SPECT and PET Amino Acid Tracer Influx via System L (h4F2hc-hLAT1) and Its Transstimulation
System L amino acid transport is increased in various types of cancer. The tracer 123I-2-iodotyrosine (2IT), which is accumulated via system L, could thus serve to allow visualization of cancer in vivo. Here, we studied the transport of 125I-2IT by h4F2hc-hLAT1, the major transporter subserving syst...
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| Veröffentlicht in: | The Journal of nuclear medicine (1978) 2004-09, Vol.45 (9), p.1591-1596 |
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| creator | Lahoutte, Tony Caveliers, Vicky Camargo, Simone M.R Franca, Raffaella Ramadan, Tamara Veljkovic, Emilija Mertens, John Bossuyt, Axel Verrey, Francois |
| description | System L amino acid transport is increased in various types of cancer. The tracer 123I-2-iodotyrosine (2IT), which is accumulated via system L, could thus serve to allow visualization of cancer in vivo. Here, we studied the transport of 125I-2IT by h4F2hc-hLAT1, the major transporter subserving system L in growing cells, using the Xenopus laevis oocyte expression system. We compared the apparent affinity of 125I-2IT with that of tyrosine, tested the influence of intracellular methionine availability on the influx rate of this substrate, and then compared the transport of 2IT with that of the other tracers-iodo-alpha-methyltyrosine (IMT), fluoroethyltyrosine (FET), and 2-fluorotyrosine (2FT)-by measuring their transstimulating effect on phenylalanine efflux.
Transport experiments were performed with Xenopus laevis oocytes expressing h4F2hc-hLAT1 (the functional transporter) and oocytes expressing only h4F2hc (negative control). The values obtained for the functional transporter were corrected for endogenous background transport by subtracting the values for the negative controls.
The apparent affinity for 125I-2IT and 3H-tyrosine was 29.3 +/- 9.3 micromol/L and 21.2 +/- 4.2 micromol/L, respectively. The influx rate of 125I-2IT was, similarly to that of 3H-phenylalanine, transstimulated by a factor of > or =3 when the oocytes were preinjected with methionine or phenylalanine. The proportion of preinjected 3H-phenylalanine that effluxed within 90 s in the presence of an extracellular 2IT concentration of 0.1 mmol/L was 4.1% +/- 0.5%, compared with 3.3% +/- 0.4% for extracellular IMT, 1.3% +/- 0.3% for FET, 9.3% +/- 0.8% for 2FT, and 9.1% +/- 0.5% for phenylalanine.
2IT has a high affinity for h4F2hc-hLAT1, comparable to that of natural tyrosine, and its influx rate is transstimulated by intracellular amino acids. The 2IT influx rate is comparable to that of IMT but lower than that of phenylalanine. In contrast to FET, which is only poorly transported, 2FT displays a high influx rate equal to that of phenylalanine. |
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Transport experiments were performed with Xenopus laevis oocytes expressing h4F2hc-hLAT1 (the functional transporter) and oocytes expressing only h4F2hc (negative control). The values obtained for the functional transporter were corrected for endogenous background transport by subtracting the values for the negative controls.
The apparent affinity for 125I-2IT and 3H-tyrosine was 29.3 +/- 9.3 micromol/L and 21.2 +/- 4.2 micromol/L, respectively. The influx rate of 125I-2IT was, similarly to that of 3H-phenylalanine, transstimulated by a factor of > or =3 when the oocytes were preinjected with methionine or phenylalanine. The proportion of preinjected 3H-phenylalanine that effluxed within 90 s in the presence of an extracellular 2IT concentration of 0.1 mmol/L was 4.1% +/- 0.5%, compared with 3.3% +/- 0.4% for extracellular IMT, 1.3% +/- 0.3% for FET, 9.3% +/- 0.8% for 2FT, and 9.1% +/- 0.5% for phenylalanine.
2IT has a high affinity for h4F2hc-hLAT1, comparable to that of natural tyrosine, and its influx rate is transstimulated by intracellular amino acids. The 2IT influx rate is comparable to that of IMT but lower than that of phenylalanine. In contrast to FET, which is only poorly transported, 2FT displays a high influx rate equal to that of phenylalanine.</description><identifier>ISSN: 0161-5505</identifier><identifier>EISSN: 1535-5667</identifier><identifier>PMID: 15347729</identifier><identifier>CODEN: JNMEAQ</identifier><language>eng</language><publisher>United States: Soc Nuclear Med</publisher><subject>Amino Acid Transport Systems - metabolism ; Amino Acids - pharmacokinetics ; Animals ; Humans ; Isotope Labeling - methods ; Metabolic Clearance Rate ; Monoiodotyrosine - metabolism ; Monoiodotyrosine - pharmacokinetics ; Oocytes - diagnostic imaging ; Oocytes - metabolism ; Radioisotope Dilution Technique ; Radiopharmaceuticals - pharmacokinetics ; Tomography, Emission-Computed - methods ; Tomography, Emission-Computed, Single-Photon - methods ; Xenopus laevis</subject><ispartof>The Journal of nuclear medicine (1978), 2004-09, Vol.45 (9), p.1591-1596</ispartof><rights>Copyright Society of Nuclear Medicine Sep 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15347729$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lahoutte, Tony</creatorcontrib><creatorcontrib>Caveliers, Vicky</creatorcontrib><creatorcontrib>Camargo, Simone M.R</creatorcontrib><creatorcontrib>Franca, Raffaella</creatorcontrib><creatorcontrib>Ramadan, Tamara</creatorcontrib><creatorcontrib>Veljkovic, Emilija</creatorcontrib><creatorcontrib>Mertens, John</creatorcontrib><creatorcontrib>Bossuyt, Axel</creatorcontrib><creatorcontrib>Verrey, Francois</creatorcontrib><title>SPECT and PET Amino Acid Tracer Influx via System L (h4F2hc-hLAT1) and Its Transstimulation</title><title>The Journal of nuclear medicine (1978)</title><addtitle>J Nucl Med</addtitle><description>System L amino acid transport is increased in various types of cancer. The tracer 123I-2-iodotyrosine (2IT), which is accumulated via system L, could thus serve to allow visualization of cancer in vivo. Here, we studied the transport of 125I-2IT by h4F2hc-hLAT1, the major transporter subserving system L in growing cells, using the Xenopus laevis oocyte expression system. We compared the apparent affinity of 125I-2IT with that of tyrosine, tested the influence of intracellular methionine availability on the influx rate of this substrate, and then compared the transport of 2IT with that of the other tracers-iodo-alpha-methyltyrosine (IMT), fluoroethyltyrosine (FET), and 2-fluorotyrosine (2FT)-by measuring their transstimulating effect on phenylalanine efflux.
Transport experiments were performed with Xenopus laevis oocytes expressing h4F2hc-hLAT1 (the functional transporter) and oocytes expressing only h4F2hc (negative control). The values obtained for the functional transporter were corrected for endogenous background transport by subtracting the values for the negative controls.
The apparent affinity for 125I-2IT and 3H-tyrosine was 29.3 +/- 9.3 micromol/L and 21.2 +/- 4.2 micromol/L, respectively. The influx rate of 125I-2IT was, similarly to that of 3H-phenylalanine, transstimulated by a factor of > or =3 when the oocytes were preinjected with methionine or phenylalanine. The proportion of preinjected 3H-phenylalanine that effluxed within 90 s in the presence of an extracellular 2IT concentration of 0.1 mmol/L was 4.1% +/- 0.5%, compared with 3.3% +/- 0.4% for extracellular IMT, 1.3% +/- 0.3% for FET, 9.3% +/- 0.8% for 2FT, and 9.1% +/- 0.5% for phenylalanine.
2IT has a high affinity for h4F2hc-hLAT1, comparable to that of natural tyrosine, and its influx rate is transstimulated by intracellular amino acids. The 2IT influx rate is comparable to that of IMT but lower than that of phenylalanine. In contrast to FET, which is only poorly transported, 2FT displays a high influx rate equal to that of phenylalanine.</description><subject>Amino Acid Transport Systems - metabolism</subject><subject>Amino Acids - pharmacokinetics</subject><subject>Animals</subject><subject>Humans</subject><subject>Isotope Labeling - methods</subject><subject>Metabolic Clearance Rate</subject><subject>Monoiodotyrosine - metabolism</subject><subject>Monoiodotyrosine - pharmacokinetics</subject><subject>Oocytes - diagnostic imaging</subject><subject>Oocytes - metabolism</subject><subject>Radioisotope Dilution Technique</subject><subject>Radiopharmaceuticals - pharmacokinetics</subject><subject>Tomography, Emission-Computed - methods</subject><subject>Tomography, Emission-Computed, Single-Photon - methods</subject><subject>Xenopus laevis</subject><issn>0161-5505</issn><issn>1535-5667</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpd0E1Lw0AQBuBFFFurf0EWD34cAvud5BhKq4WAhcaTh7BJNmZLsqm7idp_79bqRRiYyzMvM3MCpphTHnAhwlMwRVjggHPEJ-DCuS1CSERRdA4mHrEwJPEUvG7Wi3kGpangepHBpNOmh0mpK5hZWSoLV6Zuxy_4oSXc7N2gOpjC-4YtSVMGTZpk-OFneDW4w4RxbtDd2MpB9-YSnNWyderqt8_Ay3KRzZ-C9PlxNU_SoCFCDEFZI0xUIVHEFQpxHDGOKkkQ4yWjMVUyxJQVHOMCSVXV_hykIhoxiYqICMbpDNwec3e2fx-VG_JOu1K1rTSqH10uhI-kBHl48w9u-9Eav1tOcOyL8tCj6180Fp2q8p3VnbT7_O9nHtwdQaPfmk9tVW7GslXSHvTWdIznsdcxpt99rXI7</recordid><startdate>20040901</startdate><enddate>20040901</enddate><creator>Lahoutte, Tony</creator><creator>Caveliers, Vicky</creator><creator>Camargo, Simone M.R</creator><creator>Franca, Raffaella</creator><creator>Ramadan, Tamara</creator><creator>Veljkovic, Emilija</creator><creator>Mertens, John</creator><creator>Bossuyt, Axel</creator><creator>Verrey, Francois</creator><general>Soc Nuclear Med</general><general>Society of Nuclear Medicine</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>4T-</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>M7Z</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>20040901</creationdate><title>SPECT and PET Amino Acid Tracer Influx via System L (h4F2hc-hLAT1) and Its Transstimulation</title><author>Lahoutte, Tony ; Caveliers, Vicky ; Camargo, Simone M.R ; Franca, Raffaella ; Ramadan, Tamara ; Veljkovic, Emilija ; Mertens, John ; Bossuyt, Axel ; Verrey, Francois</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h266t-cf012eba085e07198450da2045c4393ea7134b511b0aedf5050e8384a0b826453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Amino Acid Transport Systems - metabolism</topic><topic>Amino Acids - pharmacokinetics</topic><topic>Animals</topic><topic>Humans</topic><topic>Isotope Labeling - methods</topic><topic>Metabolic Clearance Rate</topic><topic>Monoiodotyrosine - metabolism</topic><topic>Monoiodotyrosine - pharmacokinetics</topic><topic>Oocytes - diagnostic imaging</topic><topic>Oocytes - metabolism</topic><topic>Radioisotope Dilution Technique</topic><topic>Radiopharmaceuticals - pharmacokinetics</topic><topic>Tomography, Emission-Computed - methods</topic><topic>Tomography, Emission-Computed, Single-Photon - methods</topic><topic>Xenopus laevis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lahoutte, Tony</creatorcontrib><creatorcontrib>Caveliers, Vicky</creatorcontrib><creatorcontrib>Camargo, Simone M.R</creatorcontrib><creatorcontrib>Franca, Raffaella</creatorcontrib><creatorcontrib>Ramadan, Tamara</creatorcontrib><creatorcontrib>Veljkovic, Emilija</creatorcontrib><creatorcontrib>Mertens, John</creatorcontrib><creatorcontrib>Bossuyt, Axel</creatorcontrib><creatorcontrib>Verrey, Francois</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Docstoc</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of nuclear medicine (1978)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lahoutte, Tony</au><au>Caveliers, Vicky</au><au>Camargo, Simone M.R</au><au>Franca, Raffaella</au><au>Ramadan, Tamara</au><au>Veljkovic, Emilija</au><au>Mertens, John</au><au>Bossuyt, Axel</au><au>Verrey, Francois</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SPECT and PET Amino Acid Tracer Influx via System L (h4F2hc-hLAT1) and Its Transstimulation</atitle><jtitle>The Journal of nuclear medicine (1978)</jtitle><addtitle>J Nucl Med</addtitle><date>2004-09-01</date><risdate>2004</risdate><volume>45</volume><issue>9</issue><spage>1591</spage><epage>1596</epage><pages>1591-1596</pages><issn>0161-5505</issn><eissn>1535-5667</eissn><coden>JNMEAQ</coden><abstract>System L amino acid transport is increased in various types of cancer. The tracer 123I-2-iodotyrosine (2IT), which is accumulated via system L, could thus serve to allow visualization of cancer in vivo. Here, we studied the transport of 125I-2IT by h4F2hc-hLAT1, the major transporter subserving system L in growing cells, using the Xenopus laevis oocyte expression system. We compared the apparent affinity of 125I-2IT with that of tyrosine, tested the influence of intracellular methionine availability on the influx rate of this substrate, and then compared the transport of 2IT with that of the other tracers-iodo-alpha-methyltyrosine (IMT), fluoroethyltyrosine (FET), and 2-fluorotyrosine (2FT)-by measuring their transstimulating effect on phenylalanine efflux.
Transport experiments were performed with Xenopus laevis oocytes expressing h4F2hc-hLAT1 (the functional transporter) and oocytes expressing only h4F2hc (negative control). The values obtained for the functional transporter were corrected for endogenous background transport by subtracting the values for the negative controls.
The apparent affinity for 125I-2IT and 3H-tyrosine was 29.3 +/- 9.3 micromol/L and 21.2 +/- 4.2 micromol/L, respectively. The influx rate of 125I-2IT was, similarly to that of 3H-phenylalanine, transstimulated by a factor of > or =3 when the oocytes were preinjected with methionine or phenylalanine. The proportion of preinjected 3H-phenylalanine that effluxed within 90 s in the presence of an extracellular 2IT concentration of 0.1 mmol/L was 4.1% +/- 0.5%, compared with 3.3% +/- 0.4% for extracellular IMT, 1.3% +/- 0.3% for FET, 9.3% +/- 0.8% for 2FT, and 9.1% +/- 0.5% for phenylalanine.
2IT has a high affinity for h4F2hc-hLAT1, comparable to that of natural tyrosine, and its influx rate is transstimulated by intracellular amino acids. The 2IT influx rate is comparable to that of IMT but lower than that of phenylalanine. In contrast to FET, which is only poorly transported, 2FT displays a high influx rate equal to that of phenylalanine.</abstract><cop>United States</cop><pub>Soc Nuclear Med</pub><pmid>15347729</pmid><tpages>6</tpages></addata></record> |
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| subjects | Amino Acid Transport Systems - metabolism Amino Acids - pharmacokinetics Animals Humans Isotope Labeling - methods Metabolic Clearance Rate Monoiodotyrosine - metabolism Monoiodotyrosine - pharmacokinetics Oocytes - diagnostic imaging Oocytes - metabolism Radioisotope Dilution Technique Radiopharmaceuticals - pharmacokinetics Tomography, Emission-Computed - methods Tomography, Emission-Computed, Single-Photon - methods Xenopus laevis |
| title | SPECT and PET Amino Acid Tracer Influx via System L (h4F2hc-hLAT1) and Its Transstimulation |
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