18 F-GP1, a Novel PET Tracer Designed for High-Sensitivity, Low-Background Detection of Thrombi
Thromboembolic diseases such as myocardial infarction, stroke, transient ischemic attacks, and pulmonary embolism are major causes of morbidity and mortality worldwide. Glycoprotein IIb/IIIa (GPIIb/IIIa) is the key receptor involved in platelet aggregation and is a validated target for therapeutic a...
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| Veröffentlicht in: | Journal of Nuclear Medicine 2017-07, Vol.58 (7), p.1094-1099 |
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| creator | Lohrke, Jessica Siebeneicher, Holger Berger, Markus Reinhardt, Michael Berndt, Mathias Mueller, Andre Zerna, Marion Koglin, Norman Oden, Felix Bauser, Marcus Friebe, Matthias Dinkelborg, Ludger M Huetter, Joachim Stephens, Andrew W |
| description | Thromboembolic diseases such as myocardial infarction, stroke, transient ischemic attacks, and pulmonary embolism are major causes of morbidity and mortality worldwide. Glycoprotein IIb/IIIa (GPIIb/IIIa) is the key receptor involved in platelet aggregation and is a validated target for therapeutic approaches and diagnostic imaging. The aim of this study was to develop and characterize a specific small-molecule tracer for PET imaging that binds with high affinity to GPIIb/IIIa receptors and has suitable pharmacokinetic properties to overcome limitations of previous approaches.
Binding of
F-GP1 to GPIIb/IIIa receptors was investigated in competition binding assays and autoradiography using a fresh cardiac thrombus from an explanted human heart. The clot-to-blood ratio for
F-GP1 was investigated by an in vitro blood flow model. Biodistribution and thrombus detection was investigated in cynomolgus monkeys after insertion of a roughened catheter into either the vena cava or the aorta.
F-GP1 is an
F-labeled small molecule for PET imaging of thrombi. The half maximal inhibitory concentration of
F-GP1 to GPIIb/IIIa was 20 nM.
F-GP1 bound to thrombi with a mean clot-to-blood ratio of 95. Binding was specific and can be displaced by excess nonradioactive derivative. Binding was not affected by anticoagulants such as aspirin or heparin.
F-GP1 showed rapid blood clearance and a low background after intravenous injection in cynomolgus monkeys. Small arterial, venous thrombi, thrombotic depositions on damaged endothelial surface, and small cerebral emboli were detected in vivo by PET imaging.
F-GP1 binds specifically with high affinity to the GPIIb/IIIa receptor involved in platelet aggregation. Because of its favorable preclinical characteristics,
F-GP1 is currently being investigated in a human clinical study. |
| doi_str_mv | 10.2967/jnumed.116.188896 |
| format | Article |
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Binding of
F-GP1 to GPIIb/IIIa receptors was investigated in competition binding assays and autoradiography using a fresh cardiac thrombus from an explanted human heart. The clot-to-blood ratio for
F-GP1 was investigated by an in vitro blood flow model. Biodistribution and thrombus detection was investigated in cynomolgus monkeys after insertion of a roughened catheter into either the vena cava or the aorta.
F-GP1 is an
F-labeled small molecule for PET imaging of thrombi. The half maximal inhibitory concentration of
F-GP1 to GPIIb/IIIa was 20 nM.
F-GP1 bound to thrombi with a mean clot-to-blood ratio of 95. Binding was specific and can be displaced by excess nonradioactive derivative. Binding was not affected by anticoagulants such as aspirin or heparin.
F-GP1 showed rapid blood clearance and a low background after intravenous injection in cynomolgus monkeys. Small arterial, venous thrombi, thrombotic depositions on damaged endothelial surface, and small cerebral emboli were detected in vivo by PET imaging.
F-GP1 binds specifically with high affinity to the GPIIb/IIIa receptor involved in platelet aggregation. Because of its favorable preclinical characteristics,
F-GP1 is currently being investigated in a human clinical study.</description><identifier>ISSN: 0161-5505</identifier><identifier>EISSN: 1535-5667</identifier><identifier>EISSN: 2159-662X</identifier><identifier>DOI: 10.2967/jnumed.116.188896</identifier><identifier>PMID: 28302764</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Female ; Fluorine Radioisotopes - chemistry ; Fluorine Radioisotopes - pharmacokinetics ; Glutamine - analogs & derivatives ; Glutamine - pharmacokinetics ; Humans ; Isotope Labeling - methods ; Laurates - pharmacokinetics ; Macaca fascicularis ; Molecular Imaging - methods ; Platelet Glycoprotein GPIIb-IIIa Complex - metabolism ; Positron-Emission Tomography - methods ; Radiopharmaceuticals - chemical synthesis ; Radiopharmaceuticals - pharmacokinetics ; Reproducibility of Results ; Sensitivity and Specificity ; Thrombosis - diagnostic imaging ; Thrombosis - metabolism</subject><ispartof>Journal of Nuclear Medicine, 2017-07, Vol.58 (7), p.1094-1099</ispartof><rights>2017 by the Society of Nuclear Medicine and Molecular Imaging.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1134-7e6699cdf3182a3765b658508fb788de0d2470ab614658794fad463c14376fe3</citedby><cites>FETCH-LOGICAL-c1134-7e6699cdf3182a3765b658508fb788de0d2470ab614658794fad463c14376fe3</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/28302764$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lohrke, Jessica</creatorcontrib><creatorcontrib>Siebeneicher, Holger</creatorcontrib><creatorcontrib>Berger, Markus</creatorcontrib><creatorcontrib>Reinhardt, Michael</creatorcontrib><creatorcontrib>Berndt, Mathias</creatorcontrib><creatorcontrib>Mueller, Andre</creatorcontrib><creatorcontrib>Zerna, Marion</creatorcontrib><creatorcontrib>Koglin, Norman</creatorcontrib><creatorcontrib>Oden, Felix</creatorcontrib><creatorcontrib>Bauser, Marcus</creatorcontrib><creatorcontrib>Friebe, Matthias</creatorcontrib><creatorcontrib>Dinkelborg, Ludger M</creatorcontrib><creatorcontrib>Huetter, Joachim</creatorcontrib><creatorcontrib>Stephens, Andrew W</creatorcontrib><title>18 F-GP1, a Novel PET Tracer Designed for High-Sensitivity, Low-Background Detection of Thrombi</title><title>Journal of Nuclear Medicine</title><addtitle>J Nucl Med</addtitle><description>Thromboembolic diseases such as myocardial infarction, stroke, transient ischemic attacks, and pulmonary embolism are major causes of morbidity and mortality worldwide. Glycoprotein IIb/IIIa (GPIIb/IIIa) is the key receptor involved in platelet aggregation and is a validated target for therapeutic approaches and diagnostic imaging. The aim of this study was to develop and characterize a specific small-molecule tracer for PET imaging that binds with high affinity to GPIIb/IIIa receptors and has suitable pharmacokinetic properties to overcome limitations of previous approaches.
Binding of
F-GP1 to GPIIb/IIIa receptors was investigated in competition binding assays and autoradiography using a fresh cardiac thrombus from an explanted human heart. The clot-to-blood ratio for
F-GP1 was investigated by an in vitro blood flow model. Biodistribution and thrombus detection was investigated in cynomolgus monkeys after insertion of a roughened catheter into either the vena cava or the aorta.
F-GP1 is an
F-labeled small molecule for PET imaging of thrombi. The half maximal inhibitory concentration of
F-GP1 to GPIIb/IIIa was 20 nM.
F-GP1 bound to thrombi with a mean clot-to-blood ratio of 95. Binding was specific and can be displaced by excess nonradioactive derivative. Binding was not affected by anticoagulants such as aspirin or heparin.
F-GP1 showed rapid blood clearance and a low background after intravenous injection in cynomolgus monkeys. Small arterial, venous thrombi, thrombotic depositions on damaged endothelial surface, and small cerebral emboli were detected in vivo by PET imaging.
F-GP1 binds specifically with high affinity to the GPIIb/IIIa receptor involved in platelet aggregation. Because of its favorable preclinical characteristics,
F-GP1 is currently being investigated in a human clinical study.</description><subject>Animals</subject><subject>Female</subject><subject>Fluorine Radioisotopes - chemistry</subject><subject>Fluorine Radioisotopes - pharmacokinetics</subject><subject>Glutamine - analogs & derivatives</subject><subject>Glutamine - pharmacokinetics</subject><subject>Humans</subject><subject>Isotope Labeling - methods</subject><subject>Laurates - pharmacokinetics</subject><subject>Macaca fascicularis</subject><subject>Molecular Imaging - methods</subject><subject>Platelet Glycoprotein GPIIb-IIIa Complex - metabolism</subject><subject>Positron-Emission Tomography - methods</subject><subject>Radiopharmaceuticals - chemical synthesis</subject><subject>Radiopharmaceuticals - pharmacokinetics</subject><subject>Reproducibility of Results</subject><subject>Sensitivity and Specificity</subject><subject>Thrombosis - diagnostic imaging</subject><subject>Thrombosis - metabolism</subject><issn>0161-5505</issn><issn>1535-5667</issn><issn>2159-662X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kF1PwjAUQBujEUR_gC-mP4Bi77p-7FH5NCFK4t6XbmuhCCvpBoZ_78jk6Sb3nnMfDkLPQEdRIuTrtjruTTkCECNQSiXiBvWBM064EPIW9SkIIJxT3kMPdb2llIoWu0e9SDEaSRH3UQYKz8h8BUOs8ac_mR1eTVOcBl2YgCemduvKlNj6gBduvSHfpqpd406uOQ_x0v-Sd138rIM_VmVLN6ZonK-wtzjdBL_P3SO6s3pXm6f_OUDpbJqOF2T5Nf8Yvy1JAcBiIo0QSVKUloGKNJOC54IrTpXNpVKloWUUS6pzAXG7l0lsdRkLVkDcstawAYLubRF8XQdjs0Nwex3OGdDs0irrWmVtq6xr1TovnXM45pfT1bjGYX89GGQc</recordid><startdate>201707</startdate><enddate>201707</enddate><creator>Lohrke, Jessica</creator><creator>Siebeneicher, Holger</creator><creator>Berger, Markus</creator><creator>Reinhardt, Michael</creator><creator>Berndt, Mathias</creator><creator>Mueller, Andre</creator><creator>Zerna, Marion</creator><creator>Koglin, Norman</creator><creator>Oden, Felix</creator><creator>Bauser, Marcus</creator><creator>Friebe, Matthias</creator><creator>Dinkelborg, Ludger M</creator><creator>Huetter, Joachim</creator><creator>Stephens, Andrew W</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>201707</creationdate><title>18 F-GP1, a Novel PET Tracer Designed for High-Sensitivity, Low-Background Detection of Thrombi</title><author>Lohrke, Jessica ; Siebeneicher, Holger ; Berger, Markus ; Reinhardt, Michael ; Berndt, Mathias ; Mueller, Andre ; Zerna, Marion ; Koglin, Norman ; Oden, Felix ; Bauser, Marcus ; Friebe, Matthias ; Dinkelborg, Ludger M ; Huetter, Joachim ; Stephens, Andrew W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1134-7e6699cdf3182a3765b658508fb788de0d2470ab614658794fad463c14376fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Female</topic><topic>Fluorine Radioisotopes - chemistry</topic><topic>Fluorine Radioisotopes - pharmacokinetics</topic><topic>Glutamine - analogs & derivatives</topic><topic>Glutamine - pharmacokinetics</topic><topic>Humans</topic><topic>Isotope Labeling - methods</topic><topic>Laurates - pharmacokinetics</topic><topic>Macaca fascicularis</topic><topic>Molecular Imaging - methods</topic><topic>Platelet Glycoprotein GPIIb-IIIa Complex - metabolism</topic><topic>Positron-Emission Tomography - methods</topic><topic>Radiopharmaceuticals - chemical synthesis</topic><topic>Radiopharmaceuticals - pharmacokinetics</topic><topic>Reproducibility of Results</topic><topic>Sensitivity and Specificity</topic><topic>Thrombosis - diagnostic imaging</topic><topic>Thrombosis - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lohrke, Jessica</creatorcontrib><creatorcontrib>Siebeneicher, Holger</creatorcontrib><creatorcontrib>Berger, Markus</creatorcontrib><creatorcontrib>Reinhardt, Michael</creatorcontrib><creatorcontrib>Berndt, Mathias</creatorcontrib><creatorcontrib>Mueller, Andre</creatorcontrib><creatorcontrib>Zerna, Marion</creatorcontrib><creatorcontrib>Koglin, Norman</creatorcontrib><creatorcontrib>Oden, Felix</creatorcontrib><creatorcontrib>Bauser, Marcus</creatorcontrib><creatorcontrib>Friebe, Matthias</creatorcontrib><creatorcontrib>Dinkelborg, Ludger M</creatorcontrib><creatorcontrib>Huetter, Joachim</creatorcontrib><creatorcontrib>Stephens, Andrew W</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>Lohrke, Jessica</au><au>Siebeneicher, Holger</au><au>Berger, Markus</au><au>Reinhardt, Michael</au><au>Berndt, Mathias</au><au>Mueller, Andre</au><au>Zerna, Marion</au><au>Koglin, Norman</au><au>Oden, Felix</au><au>Bauser, Marcus</au><au>Friebe, Matthias</au><au>Dinkelborg, Ludger M</au><au>Huetter, Joachim</au><au>Stephens, Andrew W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>18 F-GP1, a Novel PET Tracer Designed for High-Sensitivity, Low-Background Detection of Thrombi</atitle><jtitle>Journal of Nuclear Medicine</jtitle><addtitle>J Nucl Med</addtitle><date>2017-07</date><risdate>2017</risdate><volume>58</volume><issue>7</issue><spage>1094</spage><epage>1099</epage><pages>1094-1099</pages><issn>0161-5505</issn><eissn>1535-5667</eissn><eissn>2159-662X</eissn><abstract>Thromboembolic diseases such as myocardial infarction, stroke, transient ischemic attacks, and pulmonary embolism are major causes of morbidity and mortality worldwide. Glycoprotein IIb/IIIa (GPIIb/IIIa) is the key receptor involved in platelet aggregation and is a validated target for therapeutic approaches and diagnostic imaging. The aim of this study was to develop and characterize a specific small-molecule tracer for PET imaging that binds with high affinity to GPIIb/IIIa receptors and has suitable pharmacokinetic properties to overcome limitations of previous approaches.
Binding of
F-GP1 to GPIIb/IIIa receptors was investigated in competition binding assays and autoradiography using a fresh cardiac thrombus from an explanted human heart. The clot-to-blood ratio for
F-GP1 was investigated by an in vitro blood flow model. Biodistribution and thrombus detection was investigated in cynomolgus monkeys after insertion of a roughened catheter into either the vena cava or the aorta.
F-GP1 is an
F-labeled small molecule for PET imaging of thrombi. The half maximal inhibitory concentration of
F-GP1 to GPIIb/IIIa was 20 nM.
F-GP1 bound to thrombi with a mean clot-to-blood ratio of 95. Binding was specific and can be displaced by excess nonradioactive derivative. Binding was not affected by anticoagulants such as aspirin or heparin.
F-GP1 showed rapid blood clearance and a low background after intravenous injection in cynomolgus monkeys. Small arterial, venous thrombi, thrombotic depositions on damaged endothelial surface, and small cerebral emboli were detected in vivo by PET imaging.
F-GP1 binds specifically with high affinity to the GPIIb/IIIa receptor involved in platelet aggregation. Because of its favorable preclinical characteristics,
F-GP1 is currently being investigated in a human clinical study.</abstract><cop>United States</cop><pmid>28302764</pmid><doi>10.2967/jnumed.116.188896</doi><tpages>6</tpages></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Female Fluorine Radioisotopes - chemistry Fluorine Radioisotopes - pharmacokinetics Glutamine - analogs & derivatives Glutamine - pharmacokinetics Humans Isotope Labeling - methods Laurates - pharmacokinetics Macaca fascicularis Molecular Imaging - methods Platelet Glycoprotein GPIIb-IIIa Complex - metabolism Positron-Emission Tomography - methods Radiopharmaceuticals - chemical synthesis Radiopharmaceuticals - pharmacokinetics Reproducibility of Results Sensitivity and Specificity Thrombosis - diagnostic imaging Thrombosis - metabolism |
| title | 18 F-GP1, a Novel PET Tracer Designed for High-Sensitivity, Low-Background Detection of Thrombi |
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