Department of Experimental Diagnosis Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Biomed Res Int. 2013;2013:460619. doi: 10.1155/2013/460619. Epub 2013 Jul 9.
Radiolabeled tyrosine analogs enter cancer cells via upregulated amino acid transporter system and have been shown to be superior to (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) in differential diagnosis in cancers. In this study, we synthesized O-[3-(19)F-fluoropropyl]-α-methyl tyrosine ((19)F-FPAMT) and used manual and automated methods to synthesize O-[3-(18)F-fluoropropyl]-α-methyl tyrosine ((18)F-FPAMT) in three steps: nucleophilic substitution, deprotection of butoxycarbonyl, and deesterification. Manual and automated synthesis methods produced (18)F-FPAMT with a radiochemical purity >96%. The decay-corrected yield of (18)F-FPAMT by manual synthesis was 34% at end-of-synthesis (88 min). The decay-corrected yield of (18)F-FPAMT by automated synthesis was 15% at end-of-synthesis (110 min). (18)F-FDG and (18)F-FPAMT were used for in vitro and in vivo studies to evaluate the feasibility of (18)F-FPAMT for imaging rat mesothelioma (IL-45). In vitro studies comparing (18)F-FPAMT with (18)F-FDG revealed that (18)F-FDG had higher uptake than that of (18)F-FPAMT, and the uptake ratio of (18)F-FPAMT reached the plateau after being incubated for 60 min. Biodistribution studies revealed that the accumulation of (18)F-FPAMT in the heart, lungs, thyroid, spleen, and brain was significantly lower than that of (18)F-FDG. There was poor bone uptake in (18)F-FPAMT for up to 3 hrs suggesting its in vivo stability. The imaging studies showed good visualization of tumors with (18)F-FPAMT. Together, these results suggest that (18)F-FPAMT can be successfully synthesized and has great potential in mesothelioma imaging.
放射性标记的酪氨酸类似物通过上调的氨基酸转运系统进入癌细胞，并已被证明在癌症的鉴别诊断中优于（18）F-氟代-2-脱氧-D-葡萄糖（（18）F-FDG）。在这项研究中，我们合成了 O-[3-（19）F-氟丙基]-α-甲基酪氨酸（（19）F-FPAMT），并使用手动和自动方法分三步合成 O-[3-（18）F-氟丙基]-α-甲基酪氨酸（（18）F-FPAMT）：亲核取代、脱除 Boc 保护基和脱酯化。手动和自动合成方法产生的（18）F-FPAMT 的放射化学纯度>96%。手动合成时（18）F-FPAMT 的放射性校正产率为终合成时的 34%（88 分钟）。自动合成时（18）F-FPAMT 的放射性校正产率为终合成时的 15%（110 分钟）。（18）F-FDG 和（18）F-FPAMT 用于体外和体内研究，以评估（18）F-FPAMT 用于成像大鼠间皮瘤（IL-45）的可行性。比较（18）F-FPAMT 与（18）F-FDG 的体外研究表明，（18）F-FDG 的摄取量高于（18）F-FPAMT，（18）F-FPAMT 的摄取比在孵育 60 分钟后达到平台期。生物分布研究表明，（18）F-FPAMT 在心脏、肺、甲状腺、脾脏和大脑中的积累明显低于（18）F-FDG。（18）F-FPAMT 骨骼摄取不良，高达 3 小时，表明其体内稳定性。成像研究显示（18）F-FPAMT 对肿瘤的良好可视化。综上所述，这些结果表明（18）F-FPAMT 可以成功合成，并具有间皮瘤成像的巨大潜力。
