Way Jenilee D, Wang Monica, Hamann Ingrit, Wuest Melinda, Wuest Frank
Department of Oncology, University of Alberta, 11560 University Ave, Edmonton AB, T6G 1Z2, Canada.
Department of Oncology, University of Alberta, 11560 University Ave, Edmonton AB, T6G 1Z2, Canada.
Nucl Med Biol. 2014 Sep;41(8):660-9. doi: 10.1016/j.nucmedbio.2014.05.140. Epub 2014 Jun 2.
(18)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.
(18)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.
(18)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.
L-[(18)F]FPhPA is the first (18)F-labeled amino acid prepared through Pd-mediated cross-coupling reaction.
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.
（18）F标记的氨基酸是用于癌症分子成像的重要正电子发射断层显像（PET）放射性示踪剂。本研究描述了2-氨基-5-（4-[(18)F]氟苯基）戊-4-炔酸（[(18)F]FPhPA）作为一种用于肿瘤成像的新型氨基酸放射性示踪剂的合成及放射性药物评价。
通过4-[(18)F]氟碘苯（[(18)F]FIB）与炔丙基甘氨酸之间的钯介导的Sonogashira交叉偶联反应制备[(18)F]FPhPA。使用小鼠乳腺癌细胞系EMT6，通过细胞摄取研究、放射性示踪剂摄取竞争抑制实验和小动物PET成像，与O-（2-[(18)F]氟乙基）-L-酪氨酸（[(18)F]FET）比较，评估[(18)F]FPhPA的放射性药物特性。
经半制备高效液相色谱（HPLC）纯化后，[(18)F]FPhPA的衰变校正放射性化学产率为42±10%，放射性化学纯度>95%。L-[(18)F]FPhPA在90分钟时细胞摄取量达到最大值，为58±14%放射性/毫克蛋白质。外消旋体和D-[(18)F]FPhPA的摄取量较低。合成氨基酸和天然氨基酸对放射性示踪剂摄取的抑制研究表明，Na(+)依赖性系统ASC，尤其是ASCT2，以及Na(+)非依赖性系统L是[(18)F]FPhPA进入EMT6细胞的重要氨基酸转运体。小动物PET研究表明，与[(18)F]FET相比，[(18)F]FPhPA在荷EMT6肿瘤小鼠中的肿瘤摄取同样较高，注射后60分钟时最大标准化摄取值（SUV）为1.35。与[(18)F]FET（SUV30分钟=0.40）相比，[(18)F]FPhPA在肌肉中的摄取较高（SUV30分钟=0.65），而与[(18)F]FET相比，[(18)F]FPhPA在脑中的摄取和清除更快。
L-[(18)F]FPhPA是通过钯介导的交叉偶联反应制备的首个（18）F标记的氨基酸。
L-[(18)F]FPhPA作为一种用于癌症中系统ASC和系统L氨基酸转运体分子成像的新型氨基酸放射性示踪剂，显示出有前景的特性。
