HAP-Multitag, a PET and Positive MRI Contrast Nanotracer for the Longitudinal Characterization of Vascular Calcifications in Atherosclerosis
Vascular microcalcifications are associated with atherosclerosis plaque instability and, therefore, to increased mortality. Because of this key role, several imaging probes have been developed for their in vivo identification. Among them, [18F]FNa is the gold standard, showing a large uptake in the...
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| Veröffentlicht in: | ACS applied materials & interfaces 2021-09, Vol.13 (38), p.45279-45290 |
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| creator | Pellico, Juan Fernández-Barahona, Irene Ruiz-Cabello, Jesús Gutiérrez, Lucía Muñoz-Hernando, María Sánchez-Guisado, María J Aiestaran-Zelaia, Irati Martínez-Parra, Lydia Rodríguez, Ignacio Bentzon, Jacob Herranz, Fernando |
| description | Vascular microcalcifications are associated with atherosclerosis plaque instability and, therefore, to increased mortality. Because of this key role, several imaging probes have been developed for their in vivo identification. Among them, [18F]FNa is the gold standard, showing a large uptake in the whole skeleton by positron emission tomography. Here, we push the field toward the combined anatomical and functional early characterization of atherosclerosis. For this, we have developed hydroxyapatite (HAP)-multitag, a bisphosphonate-functionalized 68Ga core-doped magnetic nanoparticle showing high affinity toward most common calcium salts present in microcalcifications, particularly HAP. We characterized this interaction in vitro and in vivo, showing a massive uptake in the atherosclerotic lesion identified by positron emission tomography (PET) and positive contrast magnetic resonance imaging (MRI). In addition, this accumulation was found to be dependent on the calcification progression, with a maximum uptake in the microcalcification stage. These results confirmed the ability of HAP-multitag to identify vascular calcifications by PET/(T1)MRI during the vulnerable stages of the plaque progression. |
| doi_str_mv | 10.1021/acsami.1c13417 |
| format | Article |
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Because of this key role, several imaging probes have been developed for their in vivo identification. Among them, [18F]FNa is the gold standard, showing a large uptake in the whole skeleton by positron emission tomography. Here, we push the field toward the combined anatomical and functional early characterization of atherosclerosis. For this, we have developed hydroxyapatite (HAP)-multitag, a bisphosphonate-functionalized 68Ga core-doped magnetic nanoparticle showing high affinity toward most common calcium salts present in microcalcifications, particularly HAP. We characterized this interaction in vitro and in vivo, showing a massive uptake in the atherosclerotic lesion identified by positron emission tomography (PET) and positive contrast magnetic resonance imaging (MRI). In addition, this accumulation was found to be dependent on the calcification progression, with a maximum uptake in the microcalcification stage. These results confirmed the ability of HAP-multitag to identify vascular calcifications by PET/(T1)MRI during the vulnerable stages of the plaque progression.</description><identifier>ISSN: 1944-8244</identifier><identifier>EISSN: 1944-8252</identifier><identifier>DOI: 10.1021/acsami.1c13417</identifier><identifier>PMID: 34529427</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Alendronate - chemistry ; Animals ; Aorta - pathology ; Atherosclerosis - complications ; Atherosclerosis - diagnosis ; Atherosclerosis - pathology ; Biological and Medical Applications of Materials and Interfaces ; Contrast Media - chemistry ; Durapatite - chemistry ; Gallium Radioisotopes - chemistry ; Magnetic Iron Oxide Nanoparticles - chemistry ; Magnetic Resonance Imaging ; Mice ; Multimodal Imaging ; Plaque, Atherosclerotic - diagnosis ; Plaque, Atherosclerotic - etiology ; Plaque, Atherosclerotic - pathology ; Positron-Emission Tomography ; Vascular Calcification - diagnostic imaging ; Vascular Calcification - etiology ; Vascular Calcification - pathology</subject><ispartof>ACS applied materials & interfaces, 2021-09, Vol.13 (38), p.45279-45290</ispartof><rights>2021 The Authors. Published by American Chemical Society</rights><rights>2021 The Authors. Published by American Chemical Society 2021 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a425t-c335c0672a41cbde87d830233243467fce45bf2a190ca9f96b82601056d920563</citedby><cites>FETCH-LOGICAL-a425t-c335c0672a41cbde87d830233243467fce45bf2a190ca9f96b82601056d920563</cites><orcidid>0000-0003-2366-3598 ; 0000-0001-8681-5056 ; 0000-0002-3743-0050 ; 0000-0003-2787-8641</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acsami.1c13417$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acsami.1c13417$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>230,314,780,784,885,2763,27075,27923,27924,56737,56787</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34529427$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pellico, Juan</creatorcontrib><creatorcontrib>Fernández-Barahona, Irene</creatorcontrib><creatorcontrib>Ruiz-Cabello, Jesús</creatorcontrib><creatorcontrib>Gutiérrez, Lucía</creatorcontrib><creatorcontrib>Muñoz-Hernando, María</creatorcontrib><creatorcontrib>Sánchez-Guisado, María J</creatorcontrib><creatorcontrib>Aiestaran-Zelaia, Irati</creatorcontrib><creatorcontrib>Martínez-Parra, Lydia</creatorcontrib><creatorcontrib>Rodríguez, Ignacio</creatorcontrib><creatorcontrib>Bentzon, Jacob</creatorcontrib><creatorcontrib>Herranz, Fernando</creatorcontrib><title>HAP-Multitag, a PET and Positive MRI Contrast Nanotracer for the Longitudinal Characterization of Vascular Calcifications in Atherosclerosis</title><title>ACS applied materials & interfaces</title><addtitle>ACS Appl. Mater. Interfaces</addtitle><description>Vascular microcalcifications are associated with atherosclerosis plaque instability and, therefore, to increased mortality. Because of this key role, several imaging probes have been developed for their in vivo identification. Among them, [18F]FNa is the gold standard, showing a large uptake in the whole skeleton by positron emission tomography. Here, we push the field toward the combined anatomical and functional early characterization of atherosclerosis. For this, we have developed hydroxyapatite (HAP)-multitag, a bisphosphonate-functionalized 68Ga core-doped magnetic nanoparticle showing high affinity toward most common calcium salts present in microcalcifications, particularly HAP. We characterized this interaction in vitro and in vivo, showing a massive uptake in the atherosclerotic lesion identified by positron emission tomography (PET) and positive contrast magnetic resonance imaging (MRI). 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Fernández-Barahona, Irene ; Ruiz-Cabello, Jesús ; Gutiérrez, Lucía ; Muñoz-Hernando, María ; Sánchez-Guisado, María J ; Aiestaran-Zelaia, Irati ; Martínez-Parra, Lydia ; Rodríguez, Ignacio ; Bentzon, Jacob ; Herranz, Fernando</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a425t-c335c0672a41cbde87d830233243467fce45bf2a190ca9f96b82601056d920563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Alendronate - chemistry</topic><topic>Animals</topic><topic>Aorta - pathology</topic><topic>Atherosclerosis - complications</topic><topic>Atherosclerosis - diagnosis</topic><topic>Atherosclerosis - pathology</topic><topic>Biological and Medical Applications of Materials and Interfaces</topic><topic>Contrast Media - chemistry</topic><topic>Durapatite - chemistry</topic><topic>Gallium Radioisotopes - chemistry</topic><topic>Magnetic Iron Oxide Nanoparticles - chemistry</topic><topic>Magnetic Resonance Imaging</topic><topic>Mice</topic><topic>Multimodal Imaging</topic><topic>Plaque, Atherosclerotic - diagnosis</topic><topic>Plaque, Atherosclerotic - etiology</topic><topic>Plaque, Atherosclerotic - pathology</topic><topic>Positron-Emission Tomography</topic><topic>Vascular Calcification - diagnostic imaging</topic><topic>Vascular Calcification - etiology</topic><topic>Vascular Calcification - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pellico, Juan</creatorcontrib><creatorcontrib>Fernández-Barahona, Irene</creatorcontrib><creatorcontrib>Ruiz-Cabello, Jesús</creatorcontrib><creatorcontrib>Gutiérrez, Lucía</creatorcontrib><creatorcontrib>Muñoz-Hernando, María</creatorcontrib><creatorcontrib>Sánchez-Guisado, María J</creatorcontrib><creatorcontrib>Aiestaran-Zelaia, Irati</creatorcontrib><creatorcontrib>Martínez-Parra, Lydia</creatorcontrib><creatorcontrib>Rodríguez, Ignacio</creatorcontrib><creatorcontrib>Bentzon, Jacob</creatorcontrib><creatorcontrib>Herranz, Fernando</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>ACS applied materials & interfaces</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pellico, Juan</au><au>Fernández-Barahona, Irene</au><au>Ruiz-Cabello, Jesús</au><au>Gutiérrez, Lucía</au><au>Muñoz-Hernando, María</au><au>Sánchez-Guisado, María J</au><au>Aiestaran-Zelaia, Irati</au><au>Martínez-Parra, Lydia</au><au>Rodríguez, Ignacio</au><au>Bentzon, Jacob</au><au>Herranz, Fernando</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HAP-Multitag, a PET and Positive MRI Contrast Nanotracer for the Longitudinal Characterization of Vascular Calcifications in Atherosclerosis</atitle><jtitle>ACS applied materials & interfaces</jtitle><addtitle>ACS Appl. Mater. Interfaces</addtitle><date>2021-09-29</date><risdate>2021</risdate><volume>13</volume><issue>38</issue><spage>45279</spage><epage>45290</epage><pages>45279-45290</pages><issn>1944-8244</issn><eissn>1944-8252</eissn><abstract>Vascular microcalcifications are associated with atherosclerosis plaque instability and, therefore, to increased mortality. Because of this key role, several imaging probes have been developed for their in vivo identification. Among them, [18F]FNa is the gold standard, showing a large uptake in the whole skeleton by positron emission tomography. Here, we push the field toward the combined anatomical and functional early characterization of atherosclerosis. For this, we have developed hydroxyapatite (HAP)-multitag, a bisphosphonate-functionalized 68Ga core-doped magnetic nanoparticle showing high affinity toward most common calcium salts present in microcalcifications, particularly HAP. We characterized this interaction in vitro and in vivo, showing a massive uptake in the atherosclerotic lesion identified by positron emission tomography (PET) and positive contrast magnetic resonance imaging (MRI). In addition, this accumulation was found to be dependent on the calcification progression, with a maximum uptake in the microcalcification stage. These results confirmed the ability of HAP-multitag to identify vascular calcifications by PET/(T1)MRI during the vulnerable stages of the plaque progression.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>34529427</pmid><doi>10.1021/acsami.1c13417</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-2366-3598</orcidid><orcidid>https://orcid.org/0000-0001-8681-5056</orcidid><orcidid>https://orcid.org/0000-0002-3743-0050</orcidid><orcidid>https://orcid.org/0000-0003-2787-8641</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; ACS Publications |
| subjects | Alendronate - chemistry Animals Aorta - pathology Atherosclerosis - complications Atherosclerosis - diagnosis Atherosclerosis - pathology Biological and Medical Applications of Materials and Interfaces Contrast Media - chemistry Durapatite - chemistry Gallium Radioisotopes - chemistry Magnetic Iron Oxide Nanoparticles - chemistry Magnetic Resonance Imaging Mice Multimodal Imaging Plaque, Atherosclerotic - diagnosis Plaque, Atherosclerotic - etiology Plaque, Atherosclerotic - pathology Positron-Emission Tomography Vascular Calcification - diagnostic imaging Vascular Calcification - etiology Vascular Calcification - pathology |
| title | HAP-Multitag, a PET and Positive MRI Contrast Nanotracer for the Longitudinal Characterization of Vascular Calcifications in Atherosclerosis |
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