Loading…

Radiosynthesis, in vitro and preliminary biological evaluation of 18 F2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid, a novel alanine serine cysteine transporter 2 inhibitor-based positron emission tomography tracer

The metabolic alterations in tumors make it possible to visualize the latter by means of positron emission tomography, enabling diagnosis and providing metabolic information. The alanine serine cysteine transporter-2 (ASCT-2) is the main transporter of glutamine and is upregulated in several tumors....

Full description

Saved in:
Bibliographic Details
Published in:Journal of labelled compounds & radiopharmaceuticals 2020-08, Vol.63 (10), p.442
Main Authors: Baguet, Tristan, Bouton, Jakob, Janssens, Jonas, Pauwelyn, Glenn, Verhoeven, Jeroen, Descamps, Benedicte, Van Calenbergh, Serge, Vanhove, Christian, De Vos, Filip
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by
cites
container_end_page
container_issue 10
container_start_page 442
container_title Journal of labelled compounds & radiopharmaceuticals
container_volume 63
creator Baguet, Tristan
Bouton, Jakob
Janssens, Jonas
Pauwelyn, Glenn
Verhoeven, Jeroen
Descamps, Benedicte
Van Calenbergh, Serge
Vanhove, Christian
De Vos, Filip
description The metabolic alterations in tumors make it possible to visualize the latter by means of positron emission tomography, enabling diagnosis and providing metabolic information. The alanine serine cysteine transporter-2 (ASCT-2) is the main transporter of glutamine and is upregulated in several tumors. Therefore, a good positron emission tracer targeting this transport protein would have substantial value. Hence, the aim of this study is to develop a fluorine-18-labeled version of a V-9302 analogue, one of the most potent inhibitors of ASCT-2. The precursor was labeled with fluorine-18 via a nucleophilic substitution of the corresponding benzylic bromide. The cold reference product was subjected to in vitro assays with [3 H]glutamine in a PC-3 and F98 cell line to determine the affinity for both the human and rat ASCT-2. To evaluate the tracer potential dynamic μPET, images were acquired in a mouse xenograft model for prostate cancer. The tracer could be synthesized with an overall nondecay corrected yield of 3.66 ± 1.90%. in vitro experiments show inhibitor constants Ki of 90 and 125 μM for the PC-3 and F98 cells, respectively. The experiments in the PC-3 xenograft demonstrate a low uptake in the tumor tissue. We have successfully synthesized the radiotracer [18 F]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid. in vitro experiments show a good affinity for both the human and rat ASCT-2. However, the tracer suffers from poor in vivo tumor uptake in the PC-3 model. Briefly, we present the first fluorine-18-labeled derivative of compound V-9302, a promising novel ASCT-2 blocker used for inhibition of tumor growth.The metabolic alterations in tumors make it possible to visualize the latter by means of positron emission tomography, enabling diagnosis and providing metabolic information. The alanine serine cysteine transporter-2 (ASCT-2) is the main transporter of glutamine and is upregulated in several tumors. Therefore, a good positron emission tracer targeting this transport protein would have substantial value. Hence, the aim of this study is to develop a fluorine-18-labeled version of a V-9302 analogue, one of the most potent inhibitors of ASCT-2. The precursor was labeled with fluorine-18 via a nucleophilic substitution of the corresponding benzylic bromide. The cold reference product was subjected to in vitro assays with [3 H]glutamine in a PC-3 and F98 cell line to determine the affinity for both the hu
doi_str_mv 10.1002/jlcr.3863
format article
fullrecord <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_miscellaneous_2408200287</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2408200287</sourcerecordid><originalsourceid>FETCH-proquest_miscellaneous_24082002873</originalsourceid><addsrcrecordid>eNqVUD1Pw0AMDQgkCnTgH3hMpabkS9DOiIoZsVdO6jauLudwvlSEX88FOiAxMVh-tp8_nqPoLksXWZrm9wdTu0WxfCjOo0mWrlZJVpTlxS98FV2rHtI0xGU5OZu-4pZFB-sbUtY5sIUjeyeAdgudI8MtW3QDVCxG9lyjATqi6dGzWJAdZEtY5wkGmiRlEsd5sCLZmV6cVGQ_BzOTj2F2gqdy_FNvyTch-Zf2PW5W9R6tcA1Y83YOCFaOZAANWrYESm509aCeRuAdWu3EeXKQByUNV-zFJRUqBTGiozAL1LLqeLyXVvYOu2YYW2tyt9HlDo3S9ORvonj9_Pb0knRO3ntSvwmtNZmwn6TXTV6myzy8fflY_IP6BXSkjNE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2408200287</pqid></control><display><type>article</type><title>Radiosynthesis, in vitro and preliminary biological evaluation of 18 F2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid, a novel alanine serine cysteine transporter 2 inhibitor-based positron emission tomography tracer</title><source>Wiley-Blackwell Read &amp; Publish Collection</source><creator>Baguet, Tristan ; Bouton, Jakob ; Janssens, Jonas ; Pauwelyn, Glenn ; Verhoeven, Jeroen ; Descamps, Benedicte ; Van Calenbergh, Serge ; Vanhove, Christian ; De Vos, Filip</creator><creatorcontrib>Baguet, Tristan ; Bouton, Jakob ; Janssens, Jonas ; Pauwelyn, Glenn ; Verhoeven, Jeroen ; Descamps, Benedicte ; Van Calenbergh, Serge ; Vanhove, Christian ; De Vos, Filip</creatorcontrib><description>The metabolic alterations in tumors make it possible to visualize the latter by means of positron emission tomography, enabling diagnosis and providing metabolic information. The alanine serine cysteine transporter-2 (ASCT-2) is the main transporter of glutamine and is upregulated in several tumors. Therefore, a good positron emission tracer targeting this transport protein would have substantial value. Hence, the aim of this study is to develop a fluorine-18-labeled version of a V-9302 analogue, one of the most potent inhibitors of ASCT-2. The precursor was labeled with fluorine-18 via a nucleophilic substitution of the corresponding benzylic bromide. The cold reference product was subjected to in vitro assays with [3 H]glutamine in a PC-3 and F98 cell line to determine the affinity for both the human and rat ASCT-2. To evaluate the tracer potential dynamic μPET, images were acquired in a mouse xenograft model for prostate cancer. The tracer could be synthesized with an overall nondecay corrected yield of 3.66 ± 1.90%. in vitro experiments show inhibitor constants Ki of 90 and 125 μM for the PC-3 and F98 cells, respectively. The experiments in the PC-3 xenograft demonstrate a low uptake in the tumor tissue. We have successfully synthesized the radiotracer [18 F]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid. in vitro experiments show a good affinity for both the human and rat ASCT-2. However, the tracer suffers from poor in vivo tumor uptake in the PC-3 model. Briefly, we present the first fluorine-18-labeled derivative of compound V-9302, a promising novel ASCT-2 blocker used for inhibition of tumor growth.The metabolic alterations in tumors make it possible to visualize the latter by means of positron emission tomography, enabling diagnosis and providing metabolic information. The alanine serine cysteine transporter-2 (ASCT-2) is the main transporter of glutamine and is upregulated in several tumors. Therefore, a good positron emission tracer targeting this transport protein would have substantial value. Hence, the aim of this study is to develop a fluorine-18-labeled version of a V-9302 analogue, one of the most potent inhibitors of ASCT-2. The precursor was labeled with fluorine-18 via a nucleophilic substitution of the corresponding benzylic bromide. The cold reference product was subjected to in vitro assays with [3 H]glutamine in a PC-3 and F98 cell line to determine the affinity for both the human and rat ASCT-2. To evaluate the tracer potential dynamic μPET, images were acquired in a mouse xenograft model for prostate cancer. The tracer could be synthesized with an overall nondecay corrected yield of 3.66 ± 1.90%. in vitro experiments show inhibitor constants Ki of 90 and 125 μM for the PC-3 and F98 cells, respectively. The experiments in the PC-3 xenograft demonstrate a low uptake in the tumor tissue. We have successfully synthesized the radiotracer [18 F]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid. in vitro experiments show a good affinity for both the human and rat ASCT-2. However, the tracer suffers from poor in vivo tumor uptake in the PC-3 model. Briefly, we present the first fluorine-18-labeled derivative of compound V-9302, a promising novel ASCT-2 blocker used for inhibition of tumor growth.</description><identifier>ISSN: 1099-1344</identifier><identifier>EISSN: 1099-1344</identifier><identifier>DOI: 10.1002/jlcr.3863</identifier><language>eng</language><ispartof>Journal of labelled compounds &amp; radiopharmaceuticals, 2020-08, Vol.63 (10), p.442</ispartof><rights>2020 John Wiley &amp; Sons, Ltd.</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>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Baguet, Tristan</creatorcontrib><creatorcontrib>Bouton, Jakob</creatorcontrib><creatorcontrib>Janssens, Jonas</creatorcontrib><creatorcontrib>Pauwelyn, Glenn</creatorcontrib><creatorcontrib>Verhoeven, Jeroen</creatorcontrib><creatorcontrib>Descamps, Benedicte</creatorcontrib><creatorcontrib>Van Calenbergh, Serge</creatorcontrib><creatorcontrib>Vanhove, Christian</creatorcontrib><creatorcontrib>De Vos, Filip</creatorcontrib><title>Radiosynthesis, in vitro and preliminary biological evaluation of 18 F2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid, a novel alanine serine cysteine transporter 2 inhibitor-based positron emission tomography tracer</title><title>Journal of labelled compounds &amp; radiopharmaceuticals</title><description>The metabolic alterations in tumors make it possible to visualize the latter by means of positron emission tomography, enabling diagnosis and providing metabolic information. The alanine serine cysteine transporter-2 (ASCT-2) is the main transporter of glutamine and is upregulated in several tumors. Therefore, a good positron emission tracer targeting this transport protein would have substantial value. Hence, the aim of this study is to develop a fluorine-18-labeled version of a V-9302 analogue, one of the most potent inhibitors of ASCT-2. The precursor was labeled with fluorine-18 via a nucleophilic substitution of the corresponding benzylic bromide. The cold reference product was subjected to in vitro assays with [3 H]glutamine in a PC-3 and F98 cell line to determine the affinity for both the human and rat ASCT-2. To evaluate the tracer potential dynamic μPET, images were acquired in a mouse xenograft model for prostate cancer. The tracer could be synthesized with an overall nondecay corrected yield of 3.66 ± 1.90%. in vitro experiments show inhibitor constants Ki of 90 and 125 μM for the PC-3 and F98 cells, respectively. The experiments in the PC-3 xenograft demonstrate a low uptake in the tumor tissue. We have successfully synthesized the radiotracer [18 F]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid. in vitro experiments show a good affinity for both the human and rat ASCT-2. However, the tracer suffers from poor in vivo tumor uptake in the PC-3 model. Briefly, we present the first fluorine-18-labeled derivative of compound V-9302, a promising novel ASCT-2 blocker used for inhibition of tumor growth.The metabolic alterations in tumors make it possible to visualize the latter by means of positron emission tomography, enabling diagnosis and providing metabolic information. The alanine serine cysteine transporter-2 (ASCT-2) is the main transporter of glutamine and is upregulated in several tumors. Therefore, a good positron emission tracer targeting this transport protein would have substantial value. Hence, the aim of this study is to develop a fluorine-18-labeled version of a V-9302 analogue, one of the most potent inhibitors of ASCT-2. The precursor was labeled with fluorine-18 via a nucleophilic substitution of the corresponding benzylic bromide. The cold reference product was subjected to in vitro assays with [3 H]glutamine in a PC-3 and F98 cell line to determine the affinity for both the human and rat ASCT-2. To evaluate the tracer potential dynamic μPET, images were acquired in a mouse xenograft model for prostate cancer. The tracer could be synthesized with an overall nondecay corrected yield of 3.66 ± 1.90%. in vitro experiments show inhibitor constants Ki of 90 and 125 μM for the PC-3 and F98 cells, respectively. The experiments in the PC-3 xenograft demonstrate a low uptake in the tumor tissue. We have successfully synthesized the radiotracer [18 F]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid. in vitro experiments show a good affinity for both the human and rat ASCT-2. However, the tracer suffers from poor in vivo tumor uptake in the PC-3 model. Briefly, we present the first fluorine-18-labeled derivative of compound V-9302, a promising novel ASCT-2 blocker used for inhibition of tumor growth.</description><issn>1099-1344</issn><issn>1099-1344</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqVUD1Pw0AMDQgkCnTgH3hMpabkS9DOiIoZsVdO6jauLudwvlSEX88FOiAxMVh-tp8_nqPoLksXWZrm9wdTu0WxfCjOo0mWrlZJVpTlxS98FV2rHtI0xGU5OZu-4pZFB-sbUtY5sIUjeyeAdgudI8MtW3QDVCxG9lyjATqi6dGzWJAdZEtY5wkGmiRlEsd5sCLZmV6cVGQ_BzOTj2F2gqdy_FNvyTch-Zf2PW5W9R6tcA1Y83YOCFaOZAANWrYESm509aCeRuAdWu3EeXKQByUNV-zFJRUqBTGiozAL1LLqeLyXVvYOu2YYW2tyt9HlDo3S9ORvonj9_Pb0knRO3ntSvwmtNZmwn6TXTV6myzy8fflY_IP6BXSkjNE</recordid><startdate>20200801</startdate><enddate>20200801</enddate><creator>Baguet, Tristan</creator><creator>Bouton, Jakob</creator><creator>Janssens, Jonas</creator><creator>Pauwelyn, Glenn</creator><creator>Verhoeven, Jeroen</creator><creator>Descamps, Benedicte</creator><creator>Van Calenbergh, Serge</creator><creator>Vanhove, Christian</creator><creator>De Vos, Filip</creator><scope>7X8</scope></search><sort><creationdate>20200801</creationdate><title>Radiosynthesis, in vitro and preliminary biological evaluation of 18 F2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid, a novel alanine serine cysteine transporter 2 inhibitor-based positron emission tomography tracer</title><author>Baguet, Tristan ; Bouton, Jakob ; Janssens, Jonas ; Pauwelyn, Glenn ; Verhoeven, Jeroen ; Descamps, Benedicte ; Van Calenbergh, Serge ; Vanhove, Christian ; De Vos, Filip</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_miscellaneous_24082002873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baguet, Tristan</creatorcontrib><creatorcontrib>Bouton, Jakob</creatorcontrib><creatorcontrib>Janssens, Jonas</creatorcontrib><creatorcontrib>Pauwelyn, Glenn</creatorcontrib><creatorcontrib>Verhoeven, Jeroen</creatorcontrib><creatorcontrib>Descamps, Benedicte</creatorcontrib><creatorcontrib>Van Calenbergh, Serge</creatorcontrib><creatorcontrib>Vanhove, Christian</creatorcontrib><creatorcontrib>De Vos, Filip</creatorcontrib><collection>MEDLINE - Academic</collection><jtitle>Journal of labelled compounds &amp; radiopharmaceuticals</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Baguet, Tristan</au><au>Bouton, Jakob</au><au>Janssens, Jonas</au><au>Pauwelyn, Glenn</au><au>Verhoeven, Jeroen</au><au>Descamps, Benedicte</au><au>Van Calenbergh, Serge</au><au>Vanhove, Christian</au><au>De Vos, Filip</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Radiosynthesis, in vitro and preliminary biological evaluation of 18 F2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid, a novel alanine serine cysteine transporter 2 inhibitor-based positron emission tomography tracer</atitle><jtitle>Journal of labelled compounds &amp; radiopharmaceuticals</jtitle><date>2020-08-01</date><risdate>2020</risdate><volume>63</volume><issue>10</issue><spage>442</spage><pages>442-</pages><issn>1099-1344</issn><eissn>1099-1344</eissn><abstract>The metabolic alterations in tumors make it possible to visualize the latter by means of positron emission tomography, enabling diagnosis and providing metabolic information. The alanine serine cysteine transporter-2 (ASCT-2) is the main transporter of glutamine and is upregulated in several tumors. Therefore, a good positron emission tracer targeting this transport protein would have substantial value. Hence, the aim of this study is to develop a fluorine-18-labeled version of a V-9302 analogue, one of the most potent inhibitors of ASCT-2. The precursor was labeled with fluorine-18 via a nucleophilic substitution of the corresponding benzylic bromide. The cold reference product was subjected to in vitro assays with [3 H]glutamine in a PC-3 and F98 cell line to determine the affinity for both the human and rat ASCT-2. To evaluate the tracer potential dynamic μPET, images were acquired in a mouse xenograft model for prostate cancer. The tracer could be synthesized with an overall nondecay corrected yield of 3.66 ± 1.90%. in vitro experiments show inhibitor constants Ki of 90 and 125 μM for the PC-3 and F98 cells, respectively. The experiments in the PC-3 xenograft demonstrate a low uptake in the tumor tissue. We have successfully synthesized the radiotracer [18 F]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid. in vitro experiments show a good affinity for both the human and rat ASCT-2. However, the tracer suffers from poor in vivo tumor uptake in the PC-3 model. Briefly, we present the first fluorine-18-labeled derivative of compound V-9302, a promising novel ASCT-2 blocker used for inhibition of tumor growth.The metabolic alterations in tumors make it possible to visualize the latter by means of positron emission tomography, enabling diagnosis and providing metabolic information. The alanine serine cysteine transporter-2 (ASCT-2) is the main transporter of glutamine and is upregulated in several tumors. Therefore, a good positron emission tracer targeting this transport protein would have substantial value. Hence, the aim of this study is to develop a fluorine-18-labeled version of a V-9302 analogue, one of the most potent inhibitors of ASCT-2. The precursor was labeled with fluorine-18 via a nucleophilic substitution of the corresponding benzylic bromide. The cold reference product was subjected to in vitro assays with [3 H]glutamine in a PC-3 and F98 cell line to determine the affinity for both the human and rat ASCT-2. To evaluate the tracer potential dynamic μPET, images were acquired in a mouse xenograft model for prostate cancer. The tracer could be synthesized with an overall nondecay corrected yield of 3.66 ± 1.90%. in vitro experiments show inhibitor constants Ki of 90 and 125 μM for the PC-3 and F98 cells, respectively. The experiments in the PC-3 xenograft demonstrate a low uptake in the tumor tissue. We have successfully synthesized the radiotracer [18 F]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid. in vitro experiments show a good affinity for both the human and rat ASCT-2. However, the tracer suffers from poor in vivo tumor uptake in the PC-3 model. Briefly, we present the first fluorine-18-labeled derivative of compound V-9302, a promising novel ASCT-2 blocker used for inhibition of tumor growth.</abstract><doi>10.1002/jlcr.3863</doi></addata></record>
fulltext fulltext
identifier ISSN: 1099-1344
ispartof Journal of labelled compounds & radiopharmaceuticals, 2020-08, Vol.63 (10), p.442
issn 1099-1344
1099-1344
language eng
recordid cdi_proquest_miscellaneous_2408200287
source Wiley-Blackwell Read & Publish Collection
title Radiosynthesis, in vitro and preliminary biological evaluation of 18 F2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid, a novel alanine serine cysteine transporter 2 inhibitor-based positron emission tomography tracer
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T02%3A07%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Radiosynthesis,%20in%20vitro%20and%20preliminary%20biological%20evaluation%20of%2018%20F2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic%20acid,%20a%20novel%20alanine%20serine%20cysteine%20transporter%202%20inhibitor-based%20positron%20emission%20tomography%20tracer&rft.jtitle=Journal%20of%20labelled%20compounds%20&%20radiopharmaceuticals&rft.au=Baguet,%20Tristan&rft.date=2020-08-01&rft.volume=63&rft.issue=10&rft.spage=442&rft.pages=442-&rft.issn=1099-1344&rft.eissn=1099-1344&rft_id=info:doi/10.1002/jlcr.3863&rft_dat=%3Cproquest%3E2408200287%3C/proquest%3E%3Cgrp_id%3Ecdi_FETCH-proquest_miscellaneous_24082002873%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2408200287&rft_id=info:pmid/&rfr_iscdi=true