Kenji</au><au>Wakabayashi, Hiroshi</au><au>Shiba, Kazuhiro</au><au>Odani, Akira</au><au>Kinuya, Seigo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreasing undesirable absorbed radiation to the intestine after administration of radium-223 dichloride for treatment of bone metastases</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-07-17</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>11917</spage><pages>11917-</pages><artnum>11917</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>[
223
Ra]RaCl
2
is the first alpha-particle emitting radiopharmaceutical to be used for castration-resistant prostate cancer patients with bone metastases because of its excellent therapeutic effects. [
223
Ra]RaCl
2
is excreted via the intestine into feces, and some is absorbed from the intestine into the blood, which may be undesirable in terms of the exposure to radiation. Recently, we showed that a complex of
myo
-inositol-hexakisphosphate (InsP6) with zinc is a useful decorporation agent against radiostrontium. In this study, we hypothesized that Zn-InsP6 could bind to not only strontium but also to radium, and could inhibit the absorption of radium from the intestine. In in vitro binding experiments, Zn-InsP6 showed a high binding affinity for radium. In in vivo biodistribution experiments by intravenous injection of [
223
Ra]RaCl
2
after treatment of Zn-InsP6, mice treated with Zn-InsP6 showed significantly lower bone accumulation of radioactivity (34.82 ± 1.83%Dose/g) than the mice in the non-treatment control group (40.30 ± 2.78%Dose/g) at 48 h postinjection. These results indicate that Zn-InsP6 bound radium in the intestine and inhibited the absorption of radium into the blood. Therefore, the insoluble Zn-InsP6 complex has high potential to decrease the side effects of [
223
Ra]RaCl
2
.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32681007</pmid><doi>10.1038/s41598-020-68846-x</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | Scientific reports, 2020-07, Vol.10 (1), p.11917, Article 11917 |
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| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 692/308 692/308/153 Absorption Absorption, Radiation Administration, Oral Animals Blood Bone cancer Bone Neoplasms - drug therapy Bone Neoplasms - secondary Castration Cations Chlorella - metabolism Humanities and Social Sciences Hydrogen-Ion Concentration Inositol Intestine Intestines - radiation effects Intravenous administration Male Metastases Metastasis Mice multidisciplinary Pharmaceuticals Phytic Acid - chemistry Phytic Acid - metabolism Prostate cancer Radioactivity Radioisotopes Radioisotopes - administration & dosage Radioisotopes - therapeutic use Radium Radium - administration & dosage Radium - therapeutic use Science Science (multidisciplinary) Strontium Tissue Distribution Zinc Zinc - pharmacology |
| title | Decreasing undesirable absorbed radiation to the intestine after administration of radium-223 dichloride for treatment of bone metastases |
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