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Imaging doxorubicin and polymer-drug conjugates of doxorubicin-induced cardiotoxicity with bispecific anti-myosin-anti-DTPA antibody and Tc-99m-labeled polymers
Radiolabeled anti-myosin imaging is well-established for imaging doxorubicin-induced cardiotoxicity. However, to enable imaging of drug-induced cardiotoxicity in small experimental animals, pretargeting with bispecific anti-myosin-anti-DTPA-Fab-Fab’ and targeting with high-specific radioactivity Tc-...
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| Published in: | Journal of nuclear cardiology 2019-08, Vol.26 (4), p.1327-1344 |
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| container_end_page | 1344 |
| container_issue | 4 |
| container_start_page | 1327 |
| container_title | Journal of nuclear cardiology |
| container_volume | 26 |
| creator | Panwar, Rajiv Bhattarai, Prashant Patil, Vishwesh Gada, Keyur Majewski, Stan Khaw, Ban An |
| description | Radiolabeled anti-myosin imaging is well-established for imaging doxorubicin-induced cardiotoxicity. However, to enable imaging of drug-induced cardiotoxicity in small experimental animals, pretargeting with bispecific anti-myosin-anti-DTPA-Fab-Fab’ and targeting with high-specific radioactivity Tc-99m-DTPA-succinylated-polylysine (DSPL) was developed.
Mice were injected biweekly with 10 mg/kg Dox or its equivalent as D-Dox-PGA. Tc-99m-DSPL myocardial activity after pretargeting with bsAb-Fab-Fab’ was determined after gamma imaging performed at day 7 for Dox-treated mice and day 39 for all others.
Mice treated with 10 mg/kg Dox lost 10% total body weight in 1 week and 20% after a second dose. Pretargeted mice treated with 30 mg/kg cumulative D-Dox-PGA dose showed no loss of body weight for the duration of the study. Cardiotoxicity was confirmed by gamma imaging and scintillation counting (1.9 ± 0.25 [mean% ID/g ± SD]) after 1 dose of Dox. Mice injected with 3 × 10 mg/kg Dox equivalent as D-Dox-PGA (0.4 ± 0.04, P < .01) and untreated 2 control groups (0.20 ± 0.05 and 0.19 ± 0.04, P < .01) showed significantly lower myocardial anti-myosin radioactivity relative to the 10 mg/kg Dox group.
Pretargeting with bsAb-Fab-Fab’ and targeting with Tc-99m labeled high-specific activity polymers enabled early visualization of doxorubicin induce cardiotoxicity in mice. Tolerated dose of D-Dox-PGA was greater than to 30 mg/kg Dox-equivalent dose with minimal cardiotoxicity. |
| doi_str_mv | 10.1007/s12350-018-1190-2 |
| format | article |
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Mice were injected biweekly with 10 mg/kg Dox or its equivalent as D-Dox-PGA. Tc-99m-DSPL myocardial activity after pretargeting with bsAb-Fab-Fab’ was determined after gamma imaging performed at day 7 for Dox-treated mice and day 39 for all others.
Mice treated with 10 mg/kg Dox lost 10% total body weight in 1 week and 20% after a second dose. Pretargeted mice treated with 30 mg/kg cumulative D-Dox-PGA dose showed no loss of body weight for the duration of the study. Cardiotoxicity was confirmed by gamma imaging and scintillation counting (1.9 ± 0.25 [mean% ID/g ± SD]) after 1 dose of Dox. Mice injected with 3 × 10 mg/kg Dox equivalent as D-Dox-PGA (0.4 ± 0.04, P < .01) and untreated 2 control groups (0.20 ± 0.05 and 0.19 ± 0.04, P < .01) showed significantly lower myocardial anti-myosin radioactivity relative to the 10 mg/kg Dox group.
Pretargeting with bsAb-Fab-Fab’ and targeting with Tc-99m labeled high-specific activity polymers enabled early visualization of doxorubicin induce cardiotoxicity in mice. Tolerated dose of D-Dox-PGA was greater than to 30 mg/kg Dox-equivalent dose with minimal cardiotoxicity.</description><identifier>ISSN: 1071-3581</identifier><identifier>ISSN: 1532-6551</identifier><identifier>EISSN: 1532-6551</identifier><identifier>DOI: 10.1007/s12350-018-1190-2</identifier><identifier>PMID: 29392624</identifier><language>eng</language><publisher>Cham: Elsevier Inc</publisher><subject>Animals ; Antibiotics, Antineoplastic - adverse effects ; ANTIBODIES ; Antibodies, Bispecific ; Cardiology ; Cardiotoxicity - diagnostic imaging ; Cardiotoxicity - etiology ; Disease Models, Animal ; DOXORUBICIN ; Doxorubicin - adverse effects ; Doxorubicin cardiotoxicity ; Drug dosages ; DTPA ; gamma imaging ; Imaging ; Male ; Medicine ; Medicine & Public Health ; MICE ; Mice, Inbred BALB C ; MYOSIN ; Nuclear Medicine ; Original Article ; Pentetic Acid ; polymer-drug conjugates ; POLYMERS ; pretargeting with bispecific antibody ; RADIOACTIVITY ; Radiology ; RADIOLOGY AND NUCLEAR MEDICINE ; SCINTILLATION COUNTING ; Technetium ; TECHNETIUM 99 ; Tomography, Emission-Computed, Single-Photon</subject><ispartof>Journal of nuclear cardiology, 2019-08, Vol.26 (4), p.1327-1344</ispartof><rights>2019 American Society of Nuclear Cardiology. Published by ELSEVIER INC. All rights reserved.</rights><rights>American Society of Nuclear Cardiology 2018</rights><rights>Journal of Nuclear Cardiology is a copyright of Springer, (2018). All Rights Reserved.</rights><rights>Copyright Springer Nature B.V. 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c480t-17e4345035393f19a2c5dd45fac576ebd7dc89b41d978dc905aa73f127840fa43</citedby><cites>FETCH-LOGICAL-c480t-17e4345035393f19a2c5dd45fac576ebd7dc89b41d978dc905aa73f127840fa43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29392624$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22962012$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Panwar, Rajiv</creatorcontrib><creatorcontrib>Bhattarai, Prashant</creatorcontrib><creatorcontrib>Patil, Vishwesh</creatorcontrib><creatorcontrib>Gada, Keyur</creatorcontrib><creatorcontrib>Majewski, Stan</creatorcontrib><creatorcontrib>Khaw, Ban An</creatorcontrib><title>Imaging doxorubicin and polymer-drug conjugates of doxorubicin-induced cardiotoxicity with bispecific anti-myosin-anti-DTPA antibody and Tc-99m-labeled polymers</title><title>Journal of nuclear cardiology</title><addtitle>J. Nucl. Cardiol</addtitle><addtitle>J Nucl Cardiol</addtitle><description>Radiolabeled anti-myosin imaging is well-established for imaging doxorubicin-induced cardiotoxicity. However, to enable imaging of drug-induced cardiotoxicity in small experimental animals, pretargeting with bispecific anti-myosin-anti-DTPA-Fab-Fab’ and targeting with high-specific radioactivity Tc-99m-DTPA-succinylated-polylysine (DSPL) was developed.
Mice were injected biweekly with 10 mg/kg Dox or its equivalent as D-Dox-PGA. Tc-99m-DSPL myocardial activity after pretargeting with bsAb-Fab-Fab’ was determined after gamma imaging performed at day 7 for Dox-treated mice and day 39 for all others.
Mice treated with 10 mg/kg Dox lost 10% total body weight in 1 week and 20% after a second dose. Pretargeted mice treated with 30 mg/kg cumulative D-Dox-PGA dose showed no loss of body weight for the duration of the study. Cardiotoxicity was confirmed by gamma imaging and scintillation counting (1.9 ± 0.25 [mean% ID/g ± SD]) after 1 dose of Dox. Mice injected with 3 × 10 mg/kg Dox equivalent as D-Dox-PGA (0.4 ± 0.04, P < .01) and untreated 2 control groups (0.20 ± 0.05 and 0.19 ± 0.04, P < .01) showed significantly lower myocardial anti-myosin radioactivity relative to the 10 mg/kg Dox group.
Pretargeting with bsAb-Fab-Fab’ and targeting with Tc-99m labeled high-specific activity polymers enabled early visualization of doxorubicin induce cardiotoxicity in mice. Tolerated dose of D-Dox-PGA was greater than to 30 mg/kg Dox-equivalent dose with minimal cardiotoxicity.</description><subject>Animals</subject><subject>Antibiotics, Antineoplastic - adverse effects</subject><subject>ANTIBODIES</subject><subject>Antibodies, Bispecific</subject><subject>Cardiology</subject><subject>Cardiotoxicity - diagnostic imaging</subject><subject>Cardiotoxicity - etiology</subject><subject>Disease Models, Animal</subject><subject>DOXORUBICIN</subject><subject>Doxorubicin - adverse effects</subject><subject>Doxorubicin cardiotoxicity</subject><subject>Drug dosages</subject><subject>DTPA</subject><subject>gamma imaging</subject><subject>Imaging</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>MICE</subject><subject>Mice, Inbred BALB C</subject><subject>MYOSIN</subject><subject>Nuclear Medicine</subject><subject>Original Article</subject><subject>Pentetic Acid</subject><subject>polymer-drug conjugates</subject><subject>POLYMERS</subject><subject>pretargeting with bispecific antibody</subject><subject>RADIOACTIVITY</subject><subject>Radiology</subject><subject>RADIOLOGY AND NUCLEAR MEDICINE</subject><subject>SCINTILLATION COUNTING</subject><subject>Technetium</subject><subject>TECHNETIUM 99</subject><subject>Tomography, Emission-Computed, Single-Photon</subject><issn>1071-3581</issn><issn>1532-6551</issn><issn>1532-6551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kc9u1DAQxqOKqi2FB-CCInE2-H9icaoKhUqVymE5W47tpF5t4sVOSvM2PGpnN2XV055mNP59M575iuIDwZ8JxtWXTCgTGGFSI0IURvSkuCCCUSSFIG8gxxVBTNTkvHib8xpjrJhSZ8U5hUgl5RfFv9vedGHoShefYpqaYMNQmsGV27iZe5-QS1NX2jisp86MPpexfY2iMLjJeldak1yIY3yC6jiXf8P4UDYhb70NbbDQcQyon2MGyT7_tvp1ta820c37gSuLlOrRxjR-4w_z87vitDWb7N-_xMvi98331fVPdHf_4_b66g5ZXuMRkcpzxgVmginWEmWoFc5x0RorKukbVzlbq4YTp6raWYWFMRWAtKo5bg1nl8WnpW_MY9AZtvD2AfYevB01pUpSDNc-UNsU_0w-j3odpzTAx4CRXNKKSnmMIkoxyZjgDCiyUDbFnJNv9TaF3qRZE6x3_urFXw3-6p2_ejf_40vnqem9Oyj-GwoAXYAMT0Pn06vRR7p-XUQeDvwYQAT7-wF8DWm3vovhiPoZX1TEvA</recordid><startdate>20190801</startdate><enddate>20190801</enddate><creator>Panwar, Rajiv</creator><creator>Bhattarai, Prashant</creator><creator>Patil, Vishwesh</creator><creator>Gada, Keyur</creator><creator>Majewski, Stan</creator><creator>Khaw, Ban An</creator><general>Elsevier Inc</general><general>Springer International Publishing</general><general>Springer Nature B.V</general><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>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>OTOTI</scope></search><sort><creationdate>20190801</creationdate><title>Imaging doxorubicin and polymer-drug conjugates of doxorubicin-induced cardiotoxicity with bispecific anti-myosin-anti-DTPA antibody and Tc-99m-labeled polymers</title><author>Panwar, Rajiv ; 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Nucl. Cardiol</stitle><addtitle>J Nucl Cardiol</addtitle><date>2019-08-01</date><risdate>2019</risdate><volume>26</volume><issue>4</issue><spage>1327</spage><epage>1344</epage><pages>1327-1344</pages><issn>1071-3581</issn><issn>1532-6551</issn><eissn>1532-6551</eissn><abstract>Radiolabeled anti-myosin imaging is well-established for imaging doxorubicin-induced cardiotoxicity. However, to enable imaging of drug-induced cardiotoxicity in small experimental animals, pretargeting with bispecific anti-myosin-anti-DTPA-Fab-Fab’ and targeting with high-specific radioactivity Tc-99m-DTPA-succinylated-polylysine (DSPL) was developed.
Mice were injected biweekly with 10 mg/kg Dox or its equivalent as D-Dox-PGA. Tc-99m-DSPL myocardial activity after pretargeting with bsAb-Fab-Fab’ was determined after gamma imaging performed at day 7 for Dox-treated mice and day 39 for all others.
Mice treated with 10 mg/kg Dox lost 10% total body weight in 1 week and 20% after a second dose. Pretargeted mice treated with 30 mg/kg cumulative D-Dox-PGA dose showed no loss of body weight for the duration of the study. Cardiotoxicity was confirmed by gamma imaging and scintillation counting (1.9 ± 0.25 [mean% ID/g ± SD]) after 1 dose of Dox. Mice injected with 3 × 10 mg/kg Dox equivalent as D-Dox-PGA (0.4 ± 0.04, P < .01) and untreated 2 control groups (0.20 ± 0.05 and 0.19 ± 0.04, P < .01) showed significantly lower myocardial anti-myosin radioactivity relative to the 10 mg/kg Dox group.
Pretargeting with bsAb-Fab-Fab’ and targeting with Tc-99m labeled high-specific activity polymers enabled early visualization of doxorubicin induce cardiotoxicity in mice. Tolerated dose of D-Dox-PGA was greater than to 30 mg/kg Dox-equivalent dose with minimal cardiotoxicity.</abstract><cop>Cham</cop><pub>Elsevier Inc</pub><pmid>29392624</pmid><doi>10.1007/s12350-018-1190-2</doi><tpages>18</tpages></addata></record> |
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| identifier | ISSN: 1071-3581 |
| ispartof | Journal of nuclear cardiology, 2019-08, Vol.26 (4), p.1327-1344 |
| issn | 1071-3581 1532-6551 1532-6551 |
| language | eng |
| recordid | cdi_osti_scitechconnect_22962012 |
| source | Springer Link |
| subjects | Animals Antibiotics, Antineoplastic - adverse effects ANTIBODIES Antibodies, Bispecific Cardiology Cardiotoxicity - diagnostic imaging Cardiotoxicity - etiology Disease Models, Animal DOXORUBICIN Doxorubicin - adverse effects Doxorubicin cardiotoxicity Drug dosages DTPA gamma imaging Imaging Male Medicine Medicine & Public Health MICE Mice, Inbred BALB C MYOSIN Nuclear Medicine Original Article Pentetic Acid polymer-drug conjugates POLYMERS pretargeting with bispecific antibody RADIOACTIVITY Radiology RADIOLOGY AND NUCLEAR MEDICINE SCINTILLATION COUNTING Technetium TECHNETIUM 99 Tomography, Emission-Computed, Single-Photon |
| title | Imaging doxorubicin and polymer-drug conjugates of doxorubicin-induced cardiotoxicity with bispecific anti-myosin-anti-DTPA antibody and Tc-99m-labeled polymers |
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