Application of arsenazo III in the preparation and characterization of an albumin-linked, gadolinium-based macromolecular magnetic resonance contrast agent
A macromolecular magnetic resonance contrast agent (MMCA) was prepared by linking bovine serum albumin (BSA) to gadolinium (Gd) via a chelating agent, diethylenetriaminepentaacetic acid (DTPA). Colorimetric testing with 2,7-bis( o-arsenophenylazo)-1,8-dihydroxynaphthalene-3,6-disulfonic acid (arsena...
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creator | Nagaraja, Tavarekere N. Croxen, Richard L. Panda, Swayamprava Knight, Robert A. Keenan, Kelly A. Brown, Stephen L. Fenstermacher, Joseph D. Ewing, James R. |
description | A macromolecular magnetic resonance contrast agent (MMCA) was prepared by linking bovine serum albumin (BSA) to gadolinium (Gd) via a chelating agent, diethylenetriaminepentaacetic acid (DTPA). Colorimetric testing with 2,7-bis(
o-arsenophenylazo)-1,8-dihydroxynaphthalene-3,6-disulfonic acid (arsenazo III) was performed to check for the appearance of free gadolinium during preparation and to quantify the Gd content in the final product. The complex was purified by dialysis, concentrated by lyophilyzation and characterized by magnetic resonance (MR) proton relaxation times. The resultant product had a molecular weight of about 90
kDa, Gd:BSA ratio of 14:1, and
T
1 and
T
2 relaxation times of 128.3 and 48.9
ms, respectively, at a field strength of 7
Tesla (T) and at 20% concentration. Contrast enhancement of Gadomer-17 (a dendritic MMCA) and Gd-linked to BSA (Gd–BSA) was sequentially evaluated in a rat brain gliosarcoma model (
n
=
5) by MR imaging (MRI). Following intravenous injection, the blood concentration of Gadomer-17 fell rapidly, whereas that of Gd–BSA was almost constant for the duration of imaging. The areas of enhancement of both MMCAs were comparable. The spatial distribution of Gd–BSA showed good agreement with Evans blue-tagged albumin. Treatment with dexamethasone decreased Gd–BSA enhancement in the tumor. These results suggest that the arsenazo III method is applicable in preparing Gd–BSA to image brain tumors and their response to treatment. This simple method may also be useful for preparing other gadolinium-linked MMCAs. |
doi_str_mv | 10.1016/j.jneumeth.2006.05.013 |
format | Article |
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o-arsenophenylazo)-1,8-dihydroxynaphthalene-3,6-disulfonic acid (arsenazo III) was performed to check for the appearance of free gadolinium during preparation and to quantify the Gd content in the final product. The complex was purified by dialysis, concentrated by lyophilyzation and characterized by magnetic resonance (MR) proton relaxation times. The resultant product had a molecular weight of about 90
kDa, Gd:BSA ratio of 14:1, and
T
1 and
T
2 relaxation times of 128.3 and 48.9
ms, respectively, at a field strength of 7
Tesla (T) and at 20% concentration. Contrast enhancement of Gadomer-17 (a dendritic MMCA) and Gd-linked to BSA (Gd–BSA) was sequentially evaluated in a rat brain gliosarcoma model (
n
=
5) by MR imaging (MRI). Following intravenous injection, the blood concentration of Gadomer-17 fell rapidly, whereas that of Gd–BSA was almost constant for the duration of imaging. The areas of enhancement of both MMCAs were comparable. The spatial distribution of Gd–BSA showed good agreement with Evans blue-tagged albumin. Treatment with dexamethasone decreased Gd–BSA enhancement in the tumor. These results suggest that the arsenazo III method is applicable in preparing Gd–BSA to image brain tumors and their response to treatment. This simple method may also be useful for preparing other gadolinium-linked MMCAs.</description><identifier>ISSN: 0165-0270</identifier><identifier>EISSN: 1872-678X</identifier><identifier>DOI: 10.1016/j.jneumeth.2006.05.013</identifier><identifier>PMID: 16769125</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Arsenazo III - chemistry ; Brain Neoplasms - diagnostic imaging ; Brain tumor ; Contrast Media - chemical synthesis ; Contrast Media - chemistry ; Electrophoresis, Polyacrylamide Gel ; Fluorescent Antibody Technique ; Gadolinium - analysis ; Gadolinium - chemistry ; Gadomer-17 ; Gd–DTPA ; Gliosarcoma - diagnostic imaging ; Magnetic Resonance Imaging ; Male ; MRI ; Radionuclide Imaging ; Rats ; Rats, Inbred F344 ; Serum Albumin, Bovine - chemistry</subject><ispartof>Journal of neuroscience methods, 2006-10, Vol.157 (2), p.238-245</ispartof><rights>2006 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c366t-21623ae85f44f6f9a6526b3457596b742a43549dc873e792195fc7ee006b4e193</citedby><cites>FETCH-LOGICAL-c366t-21623ae85f44f6f9a6526b3457596b742a43549dc873e792195fc7ee006b4e193</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jneumeth.2006.05.013$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16769125$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nagaraja, Tavarekere N.</creatorcontrib><creatorcontrib>Croxen, Richard L.</creatorcontrib><creatorcontrib>Panda, Swayamprava</creatorcontrib><creatorcontrib>Knight, Robert A.</creatorcontrib><creatorcontrib>Keenan, Kelly A.</creatorcontrib><creatorcontrib>Brown, Stephen L.</creatorcontrib><creatorcontrib>Fenstermacher, Joseph D.</creatorcontrib><creatorcontrib>Ewing, James R.</creatorcontrib><title>Application of arsenazo III in the preparation and characterization of an albumin-linked, gadolinium-based macromolecular magnetic resonance contrast agent</title><title>Journal of neuroscience methods</title><addtitle>J Neurosci Methods</addtitle><description>A macromolecular magnetic resonance contrast agent (MMCA) was prepared by linking bovine serum albumin (BSA) to gadolinium (Gd) via a chelating agent, diethylenetriaminepentaacetic acid (DTPA). Colorimetric testing with 2,7-bis(
o-arsenophenylazo)-1,8-dihydroxynaphthalene-3,6-disulfonic acid (arsenazo III) was performed to check for the appearance of free gadolinium during preparation and to quantify the Gd content in the final product. The complex was purified by dialysis, concentrated by lyophilyzation and characterized by magnetic resonance (MR) proton relaxation times. The resultant product had a molecular weight of about 90
kDa, Gd:BSA ratio of 14:1, and
T
1 and
T
2 relaxation times of 128.3 and 48.9
ms, respectively, at a field strength of 7
Tesla (T) and at 20% concentration. Contrast enhancement of Gadomer-17 (a dendritic MMCA) and Gd-linked to BSA (Gd–BSA) was sequentially evaluated in a rat brain gliosarcoma model (
n
=
5) by MR imaging (MRI). Following intravenous injection, the blood concentration of Gadomer-17 fell rapidly, whereas that of Gd–BSA was almost constant for the duration of imaging. The areas of enhancement of both MMCAs were comparable. The spatial distribution of Gd–BSA showed good agreement with Evans blue-tagged albumin. Treatment with dexamethasone decreased Gd–BSA enhancement in the tumor. These results suggest that the arsenazo III method is applicable in preparing Gd–BSA to image brain tumors and their response to treatment. This simple method may also be useful for preparing other gadolinium-linked MMCAs.</description><subject>Animals</subject><subject>Arsenazo III - chemistry</subject><subject>Brain Neoplasms - diagnostic imaging</subject><subject>Brain tumor</subject><subject>Contrast Media - chemical synthesis</subject><subject>Contrast Media - chemistry</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Fluorescent Antibody Technique</subject><subject>Gadolinium - analysis</subject><subject>Gadolinium - chemistry</subject><subject>Gadomer-17</subject><subject>Gd–DTPA</subject><subject>Gliosarcoma - diagnostic imaging</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>MRI</subject><subject>Radionuclide Imaging</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Serum Albumin, Bovine - chemistry</subject><issn>0165-0270</issn><issn>1872-678X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9u3CAQh1HVqNmmfYWIU0-1yx8D9q1R1CYrReolkXJDGI932drgAo7UvEpftkS7VY49wYjvx2jmQ-iSkpoSKr8c6oOHdYa8rxkhsiaiJpS_QRvaKlZJ1T6-RZsCioowRc7R-5QOhJCmI_IdOqdSyY4ysUF_rpZlctZkFzwOIzYxgTfPAW-3W-w8znvAS4TFxCNi_IDtvlQ2Q3TPr7nyNPXr7Hw1Of8Ths94Z4ZQ7m6dq94kGPBsbAxzmMCuk4ml3HnIzuIIKXjjLWAbfI4mZWx24PMHdDaaKcHH03mBHr5_u7--re5-3Gyvr-4qy6XMFaOScQOtGJtmlGNnpGCy541QopO9aphpuGi6wbaKg-oY7cRoFUBZW98A7fgF-nT8d4nh1wop69klC9NkPIQ1adm2gnPOCiiPYJkjpQijXqKbTfytKdEvWvRB_9OiX7RoInTRUoKXpw5rP8PwGjt5KMDXIwBlzicHUSfroKxkcBFs1kNw_-vxFxXEpTg</recordid><startdate>20061030</startdate><enddate>20061030</enddate><creator>Nagaraja, Tavarekere N.</creator><creator>Croxen, Richard L.</creator><creator>Panda, Swayamprava</creator><creator>Knight, Robert A.</creator><creator>Keenan, Kelly A.</creator><creator>Brown, Stephen L.</creator><creator>Fenstermacher, Joseph D.</creator><creator>Ewing, James R.</creator><general>Elsevier B.V</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></search><sort><creationdate>20061030</creationdate><title>Application of arsenazo III in the preparation and characterization of an albumin-linked, gadolinium-based macromolecular magnetic resonance contrast agent</title><author>Nagaraja, Tavarekere N. ; Croxen, Richard L. ; Panda, Swayamprava ; Knight, Robert A. ; Keenan, Kelly A. ; Brown, Stephen L. ; Fenstermacher, Joseph D. ; Ewing, James R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c366t-21623ae85f44f6f9a6526b3457596b742a43549dc873e792195fc7ee006b4e193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Arsenazo III - chemistry</topic><topic>Brain Neoplasms - diagnostic imaging</topic><topic>Brain tumor</topic><topic>Contrast Media - chemical synthesis</topic><topic>Contrast Media - chemistry</topic><topic>Electrophoresis, Polyacrylamide Gel</topic><topic>Fluorescent Antibody Technique</topic><topic>Gadolinium - analysis</topic><topic>Gadolinium - chemistry</topic><topic>Gadomer-17</topic><topic>Gd–DTPA</topic><topic>Gliosarcoma - diagnostic imaging</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>MRI</topic><topic>Radionuclide Imaging</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Serum Albumin, Bovine - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nagaraja, Tavarekere N.</creatorcontrib><creatorcontrib>Croxen, Richard L.</creatorcontrib><creatorcontrib>Panda, Swayamprava</creatorcontrib><creatorcontrib>Knight, Robert A.</creatorcontrib><creatorcontrib>Keenan, Kelly A.</creatorcontrib><creatorcontrib>Brown, Stephen L.</creatorcontrib><creatorcontrib>Fenstermacher, Joseph D.</creatorcontrib><creatorcontrib>Ewing, James R.</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><jtitle>Journal of neuroscience methods</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nagaraja, Tavarekere N.</au><au>Croxen, Richard L.</au><au>Panda, Swayamprava</au><au>Knight, Robert A.</au><au>Keenan, Kelly A.</au><au>Brown, Stephen L.</au><au>Fenstermacher, Joseph D.</au><au>Ewing, James R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Application of arsenazo III in the preparation and characterization of an albumin-linked, gadolinium-based macromolecular magnetic resonance contrast agent</atitle><jtitle>Journal of neuroscience methods</jtitle><addtitle>J Neurosci Methods</addtitle><date>2006-10-30</date><risdate>2006</risdate><volume>157</volume><issue>2</issue><spage>238</spage><epage>245</epage><pages>238-245</pages><issn>0165-0270</issn><eissn>1872-678X</eissn><abstract>A macromolecular magnetic resonance contrast agent (MMCA) was prepared by linking bovine serum albumin (BSA) to gadolinium (Gd) via a chelating agent, diethylenetriaminepentaacetic acid (DTPA). Colorimetric testing with 2,7-bis(
o-arsenophenylazo)-1,8-dihydroxynaphthalene-3,6-disulfonic acid (arsenazo III) was performed to check for the appearance of free gadolinium during preparation and to quantify the Gd content in the final product. The complex was purified by dialysis, concentrated by lyophilyzation and characterized by magnetic resonance (MR) proton relaxation times. The resultant product had a molecular weight of about 90
kDa, Gd:BSA ratio of 14:1, and
T
1 and
T
2 relaxation times of 128.3 and 48.9
ms, respectively, at a field strength of 7
Tesla (T) and at 20% concentration. Contrast enhancement of Gadomer-17 (a dendritic MMCA) and Gd-linked to BSA (Gd–BSA) was sequentially evaluated in a rat brain gliosarcoma model (
n
=
5) by MR imaging (MRI). Following intravenous injection, the blood concentration of Gadomer-17 fell rapidly, whereas that of Gd–BSA was almost constant for the duration of imaging. The areas of enhancement of both MMCAs were comparable. The spatial distribution of Gd–BSA showed good agreement with Evans blue-tagged albumin. Treatment with dexamethasone decreased Gd–BSA enhancement in the tumor. These results suggest that the arsenazo III method is applicable in preparing Gd–BSA to image brain tumors and their response to treatment. This simple method may also be useful for preparing other gadolinium-linked MMCAs.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>16769125</pmid><doi>10.1016/j.jneumeth.2006.05.013</doi><tpages>8</tpages></addata></record> |
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subjects | Animals Arsenazo III - chemistry Brain Neoplasms - diagnostic imaging Brain tumor Contrast Media - chemical synthesis Contrast Media - chemistry Electrophoresis, Polyacrylamide Gel Fluorescent Antibody Technique Gadolinium - analysis Gadolinium - chemistry Gadomer-17 Gd–DTPA Gliosarcoma - diagnostic imaging Magnetic Resonance Imaging Male MRI Radionuclide Imaging Rats Rats, Inbred F344 Serum Albumin, Bovine - chemistry |
title | Application of arsenazo III in the preparation and characterization of an albumin-linked, gadolinium-based macromolecular magnetic resonance contrast agent |
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