Imaging of Chemotherapy-Induced Acute Cardiotoxicity with 18 F-Labeled Lipophilic Cations
Many chemotherapy agents are toxic to the heart, such that increasing numbers of cancer survivors are now living with the potentially lethal cardiovascular consequences of their treatment. Earlier and more sensitive detection of chemotherapy-induced cardiotoxicity may allow improved treatment strate...
Gespeichert in:
| Veröffentlicht in: | Journal of Nuclear Medicine 2019-12, Vol.60 (12), p.1750-1756 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1756 |
|---|---|
| container_issue | 12 |
| container_start_page | 1750 |
| container_title | Journal of Nuclear Medicine |
| container_volume | 60 |
| creator | McCluskey, Stuart P Haslop, Anna Coello, Christopher Gunn, Roger N Tate, Edward W Southworth, Richard Plisson, Christophe Long, Nicholas J Wells, Lisa A |
| description | Many chemotherapy agents are toxic to the heart, such that increasing numbers of cancer survivors are now living with the potentially lethal cardiovascular consequences of their treatment. Earlier and more sensitive detection of chemotherapy-induced cardiotoxicity may allow improved treatment strategies and increase long-term survival. Lipophilic cation PET tracers may be suitable for early detection of cardiotoxicity. This study aimed to evaluate an
F-labeled lipophilic phosphonium cation, [1-(2-
F-fluoroethyl),1
[1,2,3]triazole-4-ethylene]triphenylphosphonium bromide (
F-MitoPhos), as a cardiac imaging agent, comparing it with leading PET and SPECT lipophilic cationic tracers before further assessing its potential for imaging cardiotoxicity in an acute doxorubicin model.
Cardiac uptake and response to decreased mitochondrial membrane potential of
F-MitoPhos and
Tc-sestamibi were tested in isolated perfused rat hearts. Baseline pharmacokinetic profiles of
F-MitoPhos and
F-fluorobenzyltriphenylphosphonium and their response to acute doxorubicin-induced cardiotoxicity were assessed in rats in vivo (10, 15, or 20 mg of doxorubicin per kilogram, intravenously, 48 h beforehand).
Cardiac retention of
F-MitoPhos was more than double that of
Tc-sestamibi in isolated perfused rat hearts. A favorable biodistribution of
F-MitoPhos in vivo was observed, with heart-to-tissue ratios of 304 ± 186, 11.2 ± 1.2, and 3.8 ± 0.6 for plasma, liver, and lung, respectively (60 min). A significant dose-dependent loss of cardiac retention of
F-MitoPhos was observed on doxorubicin treatment, with average cardiac SUV from 30 to 60 min (mean ± SD) decreasing from 3.5 ± 0.5 (control) to 1.8 ± 0.1 (doxorubicin, 20 mg/kg). Other assessed biomarkers showed no alterations.
F-MitoPhos showed pharmacokinetic parameters suitable for cardiac imaging. A significant dose response of cardiac uptake to doxorubicin treatment was observed before detectable biomarker alterations.
F-MitoPhos is therefore a promising tracer for imaging chemotherapy-induced cardiotoxicity. To our knowledge, this is the first demonstration of radiolabeled lipophilic cations being used for the PET imaging of chemotherapy-induced cardiotoxicity and indicates the potential application of these compounds in this area. |
| doi_str_mv | 10.2967/jnumed.119.226787 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_2967_jnumed_119_226787</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>31147403</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1133-65d69a731c3c29801926a0836e2d145bb57a4f1bd11fd2113c8d5610ab772bbd3</originalsourceid><addsrcrecordid>eNo1kLlOw0AYhFcIRELgAWjQvoDD_rvew2VkkRDJEg0UVNZejjeKD_kQ5O1xZFJNMfNN8SH0DGRNEyFfj_VYebcGSNaUCqnkDVoCZzziQshbtCQgIOKc8AV66PsjIUQope7RggHEMiZsib73lT6E-oCbAqelr5qh9J1uz9G-dqP1Dm_sOHic6s6FZmh-gw3DGf-EocSg8DbKtPGnaZaFtmnLcAp22g6hqftHdFfoU--f_nOFvrZvn-l7lH3s9ukmiywAY5HgTiRaMrDM0kQRSKjQRDHhqYOYG8OljgswDqBwdEKsclwA0UZKaoxjKwTzr-2avu98kbddqHR3zoHkF035rCmfNOWzpol5mZl2NJfqSly9sD8PAmRM</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Imaging of Chemotherapy-Induced Acute Cardiotoxicity with 18 F-Labeled Lipophilic Cations</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>McCluskey, Stuart P ; Haslop, Anna ; Coello, Christopher ; Gunn, Roger N ; Tate, Edward W ; Southworth, Richard ; Plisson, Christophe ; Long, Nicholas J ; Wells, Lisa A</creator><creatorcontrib>McCluskey, Stuart P ; Haslop, Anna ; Coello, Christopher ; Gunn, Roger N ; Tate, Edward W ; Southworth, Richard ; Plisson, Christophe ; Long, Nicholas J ; Wells, Lisa A</creatorcontrib><description>Many chemotherapy agents are toxic to the heart, such that increasing numbers of cancer survivors are now living with the potentially lethal cardiovascular consequences of their treatment. Earlier and more sensitive detection of chemotherapy-induced cardiotoxicity may allow improved treatment strategies and increase long-term survival. Lipophilic cation PET tracers may be suitable for early detection of cardiotoxicity. This study aimed to evaluate an
F-labeled lipophilic phosphonium cation, [1-(2-
F-fluoroethyl),1
[1,2,3]triazole-4-ethylene]triphenylphosphonium bromide (
F-MitoPhos), as a cardiac imaging agent, comparing it with leading PET and SPECT lipophilic cationic tracers before further assessing its potential for imaging cardiotoxicity in an acute doxorubicin model.
Cardiac uptake and response to decreased mitochondrial membrane potential of
F-MitoPhos and
Tc-sestamibi were tested in isolated perfused rat hearts. Baseline pharmacokinetic profiles of
F-MitoPhos and
F-fluorobenzyltriphenylphosphonium and their response to acute doxorubicin-induced cardiotoxicity were assessed in rats in vivo (10, 15, or 20 mg of doxorubicin per kilogram, intravenously, 48 h beforehand).
Cardiac retention of
F-MitoPhos was more than double that of
Tc-sestamibi in isolated perfused rat hearts. A favorable biodistribution of
F-MitoPhos in vivo was observed, with heart-to-tissue ratios of 304 ± 186, 11.2 ± 1.2, and 3.8 ± 0.6 for plasma, liver, and lung, respectively (60 min). A significant dose-dependent loss of cardiac retention of
F-MitoPhos was observed on doxorubicin treatment, with average cardiac SUV from 30 to 60 min (mean ± SD) decreasing from 3.5 ± 0.5 (control) to 1.8 ± 0.1 (doxorubicin, 20 mg/kg). Other assessed biomarkers showed no alterations.
F-MitoPhos showed pharmacokinetic parameters suitable for cardiac imaging. A significant dose response of cardiac uptake to doxorubicin treatment was observed before detectable biomarker alterations.
F-MitoPhos is therefore a promising tracer for imaging chemotherapy-induced cardiotoxicity. To our knowledge, this is the first demonstration of radiolabeled lipophilic cations being used for the PET imaging of chemotherapy-induced cardiotoxicity and indicates the potential application of these compounds in this area.</description><identifier>ISSN: 0161-5505</identifier><identifier>EISSN: 1535-5667</identifier><identifier>EISSN: 2159-662X</identifier><identifier>DOI: 10.2967/jnumed.119.226787</identifier><identifier>PMID: 31147403</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Antineoplastic Agents - adverse effects ; Cardiotoxicity - diagnostic imaging ; Cardiotoxicity - etiology ; Cardiotoxicity - metabolism ; Doxorubicin - adverse effects ; Fluorine Radioisotopes ; Hydrophobic and Hydrophilic Interactions ; Isotope Labeling ; Male ; Organophosphorus Compounds - chemistry ; Organophosphorus Compounds - pharmacokinetics ; Positron-Emission Tomography ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution</subject><ispartof>Journal of Nuclear Medicine, 2019-12, Vol.60 (12), p.1750-1756</ispartof><rights>2019 by the Society of Nuclear Medicine and Molecular Imaging.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1133-65d69a731c3c29801926a0836e2d145bb57a4f1bd11fd2113c8d5610ab772bbd3</citedby><cites>FETCH-LOGICAL-c1133-65d69a731c3c29801926a0836e2d145bb57a4f1bd11fd2113c8d5610ab772bbd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31147403$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McCluskey, Stuart P</creatorcontrib><creatorcontrib>Haslop, Anna</creatorcontrib><creatorcontrib>Coello, Christopher</creatorcontrib><creatorcontrib>Gunn, Roger N</creatorcontrib><creatorcontrib>Tate, Edward W</creatorcontrib><creatorcontrib>Southworth, Richard</creatorcontrib><creatorcontrib>Plisson, Christophe</creatorcontrib><creatorcontrib>Long, Nicholas J</creatorcontrib><creatorcontrib>Wells, Lisa A</creatorcontrib><title>Imaging of Chemotherapy-Induced Acute Cardiotoxicity with 18 F-Labeled Lipophilic Cations</title><title>Journal of Nuclear Medicine</title><addtitle>J Nucl Med</addtitle><description>Many chemotherapy agents are toxic to the heart, such that increasing numbers of cancer survivors are now living with the potentially lethal cardiovascular consequences of their treatment. Earlier and more sensitive detection of chemotherapy-induced cardiotoxicity may allow improved treatment strategies and increase long-term survival. Lipophilic cation PET tracers may be suitable for early detection of cardiotoxicity. This study aimed to evaluate an
F-labeled lipophilic phosphonium cation, [1-(2-
F-fluoroethyl),1
[1,2,3]triazole-4-ethylene]triphenylphosphonium bromide (
F-MitoPhos), as a cardiac imaging agent, comparing it with leading PET and SPECT lipophilic cationic tracers before further assessing its potential for imaging cardiotoxicity in an acute doxorubicin model.
Cardiac uptake and response to decreased mitochondrial membrane potential of
F-MitoPhos and
Tc-sestamibi were tested in isolated perfused rat hearts. Baseline pharmacokinetic profiles of
F-MitoPhos and
F-fluorobenzyltriphenylphosphonium and their response to acute doxorubicin-induced cardiotoxicity were assessed in rats in vivo (10, 15, or 20 mg of doxorubicin per kilogram, intravenously, 48 h beforehand).
Cardiac retention of
F-MitoPhos was more than double that of
Tc-sestamibi in isolated perfused rat hearts. A favorable biodistribution of
F-MitoPhos in vivo was observed, with heart-to-tissue ratios of 304 ± 186, 11.2 ± 1.2, and 3.8 ± 0.6 for plasma, liver, and lung, respectively (60 min). A significant dose-dependent loss of cardiac retention of
F-MitoPhos was observed on doxorubicin treatment, with average cardiac SUV from 30 to 60 min (mean ± SD) decreasing from 3.5 ± 0.5 (control) to 1.8 ± 0.1 (doxorubicin, 20 mg/kg). Other assessed biomarkers showed no alterations.
F-MitoPhos showed pharmacokinetic parameters suitable for cardiac imaging. A significant dose response of cardiac uptake to doxorubicin treatment was observed before detectable biomarker alterations.
F-MitoPhos is therefore a promising tracer for imaging chemotherapy-induced cardiotoxicity. To our knowledge, this is the first demonstration of radiolabeled lipophilic cations being used for the PET imaging of chemotherapy-induced cardiotoxicity and indicates the potential application of these compounds in this area.</description><subject>Animals</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Cardiotoxicity - diagnostic imaging</subject><subject>Cardiotoxicity - etiology</subject><subject>Cardiotoxicity - metabolism</subject><subject>Doxorubicin - adverse effects</subject><subject>Fluorine Radioisotopes</subject><subject>Hydrophobic and Hydrophilic Interactions</subject><subject>Isotope Labeling</subject><subject>Male</subject><subject>Organophosphorus Compounds - chemistry</subject><subject>Organophosphorus Compounds - pharmacokinetics</subject><subject>Positron-Emission Tomography</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Tissue Distribution</subject><issn>0161-5505</issn><issn>1535-5667</issn><issn>2159-662X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kLlOw0AYhFcIRELgAWjQvoDD_rvew2VkkRDJEg0UVNZejjeKD_kQ5O1xZFJNMfNN8SH0DGRNEyFfj_VYebcGSNaUCqnkDVoCZzziQshbtCQgIOKc8AV66PsjIUQope7RggHEMiZsib73lT6E-oCbAqelr5qh9J1uz9G-dqP1Dm_sOHic6s6FZmh-gw3DGf-EocSg8DbKtPGnaZaFtmnLcAp22g6hqftHdFfoU--f_nOFvrZvn-l7lH3s9ukmiywAY5HgTiRaMrDM0kQRSKjQRDHhqYOYG8OljgswDqBwdEKsclwA0UZKaoxjKwTzr-2avu98kbddqHR3zoHkF035rCmfNOWzpol5mZl2NJfqSly9sD8PAmRM</recordid><startdate>201912</startdate><enddate>201912</enddate><creator>McCluskey, Stuart P</creator><creator>Haslop, Anna</creator><creator>Coello, Christopher</creator><creator>Gunn, Roger N</creator><creator>Tate, Edward W</creator><creator>Southworth, Richard</creator><creator>Plisson, Christophe</creator><creator>Long, Nicholas J</creator><creator>Wells, Lisa A</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201912</creationdate><title>Imaging of Chemotherapy-Induced Acute Cardiotoxicity with 18 F-Labeled Lipophilic Cations</title><author>McCluskey, Stuart P ; Haslop, Anna ; Coello, Christopher ; Gunn, Roger N ; Tate, Edward W ; Southworth, Richard ; Plisson, Christophe ; Long, Nicholas J ; Wells, Lisa A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1133-65d69a731c3c29801926a0836e2d145bb57a4f1bd11fd2113c8d5610ab772bbd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Cardiotoxicity - diagnostic imaging</topic><topic>Cardiotoxicity - etiology</topic><topic>Cardiotoxicity - metabolism</topic><topic>Doxorubicin - adverse effects</topic><topic>Fluorine Radioisotopes</topic><topic>Hydrophobic and Hydrophilic Interactions</topic><topic>Isotope Labeling</topic><topic>Male</topic><topic>Organophosphorus Compounds - chemistry</topic><topic>Organophosphorus Compounds - pharmacokinetics</topic><topic>Positron-Emission Tomography</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McCluskey, Stuart P</creatorcontrib><creatorcontrib>Haslop, Anna</creatorcontrib><creatorcontrib>Coello, Christopher</creatorcontrib><creatorcontrib>Gunn, Roger N</creatorcontrib><creatorcontrib>Tate, Edward W</creatorcontrib><creatorcontrib>Southworth, Richard</creatorcontrib><creatorcontrib>Plisson, Christophe</creatorcontrib><creatorcontrib>Long, Nicholas J</creatorcontrib><creatorcontrib>Wells, Lisa A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of Nuclear Medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McCluskey, Stuart P</au><au>Haslop, Anna</au><au>Coello, Christopher</au><au>Gunn, Roger N</au><au>Tate, Edward W</au><au>Southworth, Richard</au><au>Plisson, Christophe</au><au>Long, Nicholas J</au><au>Wells, Lisa A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Imaging of Chemotherapy-Induced Acute Cardiotoxicity with 18 F-Labeled Lipophilic Cations</atitle><jtitle>Journal of Nuclear Medicine</jtitle><addtitle>J Nucl Med</addtitle><date>2019-12</date><risdate>2019</risdate><volume>60</volume><issue>12</issue><spage>1750</spage><epage>1756</epage><pages>1750-1756</pages><issn>0161-5505</issn><eissn>1535-5667</eissn><eissn>2159-662X</eissn><abstract>Many chemotherapy agents are toxic to the heart, such that increasing numbers of cancer survivors are now living with the potentially lethal cardiovascular consequences of their treatment. Earlier and more sensitive detection of chemotherapy-induced cardiotoxicity may allow improved treatment strategies and increase long-term survival. Lipophilic cation PET tracers may be suitable for early detection of cardiotoxicity. This study aimed to evaluate an
F-labeled lipophilic phosphonium cation, [1-(2-
F-fluoroethyl),1
[1,2,3]triazole-4-ethylene]triphenylphosphonium bromide (
F-MitoPhos), as a cardiac imaging agent, comparing it with leading PET and SPECT lipophilic cationic tracers before further assessing its potential for imaging cardiotoxicity in an acute doxorubicin model.
Cardiac uptake and response to decreased mitochondrial membrane potential of
F-MitoPhos and
Tc-sestamibi were tested in isolated perfused rat hearts. Baseline pharmacokinetic profiles of
F-MitoPhos and
F-fluorobenzyltriphenylphosphonium and their response to acute doxorubicin-induced cardiotoxicity were assessed in rats in vivo (10, 15, or 20 mg of doxorubicin per kilogram, intravenously, 48 h beforehand).
Cardiac retention of
F-MitoPhos was more than double that of
Tc-sestamibi in isolated perfused rat hearts. A favorable biodistribution of
F-MitoPhos in vivo was observed, with heart-to-tissue ratios of 304 ± 186, 11.2 ± 1.2, and 3.8 ± 0.6 for plasma, liver, and lung, respectively (60 min). A significant dose-dependent loss of cardiac retention of
F-MitoPhos was observed on doxorubicin treatment, with average cardiac SUV from 30 to 60 min (mean ± SD) decreasing from 3.5 ± 0.5 (control) to 1.8 ± 0.1 (doxorubicin, 20 mg/kg). Other assessed biomarkers showed no alterations.
F-MitoPhos showed pharmacokinetic parameters suitable for cardiac imaging. A significant dose response of cardiac uptake to doxorubicin treatment was observed before detectable biomarker alterations.
F-MitoPhos is therefore a promising tracer for imaging chemotherapy-induced cardiotoxicity. To our knowledge, this is the first demonstration of radiolabeled lipophilic cations being used for the PET imaging of chemotherapy-induced cardiotoxicity and indicates the potential application of these compounds in this area.</abstract><cop>United States</cop><pmid>31147403</pmid><doi>10.2967/jnumed.119.226787</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0161-5505 |
| ispartof | Journal of Nuclear Medicine, 2019-12, Vol.60 (12), p.1750-1756 |
| issn | 0161-5505 1535-5667 2159-662X |
| language | eng |
| recordid | cdi_crossref_primary_10_2967_jnumed_119_226787 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Antineoplastic Agents - adverse effects Cardiotoxicity - diagnostic imaging Cardiotoxicity - etiology Cardiotoxicity - metabolism Doxorubicin - adverse effects Fluorine Radioisotopes Hydrophobic and Hydrophilic Interactions Isotope Labeling Male Organophosphorus Compounds - chemistry Organophosphorus Compounds - pharmacokinetics Positron-Emission Tomography Rats Rats, Sprague-Dawley Tissue Distribution |
| title | Imaging of Chemotherapy-Induced Acute Cardiotoxicity with 18 F-Labeled Lipophilic Cations |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T01%3A17%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Imaging%20of%20Chemotherapy-Induced%20Acute%20Cardiotoxicity%20with%2018%20F-Labeled%20Lipophilic%20Cations&rft.jtitle=Journal%20of%20Nuclear%20Medicine&rft.au=McCluskey,%20Stuart%20P&rft.date=2019-12&rft.volume=60&rft.issue=12&rft.spage=1750&rft.epage=1756&rft.pages=1750-1756&rft.issn=0161-5505&rft.eissn=1535-5667&rft_id=info:doi/10.2967/jnumed.119.226787&rft_dat=%3Cpubmed_cross%3E31147403%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/31147403&rfr_iscdi=true |