Long-Distance Tracing of the Lymphatic System with a Computed Tomography/Fluorescence Dual-Modality Nanoprobe for Surveying Tumor Lymphatic Metastasis
Noninvasive visualization of deep tissue lymphatic metastasis is crucial for diagnosing malignant tumors and predicting prognosis. However, the limited diffusivity and specificity of imaging contrast agents that are transported in lymph vessels (LVs), even for those agents delivered by nanocarriers,...
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| Veröffentlicht in: | Bioconjugate chemistry 2019-04, Vol.30 (4), p.1199-1209 |
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| container_title | Bioconjugate chemistry |
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| creator | Xu, Guoqiang Qian, Yuan Zheng, Hao Qiao, Sha Yan, Dongmei Lu, Lisen Wu, Liujuan Yang, Xiaoquan Luo, Qingming Zhang, Zhihong |
| description | Noninvasive visualization of deep tissue lymphatic metastasis is crucial for diagnosing malignant tumors and predicting prognosis. However, the limited diffusivity and specificity of imaging contrast agents that are transported in lymph vessels (LVs), even for those agents delivered by nanocarriers, make long-distance tracing of the lymphatic system in vivo challenging. Here, we develop a computed tomography (CT)/fluorescence dual-modality phospholipid nanoprobe (PL(I/D)NP) with a negative charge and sub-60 nm size. By using micro-CT, we noninvasively traced the LVs from the subcutaneous injection site in feet to the thoracic ducts with an entire length of ∼68 mm and measured the volume of the lymph nodes (LNs) and their separation distance along the LVs. For diagnostic imaging of tumor lymphatic metastasis, all LNs with metastasis were identified in vivo. Thus, with their long-distance diffusivity, high lymphatic capillary specificity, and quantifiability, the PL(I/D)NPs combined with noninvasive imaging accurately depicted the changes in the lymphatic system under pathologic conditions, especially cancer metastasis, which indicates their high potential for clinical applicability. |
| doi_str_mv | 10.1021/acs.bioconjchem.9b00144 |
| format | Article |
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However, the limited diffusivity and specificity of imaging contrast agents that are transported in lymph vessels (LVs), even for those agents delivered by nanocarriers, make long-distance tracing of the lymphatic system in vivo challenging. Here, we develop a computed tomography (CT)/fluorescence dual-modality phospholipid nanoprobe (PL(I/D)NP) with a negative charge and sub-60 nm size. By using micro-CT, we noninvasively traced the LVs from the subcutaneous injection site in feet to the thoracic ducts with an entire length of ∼68 mm and measured the volume of the lymph nodes (LNs) and their separation distance along the LVs. For diagnostic imaging of tumor lymphatic metastasis, all LNs with metastasis were identified in vivo. Thus, with their long-distance diffusivity, high lymphatic capillary specificity, and quantifiability, the PL(I/D)NPs combined with noninvasive imaging accurately depicted the changes in the lymphatic system under pathologic conditions, especially cancer metastasis, which indicates their high potential for clinical applicability.</description><identifier>ISSN: 1043-1802</identifier><identifier>EISSN: 1520-4812</identifier><identifier>DOI: 10.1021/acs.bioconjchem.9b00144</identifier><identifier>PMID: 30888794</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Computation ; Computed tomography ; Contrast agents ; Contrast Media ; Diagnostic systems ; Diffusivity ; Ducts ; Fluorescence ; Fluorescent Dyes - chemistry ; Humans ; Lymph nodes ; Lymphatic Metastasis - diagnostic imaging ; Lymphatic system ; Lymphatic System - anatomy & histology ; Lymphatic System - diagnostic imaging ; Medical imaging ; Metastases ; Metastasis ; Mice ; Nanoparticles - chemistry ; Phospholipids ; Surveying ; Thorax ; Tumors ; X-Ray Microtomography - methods</subject><ispartof>Bioconjugate chemistry, 2019-04, Vol.30 (4), p.1199-1209</ispartof><rights>Copyright American Chemical Society Apr 17, 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a385t-bf462f1e12631745ea36d1419812f0bb51f58a7b8af6670dbc6990a59e2e4afe3</citedby><cites>FETCH-LOGICAL-a385t-bf462f1e12631745ea36d1419812f0bb51f58a7b8af6670dbc6990a59e2e4afe3</cites><orcidid>0000-0002-3967-7727 ; 0000-0001-5227-8926</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/acs.bioconjchem.9b00144$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00144$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30888794$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Guoqiang</creatorcontrib><creatorcontrib>Qian, Yuan</creatorcontrib><creatorcontrib>Zheng, Hao</creatorcontrib><creatorcontrib>Qiao, Sha</creatorcontrib><creatorcontrib>Yan, Dongmei</creatorcontrib><creatorcontrib>Lu, Lisen</creatorcontrib><creatorcontrib>Wu, Liujuan</creatorcontrib><creatorcontrib>Yang, Xiaoquan</creatorcontrib><creatorcontrib>Luo, Qingming</creatorcontrib><creatorcontrib>Zhang, Zhihong</creatorcontrib><title>Long-Distance Tracing of the Lymphatic System with a Computed Tomography/Fluorescence Dual-Modality Nanoprobe for Surveying Tumor Lymphatic Metastasis</title><title>Bioconjugate chemistry</title><addtitle>Bioconjugate Chem</addtitle><description>Noninvasive visualization of deep tissue lymphatic metastasis is crucial for diagnosing malignant tumors and predicting prognosis. However, the limited diffusivity and specificity of imaging contrast agents that are transported in lymph vessels (LVs), even for those agents delivered by nanocarriers, make long-distance tracing of the lymphatic system in vivo challenging. Here, we develop a computed tomography (CT)/fluorescence dual-modality phospholipid nanoprobe (PL(I/D)NP) with a negative charge and sub-60 nm size. By using micro-CT, we noninvasively traced the LVs from the subcutaneous injection site in feet to the thoracic ducts with an entire length of ∼68 mm and measured the volume of the lymph nodes (LNs) and their separation distance along the LVs. For diagnostic imaging of tumor lymphatic metastasis, all LNs with metastasis were identified in vivo. Thus, with their long-distance diffusivity, high lymphatic capillary specificity, and quantifiability, the PL(I/D)NPs combined with noninvasive imaging accurately depicted the changes in the lymphatic system under pathologic conditions, especially cancer metastasis, which indicates their high potential for clinical applicability.</description><subject>Animals</subject><subject>Computation</subject><subject>Computed tomography</subject><subject>Contrast agents</subject><subject>Contrast Media</subject><subject>Diagnostic systems</subject><subject>Diffusivity</subject><subject>Ducts</subject><subject>Fluorescence</subject><subject>Fluorescent Dyes - chemistry</subject><subject>Humans</subject><subject>Lymph nodes</subject><subject>Lymphatic Metastasis - diagnostic imaging</subject><subject>Lymphatic system</subject><subject>Lymphatic System - anatomy & histology</subject><subject>Lymphatic System - diagnostic imaging</subject><subject>Medical imaging</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Nanoparticles - chemistry</subject><subject>Phospholipids</subject><subject>Surveying</subject><subject>Thorax</subject><subject>Tumors</subject><subject>X-Ray Microtomography - methods</subject><issn>1043-1802</issn><issn>1520-4812</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAUhSMEoqXwCmCJDZtM_ZfEXqIpBaQpLDqso5vkepJREgfbKcqL8Lw4mqEgNqx8LX33nHN1kuQNoxtGObuG2m-qztZ2PNYtDhtdUcqkfJJcsozTVCrGn8aZSpEyRflF8sL7I6VUM8WfJxeCKqUKLS-Tnzs7HtKbzgcYayR7B3U3Hog1JLRIdsswtRC6mtwvPuBAfnShJUC2dpjmgA3Z28EeHEztcn3bz9ahr3HVuZmhT-9sA30XFvIFRjs5WyEx1pH72T3gsrrs5yH-_5jcYYAYxHf-ZfLMQO_x1fm9Sr7dfthvP6W7rx8_b9_vUhAqC2llZM4NQ8ZzwQqZIYi8YZLpeL-hVZUxkykoKgUmzwvaVHWuNYVMI0cJBsVV8u6kG-N9n9GHcujiCX0PI9rZl5xpmSmVCRbRt_-gRzu7MaYrOZdMCKqzlSpOVO2s9w5NObluALeUjJZrdWWsrvyruvJcXdx8fdafqwGbx73fXUVAnIBV4dH7f7K_AHVDrZM</recordid><startdate>20190417</startdate><enddate>20190417</enddate><creator>Xu, Guoqiang</creator><creator>Qian, Yuan</creator><creator>Zheng, Hao</creator><creator>Qiao, Sha</creator><creator>Yan, Dongmei</creator><creator>Lu, Lisen</creator><creator>Wu, Liujuan</creator><creator>Yang, Xiaoquan</creator><creator>Luo, Qingming</creator><creator>Zhang, Zhihong</creator><general>American Chemical Society</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>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3967-7727</orcidid><orcidid>https://orcid.org/0000-0001-5227-8926</orcidid></search><sort><creationdate>20190417</creationdate><title>Long-Distance Tracing of the Lymphatic System with a Computed Tomography/Fluorescence Dual-Modality Nanoprobe for Surveying Tumor Lymphatic Metastasis</title><author>Xu, Guoqiang ; 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| subjects | Animals Computation Computed tomography Contrast agents Contrast Media Diagnostic systems Diffusivity Ducts Fluorescence Fluorescent Dyes - chemistry Humans Lymph nodes Lymphatic Metastasis - diagnostic imaging Lymphatic system Lymphatic System - anatomy & histology Lymphatic System - diagnostic imaging Medical imaging Metastases Metastasis Mice Nanoparticles - chemistry Phospholipids Surveying Thorax Tumors X-Ray Microtomography - methods |
| title | Long-Distance Tracing of the Lymphatic System with a Computed Tomography/Fluorescence Dual-Modality Nanoprobe for Surveying Tumor Lymphatic Metastasis |
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