Targeted Imaging of Lung Cancer with Hyperpolarized 129Xe MRI Using Surface-Modified Iron Oxide Nanoparticles as Molecular Contrast Agents
Hyperpolarized 129Xe (HP 129Xe) MRI enables functional imaging of various lung diseases but has been scarcely applied to lung cancer imaging. The aim of this study is to investigate the feasibility of targeted imaging of lung cancer with HP 129Xe MRI using surface-modified iron oxide nanoparticles (...
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description | Hyperpolarized 129Xe (HP 129Xe) MRI enables functional imaging of various lung diseases but has been scarcely applied to lung cancer imaging. The aim of this study is to investigate the feasibility of targeted imaging of lung cancer with HP 129Xe MRI using surface-modified iron oxide nanoparticles (IONPs) as molecular targeting contrast agents. A mouse model of lung cancer (LC) was induced in nine mice by intra-peritoneal injection of urethane. Three months after the urethane administration, the mice underwent lung imaging with HP 129Xe MRI at baseline (0 h). Subsequently, the LC group was divided into two sub-groups: mice administered with polyethylene glycol-coated IONPs (PEG-IONPs, n = 4) and folate-conjugated dextran-coated IONPs (FA@Dex-IONPs, n = 5). The mice were imaged at 3, 6, and 24 h after the intravenous injection of IONPs. FA@Dex-IONPs mice showed a 25% reduction in average signal intensity at cancer sites at 3 h post injection, and a 24% reduction at 24 h post injection. On the other hand, in PEG-IONPs mice, while a signal reduction of approximately 28% was observed at cancer sites at 3 to 6 h post injection, the signal intensity was unchanged from that of the baseline at 24 h. Proton MRI of LC mice (n = 3) was able to detect cancer five months after urethane administration, i.e., later than HP 129Xe MRI (3 months). Furthermore, a significant decrease in averaged 1H T2 values at cancer sites was observed at only 6 h post injection of FA@Dex-IONPs (p < 0.05). As such, the targeted delivery of IONPs to cancer tissue was successfully imaged with HP 129Xe MRI, and their surface modification with folate likely has a high affinity with LC, which causes overexpression of folate receptors. |
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The aim of this study is to investigate the feasibility of targeted imaging of lung cancer with HP 129Xe MRI using surface-modified iron oxide nanoparticles (IONPs) as molecular targeting contrast agents. A mouse model of lung cancer (LC) was induced in nine mice by intra-peritoneal injection of urethane. Three months after the urethane administration, the mice underwent lung imaging with HP 129Xe MRI at baseline (0 h). Subsequently, the LC group was divided into two sub-groups: mice administered with polyethylene glycol-coated IONPs (PEG-IONPs, n = 4) and folate-conjugated dextran-coated IONPs (FA@Dex-IONPs, n = 5). The mice were imaged at 3, 6, and 24 h after the intravenous injection of IONPs. FA@Dex-IONPs mice showed a 25% reduction in average signal intensity at cancer sites at 3 h post injection, and a 24% reduction at 24 h post injection. On the other hand, in PEG-IONPs mice, while a signal reduction of approximately 28% was observed at cancer sites at 3 to 6 h post injection, the signal intensity was unchanged from that of the baseline at 24 h. Proton MRI of LC mice (n = 3) was able to detect cancer five months after urethane administration, i.e., later than HP 129Xe MRI (3 months). Furthermore, a significant decrease in averaged 1H T2 values at cancer sites was observed at only 6 h post injection of FA@Dex-IONPs (p < 0.05). As such, the targeted delivery of IONPs to cancer tissue was successfully imaged with HP 129Xe MRI, and their surface modification with folate likely has a high affinity with LC, which causes overexpression of folate receptors.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers14246070</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Acids ; Aqueous solutions ; Calibration ; Chronic obstructive pulmonary disease ; Clinical trials ; Coatings ; Contrast media ; Dextran ; Ethyl carbamate ; Folic acid ; Functional magnetic resonance imaging ; Gases ; Injection ; Intravenous administration ; Iron oxides ; Lung cancer ; Lung diseases ; Nanoparticles ; Nitrogen ; Pharmacokinetics ; Polyethylene glycol ; Vitamin B</subject><ispartof>Cancers, 2022-12, Vol.14 (24), p.6070</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c328t-56ef067cb4f0f87928fb9d948c3fe59ad5a3895268c1d3998b86d943f559263d3</citedby><cites>FETCH-LOGICAL-c328t-56ef067cb4f0f87928fb9d948c3fe59ad5a3895268c1d3998b86d943f559263d3</cites><orcidid>0000-0001-8358-394X ; 0000-0001-5702-276X ; 0000-0002-9720-3546</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776850/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776850/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids></links><search><creatorcontrib>Kimura, Atsuomi</creatorcontrib><creatorcontrib>Utsumi, Seiya</creatorcontrib><creatorcontrib>Shimokawa, Akihiro</creatorcontrib><creatorcontrib>Nishimori, Renya</creatorcontrib><creatorcontrib>Hosoi, Rie</creatorcontrib><creatorcontrib>Stewart, Neil J.</creatorcontrib><creatorcontrib>Imai, Hirohiko</creatorcontrib><creatorcontrib>Fujiwara, Hideaki</creatorcontrib><title>Targeted Imaging of Lung Cancer with Hyperpolarized 129Xe MRI Using Surface-Modified Iron Oxide Nanoparticles as Molecular Contrast Agents</title><title>Cancers</title><description>Hyperpolarized 129Xe (HP 129Xe) MRI enables functional imaging of various lung diseases but has been scarcely applied to lung cancer imaging. The aim of this study is to investigate the feasibility of targeted imaging of lung cancer with HP 129Xe MRI using surface-modified iron oxide nanoparticles (IONPs) as molecular targeting contrast agents. A mouse model of lung cancer (LC) was induced in nine mice by intra-peritoneal injection of urethane. Three months after the urethane administration, the mice underwent lung imaging with HP 129Xe MRI at baseline (0 h). Subsequently, the LC group was divided into two sub-groups: mice administered with polyethylene glycol-coated IONPs (PEG-IONPs, n = 4) and folate-conjugated dextran-coated IONPs (FA@Dex-IONPs, n = 5). The mice were imaged at 3, 6, and 24 h after the intravenous injection of IONPs. FA@Dex-IONPs mice showed a 25% reduction in average signal intensity at cancer sites at 3 h post injection, and a 24% reduction at 24 h post injection. On the other hand, in PEG-IONPs mice, while a signal reduction of approximately 28% was observed at cancer sites at 3 to 6 h post injection, the signal intensity was unchanged from that of the baseline at 24 h. Proton MRI of LC mice (n = 3) was able to detect cancer five months after urethane administration, i.e., later than HP 129Xe MRI (3 months). Furthermore, a significant decrease in averaged 1H T2 values at cancer sites was observed at only 6 h post injection of FA@Dex-IONPs (p < 0.05). As such, the targeted delivery of IONPs to cancer tissue was successfully imaged with HP 129Xe MRI, and their surface modification with folate likely has a high affinity with LC, which causes overexpression of folate receptors.</description><subject>Acids</subject><subject>Aqueous solutions</subject><subject>Calibration</subject><subject>Chronic obstructive pulmonary disease</subject><subject>Clinical trials</subject><subject>Coatings</subject><subject>Contrast media</subject><subject>Dextran</subject><subject>Ethyl carbamate</subject><subject>Folic acid</subject><subject>Functional magnetic resonance imaging</subject><subject>Gases</subject><subject>Injection</subject><subject>Intravenous administration</subject><subject>Iron oxides</subject><subject>Lung cancer</subject><subject>Lung diseases</subject><subject>Nanoparticles</subject><subject>Nitrogen</subject><subject>Pharmacokinetics</subject><subject>Polyethylene glycol</subject><subject>Vitamin B</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkU1r3DAQQE1poCHJOVdBL724kSXr61IIS9ss7DbQJJCb0MojR8EruZLdNv0J_dWRm1DazGUG5s1jhqmq0wa_p1ThM2uChZSblrQcC_yqOiRYkJpz1b7-p35TneR8j0tQ2gguDqvf1yb1MEGH1nvT-9Cj6NBmLnn1R4l--OkOXTyMkMY4mOR_FbQh6hbQ9usa3eRl5GpOzliot7Hzzi-uFAO6_Ok7QF9MiKNJk7cDZGQy2sYB7FxUaBXDlEye0HkPYcrH1YEzQ4aT53xU3Xz6eL26qDeXn9er801tKZFTzTg4zIXdtQ47KRSRbqc61UpLHTBlOmaoVIxwaZuOKiV3kpc2dYwpwmlHj6oPT95x3u2hs7BsMegx-b1JDzoar__vBH-n-_hdKyG4ZLgI3j0LUvw2Q5703mcLw2ACxDlrIphsMGlaWdC3L9D7OKdQzlsozouPqUKdPVE2xZwTuL_LNFgv_9Uv_ksfAVd6m08</recordid><startdate>20221209</startdate><enddate>20221209</enddate><creator>Kimura, Atsuomi</creator><creator>Utsumi, Seiya</creator><creator>Shimokawa, Akihiro</creator><creator>Nishimori, Renya</creator><creator>Hosoi, Rie</creator><creator>Stewart, Neil J.</creator><creator>Imai, Hirohiko</creator><creator>Fujiwara, Hideaki</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8358-394X</orcidid><orcidid>https://orcid.org/0000-0001-5702-276X</orcidid><orcidid>https://orcid.org/0000-0002-9720-3546</orcidid></search><sort><creationdate>20221209</creationdate><title>Targeted Imaging of Lung Cancer with Hyperpolarized 129Xe MRI Using Surface-Modified Iron Oxide Nanoparticles as Molecular Contrast Agents</title><author>Kimura, Atsuomi ; 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The aim of this study is to investigate the feasibility of targeted imaging of lung cancer with HP 129Xe MRI using surface-modified iron oxide nanoparticles (IONPs) as molecular targeting contrast agents. A mouse model of lung cancer (LC) was induced in nine mice by intra-peritoneal injection of urethane. Three months after the urethane administration, the mice underwent lung imaging with HP 129Xe MRI at baseline (0 h). Subsequently, the LC group was divided into two sub-groups: mice administered with polyethylene glycol-coated IONPs (PEG-IONPs, n = 4) and folate-conjugated dextran-coated IONPs (FA@Dex-IONPs, n = 5). The mice were imaged at 3, 6, and 24 h after the intravenous injection of IONPs. FA@Dex-IONPs mice showed a 25% reduction in average signal intensity at cancer sites at 3 h post injection, and a 24% reduction at 24 h post injection. On the other hand, in PEG-IONPs mice, while a signal reduction of approximately 28% was observed at cancer sites at 3 to 6 h post injection, the signal intensity was unchanged from that of the baseline at 24 h. Proton MRI of LC mice (n = 3) was able to detect cancer five months after urethane administration, i.e., later than HP 129Xe MRI (3 months). Furthermore, a significant decrease in averaged 1H T2 values at cancer sites was observed at only 6 h post injection of FA@Dex-IONPs (p < 0.05). As such, the targeted delivery of IONPs to cancer tissue was successfully imaged with HP 129Xe MRI, and their surface modification with folate likely has a high affinity with LC, which causes overexpression of folate receptors.</abstract><cop>Basel</cop><pub>MDPI AG</pub><doi>10.3390/cancers14246070</doi><orcidid>https://orcid.org/0000-0001-8358-394X</orcidid><orcidid>https://orcid.org/0000-0001-5702-276X</orcidid><orcidid>https://orcid.org/0000-0002-9720-3546</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Acids Aqueous solutions Calibration Chronic obstructive pulmonary disease Clinical trials Coatings Contrast media Dextran Ethyl carbamate Folic acid Functional magnetic resonance imaging Gases Injection Intravenous administration Iron oxides Lung cancer Lung diseases Nanoparticles Nitrogen Pharmacokinetics Polyethylene glycol Vitamin B |
title | Targeted Imaging of Lung Cancer with Hyperpolarized 129Xe MRI Using Surface-Modified Iron Oxide Nanoparticles as Molecular Contrast Agents |
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