Synthesis, 68Ga labeling and preliminary evaluation of DOTA peptide binding vascular adhesion protein-1: a potential PET imaging agent for diagnosing osteomyelitis
Vascular adhesion protein-1 (VAP-1) is an infection/inflammation-inducible endothelial glycoprotein. Based on our previous studies, the most VAP-1-selective peptide (VAP-P1) was 1,4,7,10-tetraazacyclododecane- N′, N″, N‴, N⁗-tetraacetic acid (DOTA)-conjugated, 68gallium ( 68Ga)-labeled (named [ 68Ga...
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| Veröffentlicht in: | Nuclear medicine and biology 2009-08, Vol.36 (6), p.631-641 |
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| creator | Ujula, Tiina Salomäki, Satu Virsu, Pauliina Lankinen, Petteri Mäkinen, Tatu J. Autio, Anu Yegutkin, Gennady G. Knuuti, Juhani Jalkanen, Sirpa Roivainen, Anne |
| description | Vascular adhesion protein-1 (VAP-1) is an infection/inflammation-inducible endothelial glycoprotein. Based on our previous studies, the most VAP-1-selective peptide (VAP-P1) was 1,4,7,10-tetraazacyclododecane-
N′,
N″,
N‴,
N⁗-tetraacetic acid (DOTA)-conjugated,
68gallium (
68Ga)-labeled (named [
68Ga]DOTAVAP-P1) and evaluated preliminarily.
Targeting was evaluated by using VAP-1-transfected cells. Biodistribution of [
68Ga]DOTAVAP-P1 was studied by positron emission tomography imaging of healthy rats and rats with bone inflammation caused by
Staphylococcus aureus infection. Uptake of [
68Ga]DOTAVAP-P1 in osteomyelitis was compared with negative control peptide and competition with an excess of unlabeled DOTAVAP-P1.
[
68Ga]DOTAVAP-P1 bound more efficiently to VAP-1-transfected cells than to controls. In rats, [
68Ga]DOTAVAP-P1 cleared rapidly from blood circulation, excreted quickly in urine and showed an in vivo half-life of 26±2.3 min. Imaging of osteomyelitis demonstrated modest target-to-background ratio. Studies with the negative control peptide and competitors revealed a significantly lower uptake at the infection site compared to [
68Ga]DOTAVAP-P1.
The results represent a proof-of-concept that infection-induced VAP-1 can be targeted by [
68Ga]DOTA peptide. [
68Ga]DOTAVAP-P1 is just the first candidate peptide and an essential opening for developing VAP-1-specific imaging agents. |
| doi_str_mv | 10.1016/j.nucmedbio.2009.04.008 |
| format | Article |
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N′,
N″,
N‴,
N⁗-tetraacetic acid (DOTA)-conjugated,
68gallium (
68Ga)-labeled (named [
68Ga]DOTAVAP-P1) and evaluated preliminarily.
Targeting was evaluated by using VAP-1-transfected cells. Biodistribution of [
68Ga]DOTAVAP-P1 was studied by positron emission tomography imaging of healthy rats and rats with bone inflammation caused by
Staphylococcus aureus infection. Uptake of [
68Ga]DOTAVAP-P1 in osteomyelitis was compared with negative control peptide and competition with an excess of unlabeled DOTAVAP-P1.
[
68Ga]DOTAVAP-P1 bound more efficiently to VAP-1-transfected cells than to controls. In rats, [
68Ga]DOTAVAP-P1 cleared rapidly from blood circulation, excreted quickly in urine and showed an in vivo half-life of 26±2.3 min. Imaging of osteomyelitis demonstrated modest target-to-background ratio. Studies with the negative control peptide and competitors revealed a significantly lower uptake at the infection site compared to [
68Ga]DOTAVAP-P1.
The results represent a proof-of-concept that infection-induced VAP-1 can be targeted by [
68Ga]DOTA peptide. [
68Ga]DOTAVAP-P1 is just the first candidate peptide and an essential opening for developing VAP-1-specific imaging agents.</description><identifier>ISSN: 0969-8051</identifier><identifier>EISSN: 1872-9614</identifier><identifier>DOI: 10.1016/j.nucmedbio.2009.04.008</identifier><identifier>PMID: 19647169</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>68Gallium ; Amine Oxidase (Copper-Containing) - metabolism ; Amino Acid Sequence ; Animals ; Cell Adhesion Molecules - metabolism ; CHO Cells ; Cricetinae ; Cricetulus ; DOTA peptide ; Experimental osteomyelitis ; Female ; Gallium Radioisotopes - chemistry ; Heterocyclic Compounds, 1-Ring - chemistry ; Humans ; Infection ; Isotope Labeling ; Male ; Oligopeptides - chemical synthesis ; Oligopeptides - chemistry ; Oligopeptides - metabolism ; Osteomyelitis - diagnostic imaging ; Positron emission tomography ; Positron-Emission Tomography - methods ; Rats ; Tissue Distribution ; Vascular adhesion protein-1</subject><ispartof>Nuclear medicine and biology, 2009-08, Vol.36 (6), p.631-641</ispartof><rights>2009 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2159-4e72e3d7dc2d2dc58927fbeaa2568643dd1a53ec54b90e84a9187d37c2fd17233</citedby><cites>FETCH-LOGICAL-c2159-4e72e3d7dc2d2dc58927fbeaa2568643dd1a53ec54b90e84a9187d37c2fd17233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.nucmedbio.2009.04.008$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19647169$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ujula, Tiina</creatorcontrib><creatorcontrib>Salomäki, Satu</creatorcontrib><creatorcontrib>Virsu, Pauliina</creatorcontrib><creatorcontrib>Lankinen, Petteri</creatorcontrib><creatorcontrib>Mäkinen, Tatu J.</creatorcontrib><creatorcontrib>Autio, Anu</creatorcontrib><creatorcontrib>Yegutkin, Gennady G.</creatorcontrib><creatorcontrib>Knuuti, Juhani</creatorcontrib><creatorcontrib>Jalkanen, Sirpa</creatorcontrib><creatorcontrib>Roivainen, Anne</creatorcontrib><title>Synthesis, 68Ga labeling and preliminary evaluation of DOTA peptide binding vascular adhesion protein-1: a potential PET imaging agent for diagnosing osteomyelitis</title><title>Nuclear medicine and biology</title><addtitle>Nucl Med Biol</addtitle><description>Vascular adhesion protein-1 (VAP-1) is an infection/inflammation-inducible endothelial glycoprotein. Based on our previous studies, the most VAP-1-selective peptide (VAP-P1) was 1,4,7,10-tetraazacyclododecane-
N′,
N″,
N‴,
N⁗-tetraacetic acid (DOTA)-conjugated,
68gallium (
68Ga)-labeled (named [
68Ga]DOTAVAP-P1) and evaluated preliminarily.
Targeting was evaluated by using VAP-1-transfected cells. Biodistribution of [
68Ga]DOTAVAP-P1 was studied by positron emission tomography imaging of healthy rats and rats with bone inflammation caused by
Staphylococcus aureus infection. Uptake of [
68Ga]DOTAVAP-P1 in osteomyelitis was compared with negative control peptide and competition with an excess of unlabeled DOTAVAP-P1.
[
68Ga]DOTAVAP-P1 bound more efficiently to VAP-1-transfected cells than to controls. In rats, [
68Ga]DOTAVAP-P1 cleared rapidly from blood circulation, excreted quickly in urine and showed an in vivo half-life of 26±2.3 min. Imaging of osteomyelitis demonstrated modest target-to-background ratio. Studies with the negative control peptide and competitors revealed a significantly lower uptake at the infection site compared to [
68Ga]DOTAVAP-P1.
The results represent a proof-of-concept that infection-induced VAP-1 can be targeted by [
68Ga]DOTA peptide. [
68Ga]DOTAVAP-P1 is just the first candidate peptide and an essential opening for developing VAP-1-specific imaging agents.</description><subject>68Gallium</subject><subject>Amine Oxidase (Copper-Containing) - metabolism</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>DOTA peptide</subject><subject>Experimental osteomyelitis</subject><subject>Female</subject><subject>Gallium Radioisotopes - chemistry</subject><subject>Heterocyclic Compounds, 1-Ring - chemistry</subject><subject>Humans</subject><subject>Infection</subject><subject>Isotope Labeling</subject><subject>Male</subject><subject>Oligopeptides - chemical synthesis</subject><subject>Oligopeptides - chemistry</subject><subject>Oligopeptides - metabolism</subject><subject>Osteomyelitis - diagnostic imaging</subject><subject>Positron emission tomography</subject><subject>Positron-Emission Tomography - methods</subject><subject>Rats</subject><subject>Tissue Distribution</subject><subject>Vascular adhesion protein-1</subject><issn>0969-8051</issn><issn>1872-9614</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2OFCEUhYnROD2jr6Ds3FglUD8U7jrjOJpMMia2a0LBrZZOFZRAddLP44tKTXd06Yqbyzn3cPkQektJSQltPxxKt-gJTG99yQgRJalLQrpnaEM7zgrR0vo52hDRiqIjDb1C1zEeSHbWlLxEV1S0Naet2KDf308u_YRo43vcdvcKj6qH0bo9Vs7gOeR6sk6FE4ajGheVrHfYD_jT426LZ5iTNYB768xqOaqol1EFrMw6Mivn4BNYV9CPWOE51y5ZNeJvdztsJ7V_ytnnJh58wMaqvfNxbfqYwE-nnJ5sfIVeDGqM8Ppy3qAfn-92t1-Kh8f7r7fbh0Iz2oiiBs6gMtxoZpjRTScYH3pQijVt19aVMVQ1Feim7gWBrlYi_5WpuGaDoZxV1Q16d56bX_1rgZjkZKOGcVQO_BIlr6qGNxUlWcnPSh18jAEGOYe8TzhJSuQKSB7kX0ByBSRJLTOg7HxzyVj6fP3PdyGSBduzAPKmRwtBRm3BaTA2gE7SePvfkD9x_6kP</recordid><startdate>200908</startdate><enddate>200908</enddate><creator>Ujula, Tiina</creator><creator>Salomäki, Satu</creator><creator>Virsu, Pauliina</creator><creator>Lankinen, Petteri</creator><creator>Mäkinen, Tatu J.</creator><creator>Autio, Anu</creator><creator>Yegutkin, Gennady G.</creator><creator>Knuuti, Juhani</creator><creator>Jalkanen, Sirpa</creator><creator>Roivainen, Anne</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>200908</creationdate><title>Synthesis, 68Ga labeling and preliminary evaluation of DOTA peptide binding vascular adhesion protein-1: a potential PET imaging agent for diagnosing osteomyelitis</title><author>Ujula, Tiina ; Salomäki, Satu ; Virsu, Pauliina ; Lankinen, Petteri ; Mäkinen, Tatu J. ; Autio, Anu ; Yegutkin, Gennady G. ; Knuuti, Juhani ; Jalkanen, Sirpa ; Roivainen, Anne</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2159-4e72e3d7dc2d2dc58927fbeaa2568643dd1a53ec54b90e84a9187d37c2fd17233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>68Gallium</topic><topic>Amine Oxidase (Copper-Containing) - metabolism</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>DOTA peptide</topic><topic>Experimental osteomyelitis</topic><topic>Female</topic><topic>Gallium Radioisotopes - chemistry</topic><topic>Heterocyclic Compounds, 1-Ring - chemistry</topic><topic>Humans</topic><topic>Infection</topic><topic>Isotope Labeling</topic><topic>Male</topic><topic>Oligopeptides - chemical synthesis</topic><topic>Oligopeptides - chemistry</topic><topic>Oligopeptides - metabolism</topic><topic>Osteomyelitis - diagnostic imaging</topic><topic>Positron emission tomography</topic><topic>Positron-Emission Tomography - methods</topic><topic>Rats</topic><topic>Tissue Distribution</topic><topic>Vascular adhesion protein-1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ujula, Tiina</creatorcontrib><creatorcontrib>Salomäki, Satu</creatorcontrib><creatorcontrib>Virsu, Pauliina</creatorcontrib><creatorcontrib>Lankinen, Petteri</creatorcontrib><creatorcontrib>Mäkinen, Tatu J.</creatorcontrib><creatorcontrib>Autio, Anu</creatorcontrib><creatorcontrib>Yegutkin, Gennady G.</creatorcontrib><creatorcontrib>Knuuti, Juhani</creatorcontrib><creatorcontrib>Jalkanen, Sirpa</creatorcontrib><creatorcontrib>Roivainen, Anne</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Nuclear medicine and biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ujula, Tiina</au><au>Salomäki, Satu</au><au>Virsu, Pauliina</au><au>Lankinen, Petteri</au><au>Mäkinen, Tatu J.</au><au>Autio, Anu</au><au>Yegutkin, Gennady G.</au><au>Knuuti, Juhani</au><au>Jalkanen, Sirpa</au><au>Roivainen, Anne</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis, 68Ga labeling and preliminary evaluation of DOTA peptide binding vascular adhesion protein-1: a potential PET imaging agent for diagnosing osteomyelitis</atitle><jtitle>Nuclear medicine and biology</jtitle><addtitle>Nucl Med Biol</addtitle><date>2009-08</date><risdate>2009</risdate><volume>36</volume><issue>6</issue><spage>631</spage><epage>641</epage><pages>631-641</pages><issn>0969-8051</issn><eissn>1872-9614</eissn><abstract>Vascular adhesion protein-1 (VAP-1) is an infection/inflammation-inducible endothelial glycoprotein. Based on our previous studies, the most VAP-1-selective peptide (VAP-P1) was 1,4,7,10-tetraazacyclododecane-
N′,
N″,
N‴,
N⁗-tetraacetic acid (DOTA)-conjugated,
68gallium (
68Ga)-labeled (named [
68Ga]DOTAVAP-P1) and evaluated preliminarily.
Targeting was evaluated by using VAP-1-transfected cells. Biodistribution of [
68Ga]DOTAVAP-P1 was studied by positron emission tomography imaging of healthy rats and rats with bone inflammation caused by
Staphylococcus aureus infection. Uptake of [
68Ga]DOTAVAP-P1 in osteomyelitis was compared with negative control peptide and competition with an excess of unlabeled DOTAVAP-P1.
[
68Ga]DOTAVAP-P1 bound more efficiently to VAP-1-transfected cells than to controls. In rats, [
68Ga]DOTAVAP-P1 cleared rapidly from blood circulation, excreted quickly in urine and showed an in vivo half-life of 26±2.3 min. Imaging of osteomyelitis demonstrated modest target-to-background ratio. Studies with the negative control peptide and competitors revealed a significantly lower uptake at the infection site compared to [
68Ga]DOTAVAP-P1.
The results represent a proof-of-concept that infection-induced VAP-1 can be targeted by [
68Ga]DOTA peptide. [
68Ga]DOTAVAP-P1 is just the first candidate peptide and an essential opening for developing VAP-1-specific imaging agents.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>19647169</pmid><doi>10.1016/j.nucmedbio.2009.04.008</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Nuclear medicine and biology, 2009-08, Vol.36 (6), p.631-641 |
| issn | 0969-8051 1872-9614 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | 68Gallium Amine Oxidase (Copper-Containing) - metabolism Amino Acid Sequence Animals Cell Adhesion Molecules - metabolism CHO Cells Cricetinae Cricetulus DOTA peptide Experimental osteomyelitis Female Gallium Radioisotopes - chemistry Heterocyclic Compounds, 1-Ring - chemistry Humans Infection Isotope Labeling Male Oligopeptides - chemical synthesis Oligopeptides - chemistry Oligopeptides - metabolism Osteomyelitis - diagnostic imaging Positron emission tomography Positron-Emission Tomography - methods Rats Tissue Distribution Vascular adhesion protein-1 |
| title | Synthesis, 68Ga labeling and preliminary evaluation of DOTA peptide binding vascular adhesion protein-1: a potential PET imaging agent for diagnosing osteomyelitis |
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