SPECT imaging of fibrin using fibrin-binding peptides
Noninvasive detection of fibrin in vivo using diagnostic imaging modalities may improve clinical decision‐making on possible therapeutic options in atherosclerosis, cancer and thrombus‐related pathologies such as pulmonary embolism and deep venous thrombosis. The aim of this study was to assess the...
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| Veröffentlicht in: | Contrast media and molecular imaging 2013-05, Vol.8 (3), p.229-237 |
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| creator | Starmans, Lucas W. E. van Duijnhoven, Sander M. J. Rossin, Raffaella Aime, Silvio Daemen, Mat J. A. P. Nicolay, Klaas Grüll, Holger |
| description | Noninvasive detection of fibrin in vivo using diagnostic imaging modalities may improve clinical decision‐making on possible therapeutic options in atherosclerosis, cancer and thrombus‐related pathologies such as pulmonary embolism and deep venous thrombosis. The aim of this study was to assess the potential of a novel 111In‐labeled fibrin‐binding peptide (FibPep) to visualize thrombi in mice noninvasively using single‐photon emission computed tomography (SPECT). FibPep and a negative control peptide (NCFibPep) were synthesized and their fibrin‐binding properties were assessed in vitro. FibPep showed enhanced binding compared with NCFibPep to both fibrin and blood clots. FibPep bound to fibrin with a dissociation constant (Kd) of 0.8 μ m, whereas NCFibPep displayed at least a 100‐fold lower affinity towards fibrin. A FeCl3‐injury carotid artery thrombosis mouse model was used to evaluate the peptides in vivo. FibPep and NCFibPep displayed rapid blood clearance and were eliminated via the renal pathway. In vivo SPECT imaging using FibPep allowed clear visualization of thrombi. Ex vivo biodistribution showed significantly increased uptake of FibPep in the thrombus‐containing carotid in comparison to the noninjured carotid (5.7 ± 0.7 and 0.6 ± 0.4% injected dose per gram (%ID g−1), respectively; p |
| doi_str_mv | 10.1002/cmmi.1521 |
| format | Article |
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In this study, we show the potential of a novel 111In‐labeled fibrin‐binding peptide (FibPep) for noninvasive detection of fibrin deposition using SPECT. FibPep and a negative control peptide (NCFibPep) were synthesized and their fibrin‐binding properties were assessed in vitro and in vivo. In vivo SPECT imaging using FibPep allowed clear visualization of thrombi. Ex vivo biodistribution showed significantly increased uptake of FibPep in the thrombus‐containing carotid in comparison to the noninjured carotid, whereas nonspecific NCFibPep did not.</description><identifier>ISSN: 1555-4309</identifier><identifier>EISSN: 1555-4317</identifier><identifier>DOI: 10.1002/cmmi.1521</identifier><identifier>PMID: 23606426</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Animals ; Atherosclerosis ; Blood clots ; Carotid Artery Thrombosis - diagnostic imaging ; Carotid Artery Thrombosis - metabolism ; fibrin ; Fibrin - metabolism ; Indium Radioisotopes - pharmacokinetics ; Isotope Labeling - methods ; Medical imaging ; Metabolic Clearance Rate ; Mice ; Mice, Inbred C57BL ; molecular imaging ; Molecular Imaging - methods ; peptides ; Peptides - chemistry ; Peptides - pharmacokinetics ; Protein Binding ; Radiopharmaceuticals - pharmacokinetics ; Reproducibility of Results ; Sensitivity and Specificity ; SPECT ; Thrombosis ; thrombus ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon - methods</subject><ispartof>Contrast media and molecular imaging, 2013-05, Vol.8 (3), p.229-237</ispartof><rights>Copyright © 2013 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4261-a4babb12cf05275e12c213c77b96e5d5b155b1df42cf75003f178b1ad0b79be13</citedby><cites>FETCH-LOGICAL-c4261-a4babb12cf05275e12c213c77b96e5d5b155b1df42cf75003f178b1ad0b79be13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23606426$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Starmans, Lucas W. E.</creatorcontrib><creatorcontrib>van Duijnhoven, Sander M. J.</creatorcontrib><creatorcontrib>Rossin, Raffaella</creatorcontrib><creatorcontrib>Aime, Silvio</creatorcontrib><creatorcontrib>Daemen, Mat J. A. P.</creatorcontrib><creatorcontrib>Nicolay, Klaas</creatorcontrib><creatorcontrib>Grüll, Holger</creatorcontrib><title>SPECT imaging of fibrin using fibrin-binding peptides</title><title>Contrast media and molecular imaging</title><addtitle>Contrast Media Mol. Imaging</addtitle><description>Noninvasive detection of fibrin in vivo using diagnostic imaging modalities may improve clinical decision‐making on possible therapeutic options in atherosclerosis, cancer and thrombus‐related pathologies such as pulmonary embolism and deep venous thrombosis. The aim of this study was to assess the potential of a novel 111In‐labeled fibrin‐binding peptide (FibPep) to visualize thrombi in mice noninvasively using single‐photon emission computed tomography (SPECT). FibPep and a negative control peptide (NCFibPep) were synthesized and their fibrin‐binding properties were assessed in vitro. FibPep showed enhanced binding compared with NCFibPep to both fibrin and blood clots. FibPep bound to fibrin with a dissociation constant (Kd) of 0.8 μ m, whereas NCFibPep displayed at least a 100‐fold lower affinity towards fibrin. A FeCl3‐injury carotid artery thrombosis mouse model was used to evaluate the peptides in vivo. FibPep and NCFibPep displayed rapid blood clearance and were eliminated via the renal pathway. In vivo SPECT imaging using FibPep allowed clear visualization of thrombi. Ex vivo biodistribution showed significantly increased uptake of FibPep in the thrombus‐containing carotid in comparison to the noninjured carotid (5.7 ± 0.7 and 0.6 ± 0.4% injected dose per gram (%ID g−1), respectively; p < 0.01; n = 4), whereas nonspecific NCFibPep did not (0.4 ± 0.2 and 0.3 ± 0.0%ID g−1, respectively; n = 4). In conclusion, FibPep displayed high affinity towards fibrin in vitro and rapid blood clearance in vivo, and allowed sensitive detection of thrombi using SPECT imaging. Therefore, this particular imaging approach may provide a new tool to diagnose and monitor diseases such as atherosclerosis and cancer. Copyright © 2013 John Wiley & Sons, Ltd.
In this study, we show the potential of a novel 111In‐labeled fibrin‐binding peptide (FibPep) for noninvasive detection of fibrin deposition using SPECT. FibPep and a negative control peptide (NCFibPep) were synthesized and their fibrin‐binding properties were assessed in vitro and in vivo. In vivo SPECT imaging using FibPep allowed clear visualization of thrombi. Ex vivo biodistribution showed significantly increased uptake of FibPep in the thrombus‐containing carotid in comparison to the noninjured carotid, whereas nonspecific NCFibPep did not.</description><subject>Animals</subject><subject>Atherosclerosis</subject><subject>Blood clots</subject><subject>Carotid Artery Thrombosis - diagnostic imaging</subject><subject>Carotid Artery Thrombosis - metabolism</subject><subject>fibrin</subject><subject>Fibrin - metabolism</subject><subject>Indium Radioisotopes - pharmacokinetics</subject><subject>Isotope Labeling - methods</subject><subject>Medical imaging</subject><subject>Metabolic Clearance Rate</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>molecular imaging</subject><subject>Molecular Imaging - methods</subject><subject>peptides</subject><subject>Peptides - chemistry</subject><subject>Peptides - pharmacokinetics</subject><subject>Protein Binding</subject><subject>Radiopharmaceuticals - pharmacokinetics</subject><subject>Reproducibility of Results</subject><subject>Sensitivity and Specificity</subject><subject>SPECT</subject><subject>Thrombosis</subject><subject>thrombus</subject><subject>Tissue Distribution</subject><subject>Tomography, Emission-Computed, Single-Photon - methods</subject><issn>1555-4309</issn><issn>1555-4317</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE9LwzAYh4Mobk4PfgEpeNFDt6RJmuUoZW6DTQdOdgxNm47M_jNZ0X17Uzp3EDzl_cHzPrz5AXCL4BBBGIySotBDRAN0BvqIUuoTjNj5aYa8B66s3UFICOb4EvQCHMKQBGEf0LfVJFp7uoi3utx6VeZlWhpdeo1tcxd8qcu0jbWq9zpV9hpcZHFu1c3xHYD358k6mvmL1-k8elr4iZMjPyYylhIFSQZpwKhyU4BwwpjkoaIple5AidKMOIJRCHGG2FiiOIWScakQHoCHzlub6rNRdi8KbROV53GpqsYKhPEYc0Qwc-j9H3RXNaZ017UU5JxDGDrqsaMSU1lrVCZq4_5uDgJB0XYp2i5F26Vj747GRhYqPZG_5Tlg1AFfOleH_00iWi7nR6XfbWi7V9-njdh8iJBhRsXmZSowITOyWYVijH8AmLCKew</recordid><startdate>201305</startdate><enddate>201305</enddate><creator>Starmans, Lucas W. E.</creator><creator>van Duijnhoven, Sander M. J.</creator><creator>Rossin, Raffaella</creator><creator>Aime, Silvio</creator><creator>Daemen, Mat J. A. P.</creator><creator>Nicolay, Klaas</creator><creator>Grüll, Holger</creator><general>Blackwell Publishing Ltd</general><general>Hindawi Limited</general><scope>BSCLL</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>7QO</scope><scope>7QP</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201305</creationdate><title>SPECT imaging of fibrin using fibrin-binding peptides</title><author>Starmans, Lucas W. E. ; van Duijnhoven, Sander M. J. ; Rossin, Raffaella ; Aime, Silvio ; Daemen, Mat J. A. P. ; Nicolay, Klaas ; Grüll, Holger</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4261-a4babb12cf05275e12c213c77b96e5d5b155b1df42cf75003f178b1ad0b79be13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Atherosclerosis</topic><topic>Blood clots</topic><topic>Carotid Artery Thrombosis - diagnostic imaging</topic><topic>Carotid Artery Thrombosis - metabolism</topic><topic>fibrin</topic><topic>Fibrin - metabolism</topic><topic>Indium Radioisotopes - pharmacokinetics</topic><topic>Isotope Labeling - methods</topic><topic>Medical imaging</topic><topic>Metabolic Clearance Rate</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>molecular imaging</topic><topic>Molecular Imaging - methods</topic><topic>peptides</topic><topic>Peptides - chemistry</topic><topic>Peptides - pharmacokinetics</topic><topic>Protein Binding</topic><topic>Radiopharmaceuticals - pharmacokinetics</topic><topic>Reproducibility of Results</topic><topic>Sensitivity and Specificity</topic><topic>SPECT</topic><topic>Thrombosis</topic><topic>thrombus</topic><topic>Tissue Distribution</topic><topic>Tomography, Emission-Computed, Single-Photon - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Starmans, Lucas W. E.</creatorcontrib><creatorcontrib>van Duijnhoven, Sander M. J.</creatorcontrib><creatorcontrib>Rossin, Raffaella</creatorcontrib><creatorcontrib>Aime, Silvio</creatorcontrib><creatorcontrib>Daemen, Mat J. A. P.</creatorcontrib><creatorcontrib>Nicolay, Klaas</creatorcontrib><creatorcontrib>Grüll, Holger</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Contrast media and molecular imaging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Starmans, Lucas W. E.</au><au>van Duijnhoven, Sander M. J.</au><au>Rossin, Raffaella</au><au>Aime, Silvio</au><au>Daemen, Mat J. A. P.</au><au>Nicolay, Klaas</au><au>Grüll, Holger</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SPECT imaging of fibrin using fibrin-binding peptides</atitle><jtitle>Contrast media and molecular imaging</jtitle><addtitle>Contrast Media Mol. Imaging</addtitle><date>2013-05</date><risdate>2013</risdate><volume>8</volume><issue>3</issue><spage>229</spage><epage>237</epage><pages>229-237</pages><issn>1555-4309</issn><eissn>1555-4317</eissn><abstract>Noninvasive detection of fibrin in vivo using diagnostic imaging modalities may improve clinical decision‐making on possible therapeutic options in atherosclerosis, cancer and thrombus‐related pathologies such as pulmonary embolism and deep venous thrombosis. The aim of this study was to assess the potential of a novel 111In‐labeled fibrin‐binding peptide (FibPep) to visualize thrombi in mice noninvasively using single‐photon emission computed tomography (SPECT). FibPep and a negative control peptide (NCFibPep) were synthesized and their fibrin‐binding properties were assessed in vitro. FibPep showed enhanced binding compared with NCFibPep to both fibrin and blood clots. FibPep bound to fibrin with a dissociation constant (Kd) of 0.8 μ m, whereas NCFibPep displayed at least a 100‐fold lower affinity towards fibrin. A FeCl3‐injury carotid artery thrombosis mouse model was used to evaluate the peptides in vivo. FibPep and NCFibPep displayed rapid blood clearance and were eliminated via the renal pathway. In vivo SPECT imaging using FibPep allowed clear visualization of thrombi. Ex vivo biodistribution showed significantly increased uptake of FibPep in the thrombus‐containing carotid in comparison to the noninjured carotid (5.7 ± 0.7 and 0.6 ± 0.4% injected dose per gram (%ID g−1), respectively; p < 0.01; n = 4), whereas nonspecific NCFibPep did not (0.4 ± 0.2 and 0.3 ± 0.0%ID g−1, respectively; n = 4). In conclusion, FibPep displayed high affinity towards fibrin in vitro and rapid blood clearance in vivo, and allowed sensitive detection of thrombi using SPECT imaging. Therefore, this particular imaging approach may provide a new tool to diagnose and monitor diseases such as atherosclerosis and cancer. Copyright © 2013 John Wiley & Sons, Ltd.
In this study, we show the potential of a novel 111In‐labeled fibrin‐binding peptide (FibPep) for noninvasive detection of fibrin deposition using SPECT. FibPep and a negative control peptide (NCFibPep) were synthesized and their fibrin‐binding properties were assessed in vitro and in vivo. In vivo SPECT imaging using FibPep allowed clear visualization of thrombi. Ex vivo biodistribution showed significantly increased uptake of FibPep in the thrombus‐containing carotid in comparison to the noninjured carotid, whereas nonspecific NCFibPep did not.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>23606426</pmid><doi>10.1002/cmmi.1521</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Atherosclerosis Blood clots Carotid Artery Thrombosis - diagnostic imaging Carotid Artery Thrombosis - metabolism fibrin Fibrin - metabolism Indium Radioisotopes - pharmacokinetics Isotope Labeling - methods Medical imaging Metabolic Clearance Rate Mice Mice, Inbred C57BL molecular imaging Molecular Imaging - methods peptides Peptides - chemistry Peptides - pharmacokinetics Protein Binding Radiopharmaceuticals - pharmacokinetics Reproducibility of Results Sensitivity and Specificity SPECT Thrombosis thrombus Tissue Distribution Tomography, Emission-Computed, Single-Photon - methods |
| title | SPECT imaging of fibrin using fibrin-binding peptides |
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