@article{04021e806de445d89599fc9db909b5af,
title = "Synthesis and fluorine-18 radiolabeling of a phospholipid as a PET imaging agent for prostate cancer",
abstract = "Introduction: Altered 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. Methods: 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. Results: [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. Conclusions and advances in knowledge: 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.",
keywords = "Fluorine-18, Lipid metabolism, PET, Phospholipid, Prostate cancer",
author = "Kwan, {Kim H.} and Burvenich, {Ingrid J.G.} and Centenera, {Margaret M.} and Goh, {Yit Wooi} and Angela Rigopoulos and Jonas Dehairs and Swinnen, {Johannes V.} and Raj, {Ganesh V.} and Hoy, {Andrew J.} and Butler, {Lisa M.} and Scott, {Andrew M.} and White, {Jonathan M.} and Uwe Ackermann",
note = "Funding Information: We acknowledge the Australian Cancer Research Foundation for providing funds to purchase the nanoPET/MRI and nanoSPECT/CT imaging equipment. We utilized the services of the Simmons Cancer Center's Tissue Management Shared Resource at UT Southwestern Medical Center at Dallas. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number P30 CA142543 . This research was also undertaken using the Solid Target Laboratory, an ANSTO-Austin-LICR Partnership and with the support of the Operational Infrastructure Support Program of the Victorian State Government. We also acknowledge the use of the Melbourne Mass Spectrometry and Proteomics Facility (MMSPF) of the Bio21 Molecular Science and Biotechnology Institute at The University of Melbourne for the support of mass spectrometry analysis. AJH is supported by a Robinson Fellowship and funding from the University of Sydney . JVS is supported by the Research Foundation Flanders ( FWO G.0841.15 to JVS), the Stichting tegen Kanker (to JVS), KU Leuven ( C16/15/073 and C32/17/052 to JVS), Interreg V-A (EMR23 “EURLIPIDS”). LMB was supported by an Australian Research Council Future Fellowship (130101004), and a Beat Cancer SA Beat Cancer Project Principal Cancer Research Fellowship (PRF1117). AMS was supported by an NHRMC Senior Investigator grant ( 1177837 ). LMB, JVS, AS, and AJH are supported by the Movember Foundation and the Prostate Cancer Foundation of Australia ( MRTA3 ). GVR is supported by the Prostate Cancer Foundation (US) and the US Department of Defense . Funding Information: We acknowledge the Australian Cancer Research Foundation for providing funds to purchase the nanoPET/MRI and nanoSPECT/CT imaging equipment. We utilized the services of the Simmons Cancer Center's Tissue Management Shared Resource at UT Southwestern Medical Center at Dallas. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number P30 CA142543. This research was also undertaken using the Solid Target Laboratory, an ANSTO-Austin-LICR Partnership and with the support of the Operational Infrastructure Support Program of the Victorian State Government. We also acknowledge the use of the Melbourne Mass Spectrometry and Proteomics Facility (MMSPF) of the Bio21 Molecular Science and Biotechnology Institute at The University of Melbourne for the support of mass spectrometry analysis. AJH is supported by a Robinson Fellowship and funding from the University of Sydney. JVS is supported by the Research Foundation Flanders (FWO G.0841.15 to JVS), the Stichting tegen Kanker (to JVS), KU Leuven (C16/15/073 and C32/17/052 to JVS), Interreg V-A (EMR23 “EURLIPIDS”). LMB was supported by an Australian Research Council Future Fellowship (130101004), and a Beat Cancer SA Beat Cancer Project Principal Cancer Research Fellowship (PRF1117). AMS was supported by an NHRMC Senior Investigator grant (1177837). LMB, JVS, AS, and AJH are supported by the Movember Foundation and the Prostate Cancer Foundation of Australia (MRTA3). GVR is supported by the Prostate Cancer Foundation (US) and the US Department of Defense. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2021",
month = feb,
doi = "10.1016/j.nucmedbio.2020.11.007",
language = "English (US)",
volume = "93",
pages = "37--45",
journal = "Nuclear Medicine and Biology",
issn = "0969-8051",
publisher = "Elsevier Inc.",
}