Microfluidic approach for fast labeling optimization and dose-on-demand implementation
Abstract Introduction The diffusion of PET as a pivotal molecular imaging modality has emphasized the need for new positron-emitting radiotracers to be used in diagnostic applications and research. Microfluidic represents an innovative approach, owing to its potential to increase radiochemical produ...
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| Veröffentlicht in: | Nuclear medicine and biology 2010-07, Vol.37 (5), p.547-555 |
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| creator | Pascali, Giancarlo Mazzone, Grazia Saccomanni, Giuseppe Manera, Clementina Salvadori, Piero A |
| description | Abstract Introduction The diffusion of PET as a pivotal molecular imaging modality has emphasized the need for new positron-emitting radiotracers to be used in diagnostic applications and research. Microfluidic represents an innovative approach, owing to its potential to increase radiochemical productivity in terms of yields, time reduction, precursor consumption and flexible experimental planning. Methods We focused on fluorine-18 labeling and used a microfluidic platform to perform sequential reactions, by using the same batch of18 F-labeling solution on one or more substrates, during the same experimental session. A solid-phase extraction (SPE) workup procedure was also implemented in the system to provide a repeatable purification step. Results We were able to quickly optimize the conditions for labeling of ethyl and propyl ditosylate and of a new cannabinoid type 2 (CB2) receptor agonist, CB41. In all substrates, we obtained good incorporation yields (60% to 85%) in short ( |
| doi_str_mv | 10.1016/j.nucmedbio.2010.03.006 |
| format | Article |
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Microfluidic represents an innovative approach, owing to its potential to increase radiochemical productivity in terms of yields, time reduction, precursor consumption and flexible experimental planning. Methods We focused on fluorine-18 labeling and used a microfluidic platform to perform sequential reactions, by using the same batch of18 F-labeling solution on one or more substrates, during the same experimental session. A solid-phase extraction (SPE) workup procedure was also implemented in the system to provide a repeatable purification step. Results We were able to quickly optimize the conditions for labeling of ethyl and propyl ditosylate and of a new cannabinoid type 2 (CB2) receptor agonist, CB41. In all substrates, we obtained good incorporation yields (60% to 85%) in short (<90 s) reaction times. Single dosages of the CB2 ligand were sequentially prepared, upon request, in satisfactory quantities and purity for small animal PET scanning. Conclusion This work demonstrates the usefulness of a microfluidic-based system for a rapid optimization of temperature, flow rate of reactants and their relative ratio in the labeling of different precursors by using the same18 F-fluoride batch. This approach was used to obtain in sequence several injectable doses of a novel CB2 ligand, thus providing the proof of principle that microfluidic systems permit a dose-on-demand production of new radiotracers.</description><identifier>ISSN: 0969-8051</identifier><identifier>EISSN: 1872-9614</identifier><identifier>DOI: 10.1016/j.nucmedbio.2010.03.006</identifier><identifier>PMID: 20610159</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Biological and medical sciences ; Cannabinoid ligand ; Cannabinoid Receptor Agonists ; Contrast media. Radiopharmaceuticals ; Cyclotrons ; Dose on demand ; Fluorine Radioisotopes - chemistry ; Fluoroalkyl synthon ; Isotope Labeling - instrumentation ; Isotope Labeling - methods ; Labeling optimization ; Ligands ; Medical sciences ; Microfluidic radiochemistry ; Microfluidics - instrumentation ; Microfluidics - methods ; Pharmacology. Drug treatments ; Positron-Emission Tomography ; Radiology ; Radiopharmaceuticals - chemistry ; Radiopharmaceuticals - pharmacology ; Time Factors</subject><ispartof>Nuclear medicine and biology, 2010-07, Vol.37 (5), p.547-555</ispartof><rights>Elsevier Inc.</rights><rights>2010 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright 2010 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c521t-f96345c7f686d91eb00168e41c25eff0cc9aa117e1dc8d341b0a7f9538b810c53</citedby><cites>FETCH-LOGICAL-c521t-f96345c7f686d91eb00168e41c25eff0cc9aa117e1dc8d341b0a7f9538b810c53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.nucmedbio.2010.03.006$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22995615$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20610159$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pascali, Giancarlo</creatorcontrib><creatorcontrib>Mazzone, Grazia</creatorcontrib><creatorcontrib>Saccomanni, Giuseppe</creatorcontrib><creatorcontrib>Manera, Clementina</creatorcontrib><creatorcontrib>Salvadori, Piero A</creatorcontrib><title>Microfluidic approach for fast labeling optimization and dose-on-demand implementation</title><title>Nuclear medicine and biology</title><addtitle>Nucl Med Biol</addtitle><description>Abstract Introduction The diffusion of PET as a pivotal molecular imaging modality has emphasized the need for new positron-emitting radiotracers to be used in diagnostic applications and research. Microfluidic represents an innovative approach, owing to its potential to increase radiochemical productivity in terms of yields, time reduction, precursor consumption and flexible experimental planning. Methods We focused on fluorine-18 labeling and used a microfluidic platform to perform sequential reactions, by using the same batch of18 F-labeling solution on one or more substrates, during the same experimental session. A solid-phase extraction (SPE) workup procedure was also implemented in the system to provide a repeatable purification step. Results We were able to quickly optimize the conditions for labeling of ethyl and propyl ditosylate and of a new cannabinoid type 2 (CB2) receptor agonist, CB41. In all substrates, we obtained good incorporation yields (60% to 85%) in short (<90 s) reaction times. Single dosages of the CB2 ligand were sequentially prepared, upon request, in satisfactory quantities and purity for small animal PET scanning. Conclusion This work demonstrates the usefulness of a microfluidic-based system for a rapid optimization of temperature, flow rate of reactants and their relative ratio in the labeling of different precursors by using the same18 F-fluoride batch. This approach was used to obtain in sequence several injectable doses of a novel CB2 ligand, thus providing the proof of principle that microfluidic systems permit a dose-on-demand production of new radiotracers.</description><subject>Biological and medical sciences</subject><subject>Cannabinoid ligand</subject><subject>Cannabinoid Receptor Agonists</subject><subject>Contrast media. Radiopharmaceuticals</subject><subject>Cyclotrons</subject><subject>Dose on demand</subject><subject>Fluorine Radioisotopes - chemistry</subject><subject>Fluoroalkyl synthon</subject><subject>Isotope Labeling - instrumentation</subject><subject>Isotope Labeling - methods</subject><subject>Labeling optimization</subject><subject>Ligands</subject><subject>Medical sciences</subject><subject>Microfluidic radiochemistry</subject><subject>Microfluidics - instrumentation</subject><subject>Microfluidics - methods</subject><subject>Pharmacology. Drug treatments</subject><subject>Positron-Emission Tomography</subject><subject>Radiology</subject><subject>Radiopharmaceuticals - chemistry</subject><subject>Radiopharmaceuticals - pharmacology</subject><subject>Time Factors</subject><issn>0969-8051</issn><issn>1872-9614</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkktv1TAQhS0EoreFvwDZIFa5zOThxBukqoKCVMSCx9Zy7DH4ktjBTpDKr8fhXorEipVl-5yZ48_D2FOEPQLyF4e9X_VEZnBhX0E-hXoPwO-xHfZdVQqOzX22A8FF2UOLZ-w8pQNkZ4PwkJ1VwHOZVuzY53dOx2DH1RmnCzXPMSj9tbAhFlalpRjVQKPzX4owL25yP9Xigi-UN4UJicrgS0PTtnXTPNJEfvmteMQeWDUmenxaL9in168-Xr0pb95fv726vCl1W-FSWsHrptWd5T03AmnYIvbUoK5asha0FkohdoRG96ZucADVWdHW_dAj6La-YM-PdXPu7yulRU4uaRpH5SmsSXZ1nVlgh1nZHZX5uSlFsnKOblLxViLIjak8yDumcmMqoZaZaXY-OfVYh3x95_sDMQuenQQqaTXaqLx26a-uEqLluIW9POooE_nhKMqkHXlNxkXSizTB_UeYl__U0Pl7XG77jW4pHcIafQYuUaZKgvywjcA2AQiw2Xn9C_Pdrtw</recordid><startdate>20100701</startdate><enddate>20100701</enddate><creator>Pascali, Giancarlo</creator><creator>Mazzone, Grazia</creator><creator>Saccomanni, Giuseppe</creator><creator>Manera, Clementina</creator><creator>Salvadori, Piero A</creator><general>Elsevier Inc</general><general>Elsevier</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>7X8</scope></search><sort><creationdate>20100701</creationdate><title>Microfluidic approach for fast labeling optimization and dose-on-demand implementation</title><author>Pascali, Giancarlo ; Mazzone, Grazia ; Saccomanni, Giuseppe ; Manera, Clementina ; Salvadori, Piero A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c521t-f96345c7f686d91eb00168e41c25eff0cc9aa117e1dc8d341b0a7f9538b810c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Biological and medical sciences</topic><topic>Cannabinoid ligand</topic><topic>Cannabinoid Receptor Agonists</topic><topic>Contrast media. Radiopharmaceuticals</topic><topic>Cyclotrons</topic><topic>Dose on demand</topic><topic>Fluorine Radioisotopes - chemistry</topic><topic>Fluoroalkyl synthon</topic><topic>Isotope Labeling - instrumentation</topic><topic>Isotope Labeling - methods</topic><topic>Labeling optimization</topic><topic>Ligands</topic><topic>Medical sciences</topic><topic>Microfluidic radiochemistry</topic><topic>Microfluidics - instrumentation</topic><topic>Microfluidics - methods</topic><topic>Pharmacology. Drug treatments</topic><topic>Positron-Emission Tomography</topic><topic>Radiology</topic><topic>Radiopharmaceuticals - chemistry</topic><topic>Radiopharmaceuticals - pharmacology</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pascali, Giancarlo</creatorcontrib><creatorcontrib>Mazzone, Grazia</creatorcontrib><creatorcontrib>Saccomanni, Giuseppe</creatorcontrib><creatorcontrib>Manera, Clementina</creatorcontrib><creatorcontrib>Salvadori, Piero A</creatorcontrib><collection>Pascal-Francis</collection><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>Nuclear medicine and biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pascali, Giancarlo</au><au>Mazzone, Grazia</au><au>Saccomanni, Giuseppe</au><au>Manera, Clementina</au><au>Salvadori, Piero A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Microfluidic approach for fast labeling optimization and dose-on-demand implementation</atitle><jtitle>Nuclear medicine and biology</jtitle><addtitle>Nucl Med Biol</addtitle><date>2010-07-01</date><risdate>2010</risdate><volume>37</volume><issue>5</issue><spage>547</spage><epage>555</epage><pages>547-555</pages><issn>0969-8051</issn><eissn>1872-9614</eissn><abstract>Abstract Introduction The diffusion of PET as a pivotal molecular imaging modality has emphasized the need for new positron-emitting radiotracers to be used in diagnostic applications and research. Microfluidic represents an innovative approach, owing to its potential to increase radiochemical productivity in terms of yields, time reduction, precursor consumption and flexible experimental planning. Methods We focused on fluorine-18 labeling and used a microfluidic platform to perform sequential reactions, by using the same batch of18 F-labeling solution on one or more substrates, during the same experimental session. A solid-phase extraction (SPE) workup procedure was also implemented in the system to provide a repeatable purification step. Results We were able to quickly optimize the conditions for labeling of ethyl and propyl ditosylate and of a new cannabinoid type 2 (CB2) receptor agonist, CB41. In all substrates, we obtained good incorporation yields (60% to 85%) in short (<90 s) reaction times. Single dosages of the CB2 ligand were sequentially prepared, upon request, in satisfactory quantities and purity for small animal PET scanning. Conclusion This work demonstrates the usefulness of a microfluidic-based system for a rapid optimization of temperature, flow rate of reactants and their relative ratio in the labeling of different precursors by using the same18 F-fluoride batch. This approach was used to obtain in sequence several injectable doses of a novel CB2 ligand, thus providing the proof of principle that microfluidic systems permit a dose-on-demand production of new radiotracers.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>20610159</pmid><doi>10.1016/j.nucmedbio.2010.03.006</doi><tpages>9</tpages></addata></record> |
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| subjects | Biological and medical sciences Cannabinoid ligand Cannabinoid Receptor Agonists Contrast media. Radiopharmaceuticals Cyclotrons Dose on demand Fluorine Radioisotopes - chemistry Fluoroalkyl synthon Isotope Labeling - instrumentation Isotope Labeling - methods Labeling optimization Ligands Medical sciences Microfluidic radiochemistry Microfluidics - instrumentation Microfluidics - methods Pharmacology. Drug treatments Positron-Emission Tomography Radiology Radiopharmaceuticals - chemistry Radiopharmaceuticals - pharmacology Time Factors |
| title | Microfluidic approach for fast labeling optimization and dose-on-demand implementation |
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