Synthesis and evaluation of 2-amino-5-(4-[18F]fluorophenyl)pent-4-ynoic acid ([18F]FPhPA): A novel 18F-labeled amino acid for oncologic PET imaging |
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| Institution: | 1. Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, Shandong, China;2. Key Laboratory of Radiation Oncology of Shandong Province, Shandong Cancer Hospital and Institute, Jinan, Shandong, China;3. Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA;4. Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Jinan, Shandong, China;5. Department of Radiology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China;1. Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan;2. Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan;1. Laboratory for Radiopharmacy, KU Leuven, Belgium;2. MoSAIC, Molecular Small Animal Imaging Centre, KU Leuven, Belgium;3. Department of Nuclear Medicine & Molecular Imaging, University Medical Center Groningen, The Netherlands;4. Janssen Research & Development, Beerse, Belgium;5. Janssen Research & Development, Toledo, Spain;6. Division of Nuclear Medicine, KU Leuven and University Hospital Leuven, Belgium |
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| Abstract: | Introduction18 F-labeled amino acids are important PET radiotracers for molecular imaging of cancer. This study describes synthesis and radiopharmacological evaluation of 2-amino-5-(4-18 F]fluorophenyl)pent-4-ynoic acid (18 F]FPhPA) as a novel amino acid radiotracer for oncologic imaging.Methods18 F]FPhPA was prepared using Pd-mediated Sonogashira cross-coupling reaction between 4-18 F]fluoroiodobenzene (18 F]FIB) and propargylglycine. The radiopharmacological profile of 18 F]FPhPA was evaluated in comparison with O-(2-18 F]fluoroethyl)-L-tyrosine (18 F]FET) using the murine breast cancer cell line EMT6 involving cellular uptake studies, radiotracer uptake competitive inhibition experiments and small animal PET imaging.Results18 F]FPhPA was prepared in 42 ± 10% decay-corrected radiochemical yield with high radiochemical purity >95% after semi-preparative HPLC purification. Cellular uptake of L-18 F]FPhPA reached a maximum of 58 ± 14 % radioactivity/mg protein at 90 min. Lower uptake was observed for racemic and D-18 F]FPhPA.Radiotracer uptake inhibition studies by synthetic and naturally occurring amino acids suggested that Na+-dependent system ASC, especially ASCT2, and Na+-independent system L are important amino acid transporters for 18 F]FPhPA uptake into EMT6 cells. Small animal PET studies demonstrated similar high tumor uptake of 18 F]FPhPA in EMT6 tumor-bearing mice compared to 18 F]FET reaching a maximum standardized uptake value (SUV) of 1.35 after 60 min p.i.. Muscle uptake of 18 F]FPhPA was higher (SUV30min = 0.65) compared to 18 F]FET (SUV30min = 0.40), whereas 18 F]FPhPA showed a more rapid uptake and clearance from the brain compared to 18 F]FET.ConclusionL-18 F]FPhPA is the first 18 F-labeled amino acid prepared through Pd-mediated cross-coupling reaction.Advances in Knowledge and Implications for patient CareL-18 F]FPhPA displayed promising properties as a novel amino acid radiotracer for molecular imaging of system ASC and system L amino acid transporters in cancer. |
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