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Title: Synthesis and fluorine-18 radiolabeling of a phospholipid as a PET imaging agent for prostate cancer.
Austin Authors: Kwan, Kim H;Burvenich, Ingrid J G;Centenera, Margaret M;Goh, Yit Wooi;Rigopoulos, Angela;Dehairs, Jonas;Swinnen, Johannes V;Raj, Ganesh V;Hoy, Andrew J;Butler, Lisa M;Scott, Andrew M ;White, Jonathan M;Ackermann, Uwe 
Affiliation: School of Chemistry, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Australia
Department of Medicine, Melbourne University, Melbourne, Australia
Olivia Newton-John Cancer Research Institute
South Australian Health and Medical Research Institute, Adelaide, Australia
Adelaide Medical School and Freemasons Foundation Centre for Men's Health, University of Adelaide, Adelaide, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Australia
Laboratory of Lipid Metabolism and Cancer, Department of Oncology, LKI - Leuven Cancer Institute, KU Leuven - University of Leuven, Leuven, Belgium
Department of Urology, UT Southwestern Medical Center at Dallas, TX, USA
School of Medical Sciences, The University of Sydney, Sydney, Australia
Department of Pharmacology, UT Southwestern Medical Center at Dallas, TX, USA
School of Chemistry, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Australia
Molecular Imaging and Therapy
Issue Date: 28-Nov-2020
Date: 2020-11-28
Publication information: Nuclear Medicine and Biology 2020; 93: 37-45
Abstract: 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. 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.
DOI: 10.1016/j.nucmedbio.2020.11.007
Journal: Nuclear Medicine and Biology
PubMed URL: 33310350
Type: Journal Article
Subjects: Fluorine-18
Lipid metabolism
Prostate cancer
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