Yamaguchi Aiko, Hanaoka Hirofumi, Higuchi Tetsuya, Tsushima Yoshito
Bioimaging Information Analysis, Gunma University Graduate School of Medicine, Maebashi, Japan.
Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
J Labelled Comp Radiopharm. 2020 Jun 30;63(8):368-375. doi: 10.1002/jlcr.3840. Epub 2020 Apr 28.
L-2-[ F]fluoro-alpha-methylphenylalanine (2-[ F]FAMP) is a promising amino acid tracer for positron emission tomography (PET) imaging, yet the low production yield of direct electrophilic radiofluorination with [ F]F necessitates further optimization of the radiolabeling process. This paper describes a two-step preparation method for L-2-[ F]fluoro-alpha-methylphenylalanine (2-[ F]FAMP) starting from [ F]fluoride. The (Mesityl)(L-alpha-methylphenylalanine)-2-iodonium tetrafluoroborate precursors with various protecting groups were prepared. The copper-mediated F-fluorination of the iodonium salt precursors successfully produced 2-[ F]FAMP. The highest radio chemical conversion of 57.6% was noted with N-Piv-protected (mesityl)(aryl)iodonium salt in the presence of 5 equivalent of Cu (OTf) . Subsequent deprotection with 57% hydrogen iodide produced 2-[ F]FAMP within 120 min in 21.4 ± 11.7% overall radiochemical yield with >95% radiochemical purity and an enantiomeric excess >99%. The obtained 2-[ F]FAMP showed comparable biodistribution profiles in normal mice with that of the carrier-added 2-[ F]FAMP. These results indicate that usefulness of copper mediated F-fluorination for the production of 2-[ F]FAMP, which would facilitate clinical translation of the promising tumor specific amino acid tracer. Individual facilities could adopt either production method based on radioactivity demand and equipment availability.
L-2-[¹⁸F]氟-α-甲基苯丙氨酸(2-[¹⁸F]FAMP)是一种用于正电子发射断层扫描(PET)成像的有前景的氨基酸示踪剂,然而,用[¹⁸F]F进行直接亲电放射性氟化的低产率需要进一步优化放射性标记过程。本文描述了一种从[¹⁸F]氟化物开始制备L-2-[¹⁸F]氟-α-甲基苯丙氨酸(2-[¹⁸F]FAMP)的两步法。制备了具有各种保护基团的(均三甲苯基)(L-α-甲基苯丙氨酸)-2-碘鎓四氟硼酸盐前体。碘鎓盐前体的铜介导的¹⁸F-氟化成功地产生了2-[¹⁸F]FAMP。在5当量的Cu(OTf)₂存在下,N-Piv保护的(均三甲苯基)(芳基)碘鎓盐的最高放射化学转化率为57.6%。随后用57%的氢碘酸进行脱保护,在120分钟内产生2-[¹⁸F]FAMP,总放射化学产率为21.4±11.7%,放射化学纯度>95%,对映体过量>99%。所获得的2-[¹⁸F]FAMP在正常小鼠中的生物分布谱与添加载体的2-[¹⁸F]FAMP相当。这些结果表明铜介导的¹⁸F-氟化用于生产2-[¹⁸F]FAMP的实用性,这将促进这种有前景的肿瘤特异性氨基酸示踪剂的临床转化。各个机构可以根据放射性需求和设备可用性采用任何一种生产方法。