Dendrimer-based MRI contrast agents: the effects of PEGylation on relaxivity and pharmacokinetics
Abstract Polyethylene glycol (PEG) surface modification can make nanomaterials highly hydrophilic, reducing their sequestration in the reticuloendothelial system. In this study, polyamidoamine (PAMAM) dendrimers bearing gadolinium (Gd) chelates were PEGylated with different PEG-chain lengths, and th...
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| Veröffentlicht in: | Nanomedicine 2011-12, Vol.7 (6), p.1001-1008 |
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| creator | Kojima, Chie, PhD Turkbey, Baris, MD Ogawa, Mikako, PhD Bernardo, Marcelino Regino, Celeste A.S., PhD Bryant, L. Henry, PhD Choyke, Peter L., MD Kono, Kenji, PhD Kobayashi, Hisataka, MD, PhD |
| description | Abstract Polyethylene glycol (PEG) surface modification can make nanomaterials highly hydrophilic, reducing their sequestration in the reticuloendothelial system. In this study, polyamidoamine (PAMAM) dendrimers bearing gadolinium (Gd) chelates were PEGylated with different PEG-chain lengths, and the effects on paramagnetic and pharmacokinetic properties were evaluated. Specifically, Gd chelate-bearing PAMAM dendrimers (generations 4 and 5; G4 and G5) were conjugated with two different PEG chains (2 kDa and 5 kDa; 2k and 5k). Long PEG chains (5k) on the smaller (G4) dendrimer resulted in reduced relaxivity compared to non-PEGylated dendrimers, whereas short PEG chains (2k) on a larger (G5) dendrimer produced relaxivities comparable to non-PEGylated G4 dendrimers. The relaxivity of all PEGylated or lysine-conjugated dendrimers increased at higher temperature, whereas that of intact G4 Gd-PAMAM dendrimer decreased. All PEGylated dendrimers had minimal liver and kidney uptake and remained in circulation for at least 1 hour. Thus, surface-PEGylated Gd-PAMAM dendrimers showed decreased plasma clearance and prolonged retention in the blood pool. Shorter PEG, higher generation conjugates led to higher relaxivity. From the Clinical Editor In this study, polyamidoamine dendrimers bearing gadolinium (Gd) chelates were PEGylated with different PEG-chain lengths, and the effects on paramagnetic and pharmacokinetic properties were evaluated. |
| doi_str_mv | 10.1016/j.nano.2011.03.007 |
| format | Article |
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Henry, PhD ; Choyke, Peter L., MD ; Kono, Kenji, PhD ; Kobayashi, Hisataka, MD, PhD</creator><creatorcontrib>Kojima, Chie, PhD ; Turkbey, Baris, MD ; Ogawa, Mikako, PhD ; Bernardo, Marcelino ; Regino, Celeste A.S., PhD ; Bryant, L. Henry, PhD ; Choyke, Peter L., MD ; Kono, Kenji, PhD ; Kobayashi, Hisataka, MD, PhD</creatorcontrib><description>Abstract Polyethylene glycol (PEG) surface modification can make nanomaterials highly hydrophilic, reducing their sequestration in the reticuloendothelial system. In this study, polyamidoamine (PAMAM) dendrimers bearing gadolinium (Gd) chelates were PEGylated with different PEG-chain lengths, and the effects on paramagnetic and pharmacokinetic properties were evaluated. Specifically, Gd chelate-bearing PAMAM dendrimers (generations 4 and 5; G4 and G5) were conjugated with two different PEG chains (2 kDa and 5 kDa; 2k and 5k). Long PEG chains (5k) on the smaller (G4) dendrimer resulted in reduced relaxivity compared to non-PEGylated dendrimers, whereas short PEG chains (2k) on a larger (G5) dendrimer produced relaxivities comparable to non-PEGylated G4 dendrimers. The relaxivity of all PEGylated or lysine-conjugated dendrimers increased at higher temperature, whereas that of intact G4 Gd-PAMAM dendrimer decreased. All PEGylated dendrimers had minimal liver and kidney uptake and remained in circulation for at least 1 hour. Thus, surface-PEGylated Gd-PAMAM dendrimers showed decreased plasma clearance and prolonged retention in the blood pool. Shorter PEG, higher generation conjugates led to higher relaxivity. From the Clinical Editor In this study, polyamidoamine dendrimers bearing gadolinium (Gd) chelates were PEGylated with different PEG-chain lengths, and the effects on paramagnetic and pharmacokinetic properties were evaluated.</description><identifier>ISSN: 1549-9634</identifier><identifier>ISSN: 1549-9642</identifier><identifier>EISSN: 1549-9642</identifier><identifier>DOI: 10.1016/j.nano.2011.03.007</identifier><identifier>PMID: 21515406</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Chelating Agents - chemistry ; Chelating Agents - pharmacokinetics ; Contrast Media - chemistry ; Contrast Media - pharmacokinetics ; Dendrimer ; Dendrimers - chemistry ; Dendrimers - pharmacokinetics ; Gadolinium - chemistry ; Internal Medicine ; Magnetic Resonance Imaging - methods ; Mice ; MRI ; Pharmacokinetics ; Polyethylene glycol ; Polyethylene Glycols - chemistry ; Polyethylene Glycols - pharmacokinetics ; Relaxivity</subject><ispartof>Nanomedicine, 2011-12, Vol.7 (6), p.1001-1008</ispartof><rights>Elsevier Inc.</rights><rights>2011 Elsevier Inc.</rights><rights>Copyright © 2011 Elsevier Inc. All rights reserved.</rights><rights>2011 Elsevier Inc. All rights reserved. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c541t-84382606a6358d3a72961bc9540c67642c9af531be1a82cbe82a43dac8de57223</citedby><cites>FETCH-LOGICAL-c541t-84382606a6358d3a72961bc9540c67642c9af531be1a82cbe82a43dac8de57223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1549963411001043$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21515406$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kojima, Chie, PhD</creatorcontrib><creatorcontrib>Turkbey, Baris, MD</creatorcontrib><creatorcontrib>Ogawa, Mikako, PhD</creatorcontrib><creatorcontrib>Bernardo, Marcelino</creatorcontrib><creatorcontrib>Regino, Celeste A.S., PhD</creatorcontrib><creatorcontrib>Bryant, L. Henry, PhD</creatorcontrib><creatorcontrib>Choyke, Peter L., MD</creatorcontrib><creatorcontrib>Kono, Kenji, PhD</creatorcontrib><creatorcontrib>Kobayashi, Hisataka, MD, PhD</creatorcontrib><title>Dendrimer-based MRI contrast agents: the effects of PEGylation on relaxivity and pharmacokinetics</title><title>Nanomedicine</title><addtitle>Nanomedicine</addtitle><description>Abstract Polyethylene glycol (PEG) surface modification can make nanomaterials highly hydrophilic, reducing their sequestration in the reticuloendothelial system. In this study, polyamidoamine (PAMAM) dendrimers bearing gadolinium (Gd) chelates were PEGylated with different PEG-chain lengths, and the effects on paramagnetic and pharmacokinetic properties were evaluated. Specifically, Gd chelate-bearing PAMAM dendrimers (generations 4 and 5; G4 and G5) were conjugated with two different PEG chains (2 kDa and 5 kDa; 2k and 5k). Long PEG chains (5k) on the smaller (G4) dendrimer resulted in reduced relaxivity compared to non-PEGylated dendrimers, whereas short PEG chains (2k) on a larger (G5) dendrimer produced relaxivities comparable to non-PEGylated G4 dendrimers. The relaxivity of all PEGylated or lysine-conjugated dendrimers increased at higher temperature, whereas that of intact G4 Gd-PAMAM dendrimer decreased. All PEGylated dendrimers had minimal liver and kidney uptake and remained in circulation for at least 1 hour. Thus, surface-PEGylated Gd-PAMAM dendrimers showed decreased plasma clearance and prolonged retention in the blood pool. Shorter PEG, higher generation conjugates led to higher relaxivity. From the Clinical Editor In this study, polyamidoamine dendrimers bearing gadolinium (Gd) chelates were PEGylated with different PEG-chain lengths, and the effects on paramagnetic and pharmacokinetic properties were evaluated.</description><subject>Animals</subject><subject>Chelating Agents - chemistry</subject><subject>Chelating Agents - pharmacokinetics</subject><subject>Contrast Media - chemistry</subject><subject>Contrast Media - pharmacokinetics</subject><subject>Dendrimer</subject><subject>Dendrimers - chemistry</subject><subject>Dendrimers - pharmacokinetics</subject><subject>Gadolinium - chemistry</subject><subject>Internal Medicine</subject><subject>Magnetic Resonance Imaging - methods</subject><subject>Mice</subject><subject>MRI</subject><subject>Pharmacokinetics</subject><subject>Polyethylene glycol</subject><subject>Polyethylene Glycols - chemistry</subject><subject>Polyethylene Glycols - pharmacokinetics</subject><subject>Relaxivity</subject><issn>1549-9634</issn><issn>1549-9642</issn><issn>1549-9642</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk9v1DAQxSMEomXhC3BAuXHaMGMnToJQJVRKqVQE4s_ZmnUmXW-z9tbOrthvj6MtK-AAkiVbmjdP8-bnLHuOUCCgerUqHDlfCEAsQBYA9YPsFKuynbeqFA-Pb1meZE9iXAHIGqB9nJ0IrFIN1GlG79h1wa45zBcUucs_frnKjXdjoDjmdMNujK_zcck59z2bMea-zz9fXO4HGq13eTqBB_phd3bc5-S6fLOksCbjb63j0Zr4NHvU0xD52f09y76_v_h2_mF-_eny6vzt9dxUJY7zppSNUKBIyarpJNWiVbgwbRrTqDrlMS31lcQFIzXCLLgRVMqOTNNxVQshZ9nZwXezXay5MzxlGPQmhaOw156s_rPi7FLf-J2WWLU1YjJ4eW8Q_N2W46jXNhoeBnLst1G3iKgAqvL_SlBVVau0-VkmDkoTfIyB--M8CHqCqFd6gqgniBqkThBT04vfkxxbflFLgjcHAad97iwHHY1lZ7izITHSnbf_9j_7q90M1llDwy3vOa78NrhESqOOQoP-On2j6RchAiCUUv4E3kDDfg</recordid><startdate>20111201</startdate><enddate>20111201</enddate><creator>Kojima, Chie, PhD</creator><creator>Turkbey, Baris, MD</creator><creator>Ogawa, Mikako, PhD</creator><creator>Bernardo, Marcelino</creator><creator>Regino, Celeste A.S., PhD</creator><creator>Bryant, L. Henry, PhD</creator><creator>Choyke, Peter L., MD</creator><creator>Kono, Kenji, PhD</creator><creator>Kobayashi, Hisataka, MD, PhD</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><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20111201</creationdate><title>Dendrimer-based MRI contrast agents: the effects of PEGylation on relaxivity and pharmacokinetics</title><author>Kojima, Chie, PhD ; Turkbey, Baris, MD ; Ogawa, Mikako, PhD ; Bernardo, Marcelino ; Regino, Celeste A.S., PhD ; Bryant, L. Henry, PhD ; Choyke, Peter L., MD ; Kono, Kenji, PhD ; Kobayashi, Hisataka, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c541t-84382606a6358d3a72961bc9540c67642c9af531be1a82cbe82a43dac8de57223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Chelating Agents - chemistry</topic><topic>Chelating Agents - pharmacokinetics</topic><topic>Contrast Media - chemistry</topic><topic>Contrast Media - pharmacokinetics</topic><topic>Dendrimer</topic><topic>Dendrimers - chemistry</topic><topic>Dendrimers - pharmacokinetics</topic><topic>Gadolinium - chemistry</topic><topic>Internal Medicine</topic><topic>Magnetic Resonance Imaging - methods</topic><topic>Mice</topic><topic>MRI</topic><topic>Pharmacokinetics</topic><topic>Polyethylene glycol</topic><topic>Polyethylene Glycols - chemistry</topic><topic>Polyethylene Glycols - pharmacokinetics</topic><topic>Relaxivity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kojima, Chie, PhD</creatorcontrib><creatorcontrib>Turkbey, Baris, MD</creatorcontrib><creatorcontrib>Ogawa, Mikako, PhD</creatorcontrib><creatorcontrib>Bernardo, Marcelino</creatorcontrib><creatorcontrib>Regino, Celeste A.S., PhD</creatorcontrib><creatorcontrib>Bryant, L. 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Henry, PhD</au><au>Choyke, Peter L., MD</au><au>Kono, Kenji, PhD</au><au>Kobayashi, Hisataka, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dendrimer-based MRI contrast agents: the effects of PEGylation on relaxivity and pharmacokinetics</atitle><jtitle>Nanomedicine</jtitle><addtitle>Nanomedicine</addtitle><date>2011-12-01</date><risdate>2011</risdate><volume>7</volume><issue>6</issue><spage>1001</spage><epage>1008</epage><pages>1001-1008</pages><issn>1549-9634</issn><issn>1549-9642</issn><eissn>1549-9642</eissn><abstract>Abstract Polyethylene glycol (PEG) surface modification can make nanomaterials highly hydrophilic, reducing their sequestration in the reticuloendothelial system. In this study, polyamidoamine (PAMAM) dendrimers bearing gadolinium (Gd) chelates were PEGylated with different PEG-chain lengths, and the effects on paramagnetic and pharmacokinetic properties were evaluated. Specifically, Gd chelate-bearing PAMAM dendrimers (generations 4 and 5; G4 and G5) were conjugated with two different PEG chains (2 kDa and 5 kDa; 2k and 5k). Long PEG chains (5k) on the smaller (G4) dendrimer resulted in reduced relaxivity compared to non-PEGylated dendrimers, whereas short PEG chains (2k) on a larger (G5) dendrimer produced relaxivities comparable to non-PEGylated G4 dendrimers. The relaxivity of all PEGylated or lysine-conjugated dendrimers increased at higher temperature, whereas that of intact G4 Gd-PAMAM dendrimer decreased. All PEGylated dendrimers had minimal liver and kidney uptake and remained in circulation for at least 1 hour. Thus, surface-PEGylated Gd-PAMAM dendrimers showed decreased plasma clearance and prolonged retention in the blood pool. Shorter PEG, higher generation conjugates led to higher relaxivity. From the Clinical Editor In this study, polyamidoamine dendrimers bearing gadolinium (Gd) chelates were PEGylated with different PEG-chain lengths, and the effects on paramagnetic and pharmacokinetic properties were evaluated.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21515406</pmid><doi>10.1016/j.nano.2011.03.007</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Chelating Agents - chemistry Chelating Agents - pharmacokinetics Contrast Media - chemistry Contrast Media - pharmacokinetics Dendrimer Dendrimers - chemistry Dendrimers - pharmacokinetics Gadolinium - chemistry Internal Medicine Magnetic Resonance Imaging - methods Mice MRI Pharmacokinetics Polyethylene glycol Polyethylene Glycols - chemistry Polyethylene Glycols - pharmacokinetics Relaxivity |
| title | Dendrimer-based MRI contrast agents: the effects of PEGylation on relaxivity and pharmacokinetics |
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