Synthesis and evaluation of 2-amino-5-(4-[18 F]fluorophenyl)pent-4-ynoic acid ([18 F]FPhPA): A novel18 F-labeled amino acid for oncologic PET imaging

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....

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Published in:Nuclear medicine and biology 2014, Vol.41 (8), p.660-669
Main Authors: Way, Jenilee D, Wang, Monica, Hamann, Ingrit, Wuest, Melinda, Wuest, Frank
Format: Article
Language:English
Subjects:
Radiology
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Summary: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 S onogashira 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. Conclusion L-[18 F]FPhPA is the first18 F-labeled amino acid prepared through Pd-mediated cross-coupling reaction. Advances in Knowledge and Implications for patient Care L-[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.
ISSN:0969-8051
1872-9614
DOI:10.1016/j.nucmedbio.2014.05.140