Lee Sang Ju, Oh Seung Jun, Chi Dae Yoon, Kang Se Hun, Kil Hee Seup, Kim Jae Seung, Moon Dae Hyuk
Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, South Korea.
Nucl Med Biol. 2007 May;34(4):345-51. doi: 10.1016/j.nucmedbio.2007.02.007.
Although [18F] fluoropropylcarbomethoxyiodophenylnortropane (FP-CIT) is a promising radiopharmaceutical for dopamine transporter imaging, it has not been used for clinical studies because of low radiochemical yield. The purpose of our study was to develop a new radiochemistry method using a protic solvent system to obtain a high radiochemical yield of [18F]FP-CIT in single-step manual and automatic preparation procedures. [18F]F(-) was trapped on a QMA Sep-Pak cartridge or PS-HCO(3) cartridge and eluted with Cs2CO(3)/K222 buffer or TBAHCO3 respectively, or 8 microl of TBAOH was added directly to [18F]F(-)/H(2)(18)O solution in a reactor without using a cartridge. After drying, 18F] fluorination was performed with 2-6 mg of mesylate precursor, 100 microl of CH(3)CN and 500 microl of t-BuOH at 50-120 degrees C for 5-30 min, followed by high-performance liquid chromatography (HPLC) purification to obtain the final product. For comparison, the same procedure was performed with a tosylate precursor. Manual synthesis gave a decay-corrected radiochemical yield of 52.2+/-4.5%, and optimal synthesis conditions were as follows: TBAOH addition, 4 mg of precursor, 100 degrees C and 20 min of [18F] fluorination (n=3). We obtained low radiochemical yields of [18F]FP-CIT with carbonate elution systems such as Cs2CO(3) or TBAHCO3. We also developed an automatic synthesis method based on manual synthesis results. In automatic production, we obtained a decay-corrected radiochemical yield of 35.8+/-5.2% after HPLC purification, and we did not have any synthesis failures (n=14). Here, we describe our new method for the synthesis of [18F]FP-CIT using a protic solvent system. This method gave a high radiochemical yield with high reproducibility and might enable [18F]FP-CIT to be used clinically and commercially.
尽管[18F]氟丙基甲氧基碘苯基去甲托烷（FP-CIT）是一种用于多巴胺转运体成像的很有前景的放射性药物，但由于其放射化学产率较低，尚未用于临床研究。我们研究的目的是开发一种使用质子溶剂系统的新放射化学方法，以便在单步手动和自动制备过程中获得高放射化学产率的[18F]FP-CIT。[18F]F(-)被捕获在QMA Sep-Pak柱或PS-HCO(3)柱上，分别用Cs2CO(3)/K222缓冲液或TBAHCO3洗脱，或者将8微升TBAOH直接加入到反应器中的[18F]F(-)/H(2)(18)O溶液中，而不使用柱子。干燥后，在50-120℃下用2-6毫克甲磺酸盐前体、100微升CH(3)CN和500微升叔丁醇进行18F]氟化反应5-30分钟，然后通过高效液相色谱（HPLC）纯化以获得最终产物。为了进行比较，用对甲苯磺酸盐前体进行相同的操作。手动合成得到的衰变校正放射化学产率为52.2±4.5%，最佳合成条件如下：加入TBAOH、4毫克前体、100℃和20分钟的[18F]氟化反应（n=3）。我们用碳酸盐洗脱系统（如Cs2CO(3)或TBAHCO3）获得的[18F]FP-CIT放射化学产率较低。我们还根据手动合成结果开发了一种自动合成方法。在自动生产中，经过HPLC纯化后，我们获得的衰变校正放射化学产率为35.8±5.2%，并且没有任何合成失败的情况（n=14）。在此，我们描述了使用质子溶剂系统合成[18F]FP-CIT的新方法。该方法具有高放射化学产率和高重现性，可能使[18F]FP-CIT能够用于临床和商业用途。
