Radiosynthesis of [18F]-ethynyl-4-fluorobenzene for click conjugation

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dc.contributor.authorRoberts, MPen_AU
dc.contributor.authorPham, TQen_AU
dc.contributor.authorDoan, Jen_AU
dc.contributor.authorFraser, BHen_AU
dc.contributor.authorHambley, TWen_AU
dc.contributor.authorGreguric, Ien_AU
dc.date.accessioned2021-09-08T23:03:19Zen_AU
dc.date.available2021-09-08T23:03:19Zen_AU
dc.date.issued2013-05-09en_AU
dc.date.statistics2021-09-08en_AU
dc.descriptionVolume 56, Supplement 1 of the Journal of Labelled Compounds & Radiopharmaceuticals is comprised of the abstracts from the 20th International Symposium on Radiopharmaceutical Sciences.en_AU
dc.description.abstractObjectives: Fluorine-18 is the most commonly utilised PET nuclide due to its favourable characteristics including 110 min half-life, low positron energy and ease of availability. Unfavourable harsh reaction conditions required for direct labelling have led to the development of indirect labelling methods; including the use of the alkyne-azide copper(I) catalysed cycloaddition (CuAAC) ‘click’ reaction. We have investigated the one-step radiolabelling of a suitable precursor, 4-ethynyl-N,N,N-trimethylbenzenaminium triflate (1), particularly to probe the usefulness of the trimethylammonium leaving group, and developed a novel [18F]-alkynyl synthon (2) that has successfully been conjugated to an azido-sugar (3, R1) and azido-peptide mimetic (3, R2). Methods: Radiosynthesis (Figure 1) was achieved by reacting 4-ethynyl-N,N,N-trimethylbenzenaminium triflate (1) with activated K18F.K222 complex, in DMF at 150 °C for 5 minutes, via standard nucleophilic substitution, following HPLC purification to afford [18F]-ethynyl-4-fluorobenzene (2). The collected [18F]-synthon (2) was concentrated by passing through a reverse phase C18 Sep-Pak® Plus cartridge and then standard click reaction conditions were utilised by first eluting the [18F]-synthon with acetonitrile into a reaction vial containing copper(I) iodide, sodium ascorbate, lutidine and the azido derivative of choice in a water/acetonitrile mixture. The reaction was heated at 85 °C for 10 minutes and purified by HPLC to obtain the clicked derivative (3). FNNNNOTfF18H18FK222, K2CO3DMF, 150 °C,5 minazido-RCuINa-ascorbatelutidineACN/H2O 50%80 °C, 10 min18ROHNHOOHOHNONHR2=R1=OHOOHHOOH(1)(2)(3) Results: 4-Ethynyl-N,N,N-trimethylbenzenaminium triflate (1) was successfully labelled in 15-20% yield (non-decay corrected) after HPLC purification. In attempt to by-pass purification by HPLC a C18 Sep-Pak® was also attempted, however the decreased purity obtained resulted in decreased conjugation yields. The reasonably low yield of [18F]-ethynyl-4-fluorobenzene (2) is attributed to the competing [18]F-substitution on the trimethyl ammonium group forming [18F]-methylfluoride rather than the desired aromatic labelling. The alkynyl synthon (2) was successfully conjugated to 2 small molecules (a sugar and a peptide mimetic) using traditional CuAAC conditions. Conclusions: We have synthesised a new [18F]-labelled alkynyl synthon that was successfully clicked to two azido derivatives in adequate yield. Future work involves modification of the synthon with more activating substituents to decrease the competing [18F]-methylfluoride production and consequently increase the desired click conjugation yield. In addition we intend to further investigate other forms of cartridge purification. © 2013 John Wiley & Sons, Ltd.en_AU
dc.identifier.citationRoberts, M., Tien, P., Doan, J., Fraser, B., Hambley, T. & Greguric, I. (2013). Radiosynthesis of [F-18]-ethynyl-4-fluorobenzene for click conjugation. Poster presented at the 20th International Symposium on Radiopharmaceutical Sciences, Jeju, South Korea, May 12-17, 2013. In Journal of Labelled Compounds and Radiopharmaceuticals, 56, (S1), S178. doi:10.1002/jlcr.3058en_AU
dc.identifier.conferenceenddate17 May 2013en_AU
dc.identifier.conferencename20th International Symposium on Radiopharmaceutical Sciencesen_AU
dc.identifier.conferenceplaceJeju, South Koreaen_AU
dc.identifier.conferencestartdate12 May 2013en_AU
dc.identifier.issn1099-1344en_AU
dc.identifier.issueS1en_AU
dc.identifier.journaltitleJournal of Labelled Compounds and Radiopharmaceuticalsen_AU
dc.identifier.otherP-091en_AU
dc.identifier.paginationS178en_AU
dc.identifier.urihttps://doi.org/10.1002/jlcr.3058en_AU
dc.identifier.urihttps://apo.ansto.gov.au/dspace/handle/10238/11653en_AU
dc.identifier.volume56en_AU
dc.language.isoenen_AU
dc.publisherJohn Wiley & Sons, Incen_AU
dc.subjectSodiumen_AU
dc.subjectFluorine 18en_AU
dc.subjectCopper iodidesen_AU
dc.subjectAzido compoundsen_AU
dc.subjectPositron computed tomographyen_AU
dc.subjectLabellingen_AU
dc.titleRadiosynthesis of [18F]-ethynyl-4-fluorobenzene for click conjugationen_AU
dc.typeConference Posteren_AU
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