Design and Evaluation of Rhein-Based MRI Contrast Agents for Visualization of Tumor Necrosis Induced by Combretastatin A-4 Disodium Phosphate
Purpose Visualization of tumor necrosis can determine tumor response to therapy. Our previous study showed that the rhein-based magnetic resonance imaging (MRI) contrast agent with alkane linker (GdL 2 ) could clearly image tumor necrosis. However, its water solubility and cell safety needed to be i...
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| Veröffentlicht in: | Molecular imaging and biology 2021-04, Vol.23 (2), p.220-229 |
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| creator | Zhang, Libang Zhang, Dongjian Gao, Meng Jin, Qiaomei Jiang, Cuihua Wu, Tianze Feng, Yuanbo Ni, Yicheng Yin, Zhiqi Zhang, Jian |
| description | Purpose
Visualization of tumor necrosis can determine tumor response to therapy. Our previous study showed that the rhein-based magnetic resonance imaging (MRI) contrast agent with alkane linker (GdL
2
) could clearly image tumor necrosis. However, its water solubility and cell safety needed to be improved. Herein, three rhein-based MRI agents with ether or lysine linkers were designed.
Procedures
Three rhein-based MRI agents were synthesized with a tetracarbon ether (GdP1), a hexacarbon ether (GdP2), and a lysine (GdP3) linker, respectively. Their octanol-water partition coefficients (log
P
) and cytotoxicity were determined. Necrosis avidity of the leading agent was explored on HepG2 cells and ischemia reperfusion-induced liver necrosis (IRLN) rats by MRI. The effect of visualization of tumor necrosis was tested on nude mice with W256 tumor treated by combretastatin-A4 phosphate (CA4P). DNA binding assays were applied to evaluate the possible necrosis-avidity mechanism of the leading agent.
Results
The log
P
of three agents (− 1.66 ± 0.09, − 1.74 ± 0.01, − 1.95 ± 0.01) decreased when compared with GdL
2
, indicating higher water solubility. GdP1 not only presented lower cytotoxicity and good necrotic affinity
in vitro
and
in vivo
, but also can be fast excreted by renal. According to MRI results of tumor, distinct visualization of tumor necrosis can be discernible from 3 to 4.5 h post-injection of GdP1. In DNA-binding assays, the fluorescence quenching constant
K
SV
(1.00 × 10
4
M
−1
) and the ultraviolet binding constant
K
b
(1.11 × 10
4
M
−1
) suggested that GdP1 may bind to DNA through intercalation.
Conclusion
GdP1 may serve as a potential candidate for early evaluation of tumor response to CA4P treatment. |
| doi_str_mv | 10.1007/s11307-020-01551-3 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2450673268</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2450673268</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-e8f3ae61633ff1e4f0de1555d63c0955b1c6a6d9d87eefa6eccb7d4fe7b54e123</originalsourceid><addsrcrecordid>eNp9kctuFDEQRVuIiITAD7BAltiwceJH2-5ZDpNARgoPRYGt5W6XZxx12xO7jRT-gX_GYUKQWLByyXXutatu07yi5IQSok4zpZwoTBjBhApBMX_SHNFOEswIYU9rLbjEVHJ22DzP-YYQqijjz5pDzknbMUWOmp9nkP0mIBMsOv9uxmJmHwOKDl1twQf8zmSw6OPVGq1imJPJM1puIMwZuZjQN5-LGf2PR9F1mer1JxhSzD6jdbBlqPr-rsqnPsFcDSoc0BK36MznaH2Z0JdtzLutmeFFc-DMmOHlw3ncfH1_fr26wJefP6xXy0s8cCVmDJ3jBmSdjDtHoXXEQl2AsJIPZCFETwdppF3YTgE4I2EYemVbB6oXLdQVHDdv9767FG8L5FlPPg8wjiZALFmzVhCpOJNdRd_8g97EkkL9XaUWvBNMCloptqfuB88JnN4lP5l0pynR92HpfVi6hqV_h6V5Fb1-sC79BPZR8iedCvA9kGsrbCD9ffs_tr8Au2qgbg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2493852651</pqid></control><display><type>article</type><title>Design and Evaluation of Rhein-Based MRI Contrast Agents for Visualization of Tumor Necrosis Induced by Combretastatin A-4 Disodium Phosphate</title><source>SpringerLink Journals - AutoHoldings</source><creator>Zhang, Libang ; Zhang, Dongjian ; Gao, Meng ; Jin, Qiaomei ; Jiang, Cuihua ; Wu, Tianze ; Feng, Yuanbo ; Ni, Yicheng ; Yin, Zhiqi ; Zhang, Jian</creator><creatorcontrib>Zhang, Libang ; Zhang, Dongjian ; Gao, Meng ; Jin, Qiaomei ; Jiang, Cuihua ; Wu, Tianze ; Feng, Yuanbo ; Ni, Yicheng ; Yin, Zhiqi ; Zhang, Jian</creatorcontrib><description>Purpose
Visualization of tumor necrosis can determine tumor response to therapy. Our previous study showed that the rhein-based magnetic resonance imaging (MRI) contrast agent with alkane linker (GdL
2
) could clearly image tumor necrosis. However, its water solubility and cell safety needed to be improved. Herein, three rhein-based MRI agents with ether or lysine linkers were designed.
Procedures
Three rhein-based MRI agents were synthesized with a tetracarbon ether (GdP1), a hexacarbon ether (GdP2), and a lysine (GdP3) linker, respectively. Their octanol-water partition coefficients (log
P
) and cytotoxicity were determined. Necrosis avidity of the leading agent was explored on HepG2 cells and ischemia reperfusion-induced liver necrosis (IRLN) rats by MRI. The effect of visualization of tumor necrosis was tested on nude mice with W256 tumor treated by combretastatin-A4 phosphate (CA4P). DNA binding assays were applied to evaluate the possible necrosis-avidity mechanism of the leading agent.
Results
The log
P
of three agents (− 1.66 ± 0.09, − 1.74 ± 0.01, − 1.95 ± 0.01) decreased when compared with GdL
2
, indicating higher water solubility. GdP1 not only presented lower cytotoxicity and good necrotic affinity
in vitro
and
in vivo
, but also can be fast excreted by renal. According to MRI results of tumor, distinct visualization of tumor necrosis can be discernible from 3 to 4.5 h post-injection of GdP1. In DNA-binding assays, the fluorescence quenching constant
K
SV
(1.00 × 10
4
M
−1
) and the ultraviolet binding constant
K
b
(1.11 × 10
4
M
−1
) suggested that GdP1 may bind to DNA through intercalation.
Conclusion
GdP1 may serve as a potential candidate for early evaluation of tumor response to CA4P treatment.</description><identifier>ISSN: 1536-1632</identifier><identifier>EISSN: 1860-2002</identifier><identifier>DOI: 10.1007/s11307-020-01551-3</identifier><identifier>PMID: 33048270</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Alkanes ; Avidity ; Binding ; Biocompatibility ; Contrast agents ; Contrast media ; Cytotoxicity ; Deoxyribonucleic acid ; DNA ; Fluorescence ; Image contrast ; Imaging ; Ischemia ; Lysine ; Magnetic resonance imaging ; Medicine ; Medicine & Public Health ; Necrosis ; Octanol-water partition coefficients ; Radiology ; Reperfusion ; Research Article ; Sodium hydrogen phosphate ; Sodium phosphate ; Solubility ; Toxicity ; Tumors ; Visualization</subject><ispartof>Molecular imaging and biology, 2021-04, Vol.23 (2), p.220-229</ispartof><rights>World Molecular Imaging Society 2020</rights><rights>World Molecular Imaging Society 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-e8f3ae61633ff1e4f0de1555d63c0955b1c6a6d9d87eefa6eccb7d4fe7b54e123</citedby><cites>FETCH-LOGICAL-c375t-e8f3ae61633ff1e4f0de1555d63c0955b1c6a6d9d87eefa6eccb7d4fe7b54e123</cites><orcidid>0000-0002-8402-9753</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11307-020-01551-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11307-020-01551-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33048270$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Libang</creatorcontrib><creatorcontrib>Zhang, Dongjian</creatorcontrib><creatorcontrib>Gao, Meng</creatorcontrib><creatorcontrib>Jin, Qiaomei</creatorcontrib><creatorcontrib>Jiang, Cuihua</creatorcontrib><creatorcontrib>Wu, Tianze</creatorcontrib><creatorcontrib>Feng, Yuanbo</creatorcontrib><creatorcontrib>Ni, Yicheng</creatorcontrib><creatorcontrib>Yin, Zhiqi</creatorcontrib><creatorcontrib>Zhang, Jian</creatorcontrib><title>Design and Evaluation of Rhein-Based MRI Contrast Agents for Visualization of Tumor Necrosis Induced by Combretastatin A-4 Disodium Phosphate</title><title>Molecular imaging and biology</title><addtitle>Mol Imaging Biol</addtitle><addtitle>Mol Imaging Biol</addtitle><description>Purpose
Visualization of tumor necrosis can determine tumor response to therapy. Our previous study showed that the rhein-based magnetic resonance imaging (MRI) contrast agent with alkane linker (GdL
2
) could clearly image tumor necrosis. However, its water solubility and cell safety needed to be improved. Herein, three rhein-based MRI agents with ether or lysine linkers were designed.
Procedures
Three rhein-based MRI agents were synthesized with a tetracarbon ether (GdP1), a hexacarbon ether (GdP2), and a lysine (GdP3) linker, respectively. Their octanol-water partition coefficients (log
P
) and cytotoxicity were determined. Necrosis avidity of the leading agent was explored on HepG2 cells and ischemia reperfusion-induced liver necrosis (IRLN) rats by MRI. The effect of visualization of tumor necrosis was tested on nude mice with W256 tumor treated by combretastatin-A4 phosphate (CA4P). DNA binding assays were applied to evaluate the possible necrosis-avidity mechanism of the leading agent.
Results
The log
P
of three agents (− 1.66 ± 0.09, − 1.74 ± 0.01, − 1.95 ± 0.01) decreased when compared with GdL
2
, indicating higher water solubility. GdP1 not only presented lower cytotoxicity and good necrotic affinity
in vitro
and
in vivo
, but also can be fast excreted by renal. According to MRI results of tumor, distinct visualization of tumor necrosis can be discernible from 3 to 4.5 h post-injection of GdP1. In DNA-binding assays, the fluorescence quenching constant
K
SV
(1.00 × 10
4
M
−1
) and the ultraviolet binding constant
K
b
(1.11 × 10
4
M
−1
) suggested that GdP1 may bind to DNA through intercalation.
Conclusion
GdP1 may serve as a potential candidate for early evaluation of tumor response to CA4P treatment.</description><subject>Alkanes</subject><subject>Avidity</subject><subject>Binding</subject><subject>Biocompatibility</subject><subject>Contrast agents</subject><subject>Contrast media</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Fluorescence</subject><subject>Image contrast</subject><subject>Imaging</subject><subject>Ischemia</subject><subject>Lysine</subject><subject>Magnetic resonance imaging</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Necrosis</subject><subject>Octanol-water partition coefficients</subject><subject>Radiology</subject><subject>Reperfusion</subject><subject>Research Article</subject><subject>Sodium hydrogen phosphate</subject><subject>Sodium phosphate</subject><subject>Solubility</subject><subject>Toxicity</subject><subject>Tumors</subject><subject>Visualization</subject><issn>1536-1632</issn><issn>1860-2002</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kctuFDEQRVuIiITAD7BAltiwceJH2-5ZDpNARgoPRYGt5W6XZxx12xO7jRT-gX_GYUKQWLByyXXutatu07yi5IQSok4zpZwoTBjBhApBMX_SHNFOEswIYU9rLbjEVHJ22DzP-YYQqijjz5pDzknbMUWOmp9nkP0mIBMsOv9uxmJmHwOKDl1twQf8zmSw6OPVGq1imJPJM1puIMwZuZjQN5-LGf2PR9F1mer1JxhSzD6jdbBlqPr-rsqnPsFcDSoc0BK36MznaH2Z0JdtzLutmeFFc-DMmOHlw3ncfH1_fr26wJefP6xXy0s8cCVmDJ3jBmSdjDtHoXXEQl2AsJIPZCFETwdppF3YTgE4I2EYemVbB6oXLdQVHDdv9767FG8L5FlPPg8wjiZALFmzVhCpOJNdRd_8g97EkkL9XaUWvBNMCloptqfuB88JnN4lP5l0pynR92HpfVi6hqV_h6V5Fb1-sC79BPZR8iedCvA9kGsrbCD9ffs_tr8Au2qgbg</recordid><startdate>20210401</startdate><enddate>20210401</enddate><creator>Zhang, Libang</creator><creator>Zhang, Dongjian</creator><creator>Gao, Meng</creator><creator>Jin, Qiaomei</creator><creator>Jiang, Cuihua</creator><creator>Wu, Tianze</creator><creator>Feng, Yuanbo</creator><creator>Ni, Yicheng</creator><creator>Yin, Zhiqi</creator><creator>Zhang, Jian</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8402-9753</orcidid></search><sort><creationdate>20210401</creationdate><title>Design and Evaluation of Rhein-Based MRI Contrast Agents for Visualization of Tumor Necrosis Induced by Combretastatin A-4 Disodium Phosphate</title><author>Zhang, Libang ; Zhang, Dongjian ; Gao, Meng ; Jin, Qiaomei ; Jiang, Cuihua ; Wu, Tianze ; Feng, Yuanbo ; Ni, Yicheng ; Yin, Zhiqi ; Zhang, Jian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-e8f3ae61633ff1e4f0de1555d63c0955b1c6a6d9d87eefa6eccb7d4fe7b54e123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Alkanes</topic><topic>Avidity</topic><topic>Binding</topic><topic>Biocompatibility</topic><topic>Contrast agents</topic><topic>Contrast media</topic><topic>Cytotoxicity</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Fluorescence</topic><topic>Image contrast</topic><topic>Imaging</topic><topic>Ischemia</topic><topic>Lysine</topic><topic>Magnetic resonance imaging</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Necrosis</topic><topic>Octanol-water partition coefficients</topic><topic>Radiology</topic><topic>Reperfusion</topic><topic>Research Article</topic><topic>Sodium hydrogen phosphate</topic><topic>Sodium phosphate</topic><topic>Solubility</topic><topic>Toxicity</topic><topic>Tumors</topic><topic>Visualization</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Libang</creatorcontrib><creatorcontrib>Zhang, Dongjian</creatorcontrib><creatorcontrib>Gao, Meng</creatorcontrib><creatorcontrib>Jin, Qiaomei</creatorcontrib><creatorcontrib>Jiang, Cuihua</creatorcontrib><creatorcontrib>Wu, Tianze</creatorcontrib><creatorcontrib>Feng, Yuanbo</creatorcontrib><creatorcontrib>Ni, Yicheng</creatorcontrib><creatorcontrib>Yin, Zhiqi</creatorcontrib><creatorcontrib>Zhang, Jian</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular imaging and biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Libang</au><au>Zhang, Dongjian</au><au>Gao, Meng</au><au>Jin, Qiaomei</au><au>Jiang, Cuihua</au><au>Wu, Tianze</au><au>Feng, Yuanbo</au><au>Ni, Yicheng</au><au>Yin, Zhiqi</au><au>Zhang, Jian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design and Evaluation of Rhein-Based MRI Contrast Agents for Visualization of Tumor Necrosis Induced by Combretastatin A-4 Disodium Phosphate</atitle><jtitle>Molecular imaging and biology</jtitle><stitle>Mol Imaging Biol</stitle><addtitle>Mol Imaging Biol</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>23</volume><issue>2</issue><spage>220</spage><epage>229</epage><pages>220-229</pages><issn>1536-1632</issn><eissn>1860-2002</eissn><abstract>Purpose
Visualization of tumor necrosis can determine tumor response to therapy. Our previous study showed that the rhein-based magnetic resonance imaging (MRI) contrast agent with alkane linker (GdL
2
) could clearly image tumor necrosis. However, its water solubility and cell safety needed to be improved. Herein, three rhein-based MRI agents with ether or lysine linkers were designed.
Procedures
Three rhein-based MRI agents were synthesized with a tetracarbon ether (GdP1), a hexacarbon ether (GdP2), and a lysine (GdP3) linker, respectively. Their octanol-water partition coefficients (log
P
) and cytotoxicity were determined. Necrosis avidity of the leading agent was explored on HepG2 cells and ischemia reperfusion-induced liver necrosis (IRLN) rats by MRI. The effect of visualization of tumor necrosis was tested on nude mice with W256 tumor treated by combretastatin-A4 phosphate (CA4P). DNA binding assays were applied to evaluate the possible necrosis-avidity mechanism of the leading agent.
Results
The log
P
of three agents (− 1.66 ± 0.09, − 1.74 ± 0.01, − 1.95 ± 0.01) decreased when compared with GdL
2
, indicating higher water solubility. GdP1 not only presented lower cytotoxicity and good necrotic affinity
in vitro
and
in vivo
, but also can be fast excreted by renal. According to MRI results of tumor, distinct visualization of tumor necrosis can be discernible from 3 to 4.5 h post-injection of GdP1. In DNA-binding assays, the fluorescence quenching constant
K
SV
(1.00 × 10
4
M
−1
) and the ultraviolet binding constant
K
b
(1.11 × 10
4
M
−1
) suggested that GdP1 may bind to DNA through intercalation.
Conclusion
GdP1 may serve as a potential candidate for early evaluation of tumor response to CA4P treatment.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>33048270</pmid><doi>10.1007/s11307-020-01551-3</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-8402-9753</orcidid></addata></record> |
| fulltext | fulltext |
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| ispartof | Molecular imaging and biology, 2021-04, Vol.23 (2), p.220-229 |
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| source | SpringerLink Journals - AutoHoldings |
| subjects | Alkanes Avidity Binding Biocompatibility Contrast agents Contrast media Cytotoxicity Deoxyribonucleic acid DNA Fluorescence Image contrast Imaging Ischemia Lysine Magnetic resonance imaging Medicine Medicine & Public Health Necrosis Octanol-water partition coefficients Radiology Reperfusion Research Article Sodium hydrogen phosphate Sodium phosphate Solubility Toxicity Tumors Visualization |
| title | Design and Evaluation of Rhein-Based MRI Contrast Agents for Visualization of Tumor Necrosis Induced by Combretastatin A-4 Disodium Phosphate |
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