Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/25893
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dc.contributor.authorKwan, Kim H-
dc.contributor.authorBurvenich, Ingrid J G-
dc.contributor.authorCentenera, Margaret M-
dc.contributor.authorGoh, Yit Wooi-
dc.contributor.authorRigopoulos, Angela-
dc.contributor.authorDehairs, Jonas-
dc.contributor.authorSwinnen, Johannes V-
dc.contributor.authorRaj, Ganesh V-
dc.contributor.authorHoy, Andrew J-
dc.contributor.authorButler, Lisa M-
dc.contributor.authorScott, Andrew M-
dc.contributor.authorWhite, Jonathan M-
dc.contributor.authorAckermann, Uwe-
dc.date2020-11-28-
dc.date.accessioned2021-02-21T22:47:52Z-
dc.date.available2021-02-21T22:47:52Z-
dc.date.issued2020-11-28-
dc.identifier.citationNuclear Medicine and Biology 2020; 93: 37-45en
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/25893-
dc.description.abstractAltered lipid metabolism and subsequent changes in cellular lipid composition have been observed in prostate cancer cells, are associated with poor clinical outcome, and are promising targets for metabolic therapies. This study reports for the first time on the synthesis of a phospholipid radiotracer based on the phospholipid 1,2-didocosahexaenoyl-sn-glycero-3-phosphocholine (PC44:12) to allow tracking of polyunsaturated lipid tumor uptake via PET imaging. This tracer may aid in the development of strategies to modulate response to therapies targeting lipid metabolism in prostate cancer. Lipidomics analysis of prostate tumor explants and LNCaP tumor cells were used to identify PC44:12 as a potential phospholipid candidate for radiotracer development. Synthesis of phosphocholine precursor and non-radioactive standard were optimised using click chemistry. The biodistribution of a fluorine-18 labeled analogue, N-{[4-(2-[18F]fluoroethyl)-2,3,4-triazol-1-yl]methyl}-1,2-didocosahexaenoyl-sn-glycero-3-phosphocholine ([18F]2) was determined in LNCaP prostate tumor-bearing NOD SCID gamma mice by ex vivo biodistribution and PET imaging studies and compared to biodistribution of [18F]fluoromethylcholine. [18F]2 was produced with a decay-corrected yield of 17.8 ± 3.7% and an average radiochemical purity of 97.00 ± 0.89% (n = 6). Molar activity was 85.1 ± 3.45 GBq/μmol (2300 ± 93 mCi/μmol) and the total synthesis time was 2 h. Ex vivo biodistribution data demonstrated high liver uptake (41.1 ± 9.2%ID/g) and high splenic uptake (10.9 ± 9.1%ID/g) 50 min post-injection. Ex vivo biodistribution showed low absolute tumor uptake of [18F]2 (0.8 ± 0.3%ID/g). However, dynamic PET imaging demonstrated an increase over time of the relative tumor-to-muscle ratio with a peak of 2.8 ± 0.5 reached 1 h post-injection. In contrast, dynamic PET of [18F]fluoromethylcholine demonstrated no increase in tumor-to-muscle ratios due to an increase in both tumor and muscle over time. Absolute uptake of [18F]fluoromethylcholine was higher and peaked at 60 min post injection (2.25 ± 0.29%ID/g) compared to [18F]2 (1.44 ± 0.06%ID/g) during the 1 h dynamic scan period. This study demonstrates the ability to radiolabel phospholipids and indicates the potential to monitor the in vivo distribution of phospholipids using fluorine-18 based PET.en
dc.language.isoeng
dc.subjectFluorine-18en
dc.subjectLipid metabolismen
dc.subjectPETen
dc.subjectPhospholipiden
dc.subjectProstate canceren
dc.titleSynthesis and fluorine-18 radiolabeling of a phospholipid as a PET imaging agent for prostate cancer.en
dc.typeJournal Articleen
dc.identifier.journaltitleNuclear Medicine and Biologyen
dc.identifier.affiliationSchool of Chemistry, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Australiaen
dc.identifier.affiliationOlivia Newton-John Cancer Research Instituteen
dc.identifier.affiliationDepartment of Medicine, Melbourne University, Melbourne, Australiaen
dc.identifier.affiliationSouth Australian Health and Medical Research Institute, Adelaide, Australiaen
dc.identifier.affiliationAdelaide Medical School and Freemasons Foundation Centre for Men's Health, University of Adelaide, Adelaide, Australiaen
dc.identifier.affiliationSchool of Cancer Medicine, La Trobe University, Melbourne, Australiaen
dc.identifier.affiliationLaboratory of Lipid Metabolism and Cancer, Department of Oncology, LKI - Leuven Cancer Institute, KU Leuven - University of Leuven, Leuven, Belgiumen
dc.identifier.affiliationDepartment of Urology, UT Southwestern Medical Center at Dallas, TX, USAen
dc.identifier.affiliationSchool of Medical Sciences, The University of Sydney, Sydney, Australiaen
dc.identifier.affiliationDepartment of Pharmacology, UT Southwestern Medical Center at Dallas, TX, USAen
dc.identifier.affiliationSchool of Chemistry, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Australiaen
dc.identifier.affiliationMolecular Imaging and Therapyen
dc.identifier.doi10.1016/j.nucmedbio.2020.11.007en
dc.type.contentTexten
dc.identifier.pubmedid33310350
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