Detecting Validated Intracellular ROS Generation with 18 F-dihydroethidine-Based PET
To determine the sensitivity of the F-radiolabelled dihydroethidine analogue ([ F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress. The sensitivity of [ F]DHE to various ROS-generating systems was first established in vitro. Then, isolated rat hearts were perfused under constant f...
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| Veröffentlicht in: | Molecular imaging and biology 2022-06, Vol.24 (3), p.377 |
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| container_title | Molecular imaging and biology |
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| creator | Waters, Edward C T Baark, Friedrich Yu, Zilin Mota, Filipa Eykyn, Thomas R Yan, Ran Southworth, Richard |
| description | To determine the sensitivity of the
F-radiolabelled dihydroethidine analogue ([
F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress.
The sensitivity of [
F]DHE to various ROS-generating systems was first established in vitro. Then, isolated rat hearts were perfused under constant flow, with contractile function monitored by intraventricular balloon. Cardiac uptake of infused [
F]DHE (50-150 kBq.min
) was monitored by γ-detection, while ROS generation was invoked by menadione infusion (0, 10, or 50 μm), validated by parallel measures of cardiac oxidative stress.
[
F]DHE was most sensitive to oxidation by superoxide and hydroxyl radicals. Normalised [
F]DHE uptake was significantly greater in menadione-treated hearts (1.44 ± 0.27) versus control (0.81 ± 0.07) (p |
| doi_str_mv | 10.1007/s11307-021-01683-0 |
| format | Article |
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F-radiolabelled dihydroethidine analogue ([
F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress.
The sensitivity of [
F]DHE to various ROS-generating systems was first established in vitro. Then, isolated rat hearts were perfused under constant flow, with contractile function monitored by intraventricular balloon. Cardiac uptake of infused [
F]DHE (50-150 kBq.min
) was monitored by γ-detection, while ROS generation was invoked by menadione infusion (0, 10, or 50 μm), validated by parallel measures of cardiac oxidative stress.
[
F]DHE was most sensitive to oxidation by superoxide and hydroxyl radicals. Normalised [
F]DHE uptake was significantly greater in menadione-treated hearts (1.44 ± 0.27) versus control (0.81 ± 0.07) (p < 0.05, n = 4/group), associated with concomitant cardiac contractile dysfunction, glutathione depletion, and PKG1α dimerisation.
[
F]DHE reports on ROS in a validated model of oxidative stress where perfusion (and tracer delivery) is unlikely to impact its pharmacokinetics.</description><identifier>EISSN: 1860-2002</identifier><identifier>DOI: 10.1007/s11307-021-01683-0</identifier><identifier>PMID: 34820762</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Dicarbethoxydihydrocollidine - analogs & derivatives ; Positron-Emission Tomography ; Rats ; Reactive Oxygen Species ; Vitamin K 3</subject><ispartof>Molecular imaging and biology, 2022-06, Vol.24 (3), p.377</ispartof><rights>2021. Crown.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-7904-8335</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34820762$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Waters, Edward C T</creatorcontrib><creatorcontrib>Baark, Friedrich</creatorcontrib><creatorcontrib>Yu, Zilin</creatorcontrib><creatorcontrib>Mota, Filipa</creatorcontrib><creatorcontrib>Eykyn, Thomas R</creatorcontrib><creatorcontrib>Yan, Ran</creatorcontrib><creatorcontrib>Southworth, Richard</creatorcontrib><title>Detecting Validated Intracellular ROS Generation with 18 F-dihydroethidine-Based PET</title><title>Molecular imaging and biology</title><addtitle>Mol Imaging Biol</addtitle><description>To determine the sensitivity of the
F-radiolabelled dihydroethidine analogue ([
F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress.
The sensitivity of [
F]DHE to various ROS-generating systems was first established in vitro. Then, isolated rat hearts were perfused under constant flow, with contractile function monitored by intraventricular balloon. Cardiac uptake of infused [
F]DHE (50-150 kBq.min
) was monitored by γ-detection, while ROS generation was invoked by menadione infusion (0, 10, or 50 μm), validated by parallel measures of cardiac oxidative stress.
[
F]DHE was most sensitive to oxidation by superoxide and hydroxyl radicals. Normalised [
F]DHE uptake was significantly greater in menadione-treated hearts (1.44 ± 0.27) versus control (0.81 ± 0.07) (p < 0.05, n = 4/group), associated with concomitant cardiac contractile dysfunction, glutathione depletion, and PKG1α dimerisation.
[
F]DHE reports on ROS in a validated model of oxidative stress where perfusion (and tracer delivery) is unlikely to impact its pharmacokinetics.</description><subject>Animals</subject><subject>Dicarbethoxydihydrocollidine - analogs & derivatives</subject><subject>Positron-Emission Tomography</subject><subject>Rats</subject><subject>Reactive Oxygen Species</subject><subject>Vitamin K 3</subject><issn>1860-2002</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFjrFuwjAUAK1KiADlBzog_4Db92yUZC5NKFOrEnVFBr82rhwT2Y4q_h4GmJluuZOOsSeEZwQoXiKigkKARAGYl0rAA5tgmYOQADJj0xj_ALBAqcYsU8tSQpHLCWveKNEhWf_Lv7WzRicyfONT0AdybnA68K-PLV-Tp6CTPXr-b1PLseS1MLY9mXCk1FpjPYlXHS_xZ9U8stGPdpHmV87Yoq6a1bvoh31HZtcH2-lw2t021F3hDOzcQhE</recordid><startdate>202206</startdate><enddate>202206</enddate><creator>Waters, Edward C T</creator><creator>Baark, Friedrich</creator><creator>Yu, Zilin</creator><creator>Mota, Filipa</creator><creator>Eykyn, Thomas R</creator><creator>Yan, Ran</creator><creator>Southworth, Richard</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><orcidid>https://orcid.org/0000-0002-7904-8335</orcidid></search><sort><creationdate>202206</creationdate><title>Detecting Validated Intracellular ROS Generation with 18 F-dihydroethidine-Based PET</title><author>Waters, Edward C T ; Baark, Friedrich ; Yu, Zilin ; Mota, Filipa ; Eykyn, Thomas R ; Yan, Ran ; Southworth, Richard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmed_primary_348207623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Dicarbethoxydihydrocollidine - analogs & derivatives</topic><topic>Positron-Emission Tomography</topic><topic>Rats</topic><topic>Reactive Oxygen Species</topic><topic>Vitamin K 3</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Waters, Edward C T</creatorcontrib><creatorcontrib>Baark, Friedrich</creatorcontrib><creatorcontrib>Yu, Zilin</creatorcontrib><creatorcontrib>Mota, Filipa</creatorcontrib><creatorcontrib>Eykyn, Thomas R</creatorcontrib><creatorcontrib>Yan, Ran</creatorcontrib><creatorcontrib>Southworth, Richard</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Molecular imaging and biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Waters, Edward C T</au><au>Baark, Friedrich</au><au>Yu, Zilin</au><au>Mota, Filipa</au><au>Eykyn, Thomas R</au><au>Yan, Ran</au><au>Southworth, Richard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Detecting Validated Intracellular ROS Generation with 18 F-dihydroethidine-Based PET</atitle><jtitle>Molecular imaging and biology</jtitle><addtitle>Mol Imaging Biol</addtitle><date>2022-06</date><risdate>2022</risdate><volume>24</volume><issue>3</issue><spage>377</spage><pages>377-</pages><eissn>1860-2002</eissn><abstract>To determine the sensitivity of the
F-radiolabelled dihydroethidine analogue ([
F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress.
The sensitivity of [
F]DHE to various ROS-generating systems was first established in vitro. Then, isolated rat hearts were perfused under constant flow, with contractile function monitored by intraventricular balloon. Cardiac uptake of infused [
F]DHE (50-150 kBq.min
) was monitored by γ-detection, while ROS generation was invoked by menadione infusion (0, 10, or 50 μm), validated by parallel measures of cardiac oxidative stress.
[
F]DHE was most sensitive to oxidation by superoxide and hydroxyl radicals. Normalised [
F]DHE uptake was significantly greater in menadione-treated hearts (1.44 ± 0.27) versus control (0.81 ± 0.07) (p < 0.05, n = 4/group), associated with concomitant cardiac contractile dysfunction, glutathione depletion, and PKG1α dimerisation.
[
F]DHE reports on ROS in a validated model of oxidative stress where perfusion (and tracer delivery) is unlikely to impact its pharmacokinetics.</abstract><cop>United States</cop><pmid>34820762</pmid><doi>10.1007/s11307-021-01683-0</doi><orcidid>https://orcid.org/0000-0002-7904-8335</orcidid></addata></record> |
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| identifier | EISSN: 1860-2002 |
| ispartof | Molecular imaging and biology, 2022-06, Vol.24 (3), p.377 |
| issn | 1860-2002 |
| language | eng |
| recordid | cdi_pubmed_primary_34820762 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Animals Dicarbethoxydihydrocollidine - analogs & derivatives Positron-Emission Tomography Rats Reactive Oxygen Species Vitamin K 3 |
| title | Detecting Validated Intracellular ROS Generation with 18 F-dihydroethidine-Based PET |
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