Molecular Imaging of CXCR4 Receptor Expression in Human Cancer Xenografts with [64Cu]AMD3100 Positron Emission Tomography
The chemokine receptor CXCR4 and its cognate ligand CXCL12 are pivotal for establishing metastases from many tumor types. Thus, CXCR4 may offer a cell surface target for molecular imaging of metastases, assisting diagnosis, staging, and therapeutic monitoring. Furthermore, noninvasive detection of C...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2010-05, Vol.70 (10), p.3935-3944 |
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| creator | NIMMAGADDA, Sridhar PULLAMBHATLA, Mrudula STONE, Kristie GREEN, Gilbert BHUJWALLA, Zaver M POMPER, Martin G |
| description | The chemokine receptor CXCR4 and its cognate ligand CXCL12 are pivotal for establishing metastases from many tumor types. Thus, CXCR4 may offer a cell surface target for molecular imaging of metastases, assisting diagnosis, staging, and therapeutic monitoring. Furthermore, noninvasive detection of CXCR4 status of a primary tumor may provide an index of the metastatic potential of the lesion. Here, we report the development and evaluation of [(64)Cu]AMD3100, a positron-emitting analogue of the stem cell mobilizing agent plerixafor to image CXCR4 in human tumor xenografts preselected for graded expression of this receptor. This imaging method was evaluated in lung metastases derived from human MDA-MB-231 breast cancer cells. Ex vivo biodistribution studies, performed to validate the in vivo imaging data, confirmed the ability of [(64)Cu]AMD3100 to image CXCR4 expression. Our findings show the feasibility of imaging CXCR4 by positron emission tomography using a clinically approved agent as a molecular scaffold. |
| doi_str_mv | 10.1158/0008-5472.CAN-09-4396 |
| format | Article |
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Thus, CXCR4 may offer a cell surface target for molecular imaging of metastases, assisting diagnosis, staging, and therapeutic monitoring. Furthermore, noninvasive detection of CXCR4 status of a primary tumor may provide an index of the metastatic potential of the lesion. Here, we report the development and evaluation of [(64)Cu]AMD3100, a positron-emitting analogue of the stem cell mobilizing agent plerixafor to image CXCR4 in human tumor xenografts preselected for graded expression of this receptor. This imaging method was evaluated in lung metastases derived from human MDA-MB-231 breast cancer cells. Ex vivo biodistribution studies, performed to validate the in vivo imaging data, confirmed the ability of [(64)Cu]AMD3100 to image CXCR4 expression. Our findings show the feasibility of imaging CXCR4 by positron emission tomography using a clinically approved agent as a molecular scaffold.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-09-4396</identifier><identifier>PMID: 20460522</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Antineoplastic agents ; Biological and medical sciences ; Blotting, Western ; Copper Radioisotopes ; Female ; Flow Cytometry ; Heterocyclic Compounds ; Humans ; Immunoenzyme Techniques ; Lung Neoplasms - diagnostic imaging ; Lung Neoplasms - metabolism ; Lung Neoplasms - secondary ; Mammary Neoplasms, Experimental - diagnostic imaging ; Mammary Neoplasms, Experimental - metabolism ; Mammary Neoplasms, Experimental - pathology ; Medical sciences ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Pharmacology. Drug treatments ; Positron-Emission Tomography ; Receptors, CXCR4 - antagonists & inhibitors ; Receptors, CXCR4 - metabolism ; Tissue Distribution ; Tomography, X-Ray Computed ; Tumors</subject><ispartof>Cancer research (Chicago, Ill.), 2010-05, Vol.70 (10), p.3935-3944</ispartof><rights>2015 INIST-CNRS</rights><rights>(c)2010 AACR.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-c9c076db6b524bf62354ededadc7a6b0a5fd90a80ddbd88648163132eba935d13</citedby><cites>FETCH-LOGICAL-c440t-c9c076db6b524bf62354ededadc7a6b0a5fd90a80ddbd88648163132eba935d13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,778,782,883,3345,27911,27912</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22774128$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20460522$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>NIMMAGADDA, Sridhar</creatorcontrib><creatorcontrib>PULLAMBHATLA, Mrudula</creatorcontrib><creatorcontrib>STONE, Kristie</creatorcontrib><creatorcontrib>GREEN, Gilbert</creatorcontrib><creatorcontrib>BHUJWALLA, Zaver M</creatorcontrib><creatorcontrib>POMPER, Martin G</creatorcontrib><title>Molecular Imaging of CXCR4 Receptor Expression in Human Cancer Xenografts with [64Cu]AMD3100 Positron Emission Tomography</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>The chemokine receptor CXCR4 and its cognate ligand CXCL12 are pivotal for establishing metastases from many tumor types. Thus, CXCR4 may offer a cell surface target for molecular imaging of metastases, assisting diagnosis, staging, and therapeutic monitoring. Furthermore, noninvasive detection of CXCR4 status of a primary tumor may provide an index of the metastatic potential of the lesion. Here, we report the development and evaluation of [(64)Cu]AMD3100, a positron-emitting analogue of the stem cell mobilizing agent plerixafor to image CXCR4 in human tumor xenografts preselected for graded expression of this receptor. This imaging method was evaluated in lung metastases derived from human MDA-MB-231 breast cancer cells. Ex vivo biodistribution studies, performed to validate the in vivo imaging data, confirmed the ability of [(64)Cu]AMD3100 to image CXCR4 expression. Our findings show the feasibility of imaging CXCR4 by positron emission tomography using a clinically approved agent as a molecular scaffold.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Copper Radioisotopes</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Heterocyclic Compounds</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Lung Neoplasms - diagnostic imaging</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - secondary</subject><subject>Mammary Neoplasms, Experimental - diagnostic imaging</subject><subject>Mammary Neoplasms, Experimental - metabolism</subject><subject>Mammary Neoplasms, Experimental - pathology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Pharmacology. Drug treatments</subject><subject>Positron-Emission Tomography</subject><subject>Receptors, CXCR4 - antagonists & inhibitors</subject><subject>Receptors, CXCR4 - metabolism</subject><subject>Tissue Distribution</subject><subject>Tomography, X-Ray Computed</subject><subject>Tumors</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkV-L1DAUxYMo7rj6EZS8-Nj15m_TF2Goo7uwq7KssCAS0iSdibRNSTrqfHtbZh31KVzyO-dezkHoJYELQoR6AwCqELykF_X6YwFVwVklH6EVEUwVJefiMVqdmDP0LOfv8ygIiKfojAKXIChdocNN7Lzddybhq95sw7DFscX1fX3L8a23fpxiwptfY_I5hzjgMODLfW8GXJvB-oTv_RC3ybRTxj_DtMNfJa_339Y37xgBwJ9jDlOaZZs-HPV3sV_4cXd4jp60psv-xcN7jr6839zVl8X1pw9X9fq6sJzDVNjKQildIxtBedNKygT3zjvjbGlkA0a0rgKjwLnGKSW5IpIRRn1jKiYcYefo7dF33De9d9YPUzKdHlPoTTroaIL-_2cIO72NPzRVJScVnQ3E0cCmmHPy7UlLQC9d6CVnveSs5y40VHrpYta9-nfxSfUn_Bl4_QCYbE3XpjnSkP9ytJwPoIr9Bkp5lB4</recordid><startdate>20100515</startdate><enddate>20100515</enddate><creator>NIMMAGADDA, Sridhar</creator><creator>PULLAMBHATLA, Mrudula</creator><creator>STONE, Kristie</creator><creator>GREEN, Gilbert</creator><creator>BHUJWALLA, Zaver M</creator><creator>POMPER, Martin G</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><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>5PM</scope></search><sort><creationdate>20100515</creationdate><title>Molecular Imaging of CXCR4 Receptor Expression in Human Cancer Xenografts with [64Cu]AMD3100 Positron Emission Tomography</title><author>NIMMAGADDA, Sridhar ; PULLAMBHATLA, Mrudula ; STONE, Kristie ; GREEN, Gilbert ; BHUJWALLA, Zaver M ; POMPER, Martin G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-c9c076db6b524bf62354ededadc7a6b0a5fd90a80ddbd88648163132eba935d13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Copper Radioisotopes</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Heterocyclic Compounds</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Lung Neoplasms - diagnostic imaging</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - secondary</topic><topic>Mammary Neoplasms, Experimental - diagnostic imaging</topic><topic>Mammary Neoplasms, Experimental - metabolism</topic><topic>Mammary Neoplasms, Experimental - pathology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Pharmacology. 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Thus, CXCR4 may offer a cell surface target for molecular imaging of metastases, assisting diagnosis, staging, and therapeutic monitoring. Furthermore, noninvasive detection of CXCR4 status of a primary tumor may provide an index of the metastatic potential of the lesion. Here, we report the development and evaluation of [(64)Cu]AMD3100, a positron-emitting analogue of the stem cell mobilizing agent plerixafor to image CXCR4 in human tumor xenografts preselected for graded expression of this receptor. This imaging method was evaluated in lung metastases derived from human MDA-MB-231 breast cancer cells. Ex vivo biodistribution studies, performed to validate the in vivo imaging data, confirmed the ability of [(64)Cu]AMD3100 to image CXCR4 expression. 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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Antineoplastic agents Biological and medical sciences Blotting, Western Copper Radioisotopes Female Flow Cytometry Heterocyclic Compounds Humans Immunoenzyme Techniques Lung Neoplasms - diagnostic imaging Lung Neoplasms - metabolism Lung Neoplasms - secondary Mammary Neoplasms, Experimental - diagnostic imaging Mammary Neoplasms, Experimental - metabolism Mammary Neoplasms, Experimental - pathology Medical sciences Mice Mice, Inbred NOD Mice, SCID Pharmacology. Drug treatments Positron-Emission Tomography Receptors, CXCR4 - antagonists & inhibitors Receptors, CXCR4 - metabolism Tissue Distribution Tomography, X-Ray Computed Tumors |
| title | Molecular Imaging of CXCR4 Receptor Expression in Human Cancer Xenografts with [64Cu]AMD3100 Positron Emission Tomography |
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