目的:使用市售专用[11C]-来自合成前体的化学模块,从市售起始材料和自动放射合成[11C]PiB有效合成前体。
背景:[11C]PiB是一种用于β-淀粉样蛋白PET成像的有前途的放射性示踪剂,推进阿尔茨海默病研究。有效放射性标记的前体和方案的可用性促进了任何放射性示踪剂的应用。以茴香胺和4-硝基苯甲酰氯为原料,分5步进行PiB前体的高效合成,有了加法,替换,和环化化学方法。该前体在市售的合成器中用于[11C]PiB的全自动放射合成。MPS-100(SHI,日本)。合成的[11C]PiB通过固相方法纯化,其质量控制是根据临床使用所需的质量和安全性标准进行的。
方法:用70-80%产率的市售材料开始合成所需的前体和标准的可信化合物。标准分析方法表征了所有合成的化合物。用于[11C]PiB与[11C]CH3OTf的放射合成的全自动[11C]化学合成仪(MPS-100)用作甲基化剂。对于放射性标记,探索了不同量的前体和反应时间。所得的粗产物通过固相柱进行纯化。合成的放射性示踪剂使用分析工具,如放射性TLC,HPLC,pH值内毒性,和半衰期。
结果:使用简单可行的化学方法以优异的产率获得了[11C]PiB的放射合成前体。使用自动合成仪开发了将前体放射性标记为合成的[11C]PiB的方案。粗放射性示踪剂通过固相柱纯化,衰变校正的放射化学产率为40±5%,放射化学纯度在约20分钟内超过97%(EOB)。计算比活性并发现在110-121mCi/μmol范围内。
结论:开发了一种可靠的方法来制备前体,然后使用[11C]MeOTf作为甲基化剂进行全自动放射性标记以合成[11C]PiB。最终的无HPLC纯化在一个放射性核素半衰期内产生超过97%的放射化学纯度示踪剂。该方法对于任何临床中心都是可重复和有效的。
OBJECTIVE: Efficient synthesis of precursor from commercially available starting materials and automated radiosynthesis of [11C]PiB using commercially available dedicated [11C]- Chemistry module from the synthesized precursor.
BACKGROUND: [11C]PiB is a promising radiotracer for PET imaging of β-Amyloid, advancing Alzheimer\'s disease research. The availability of precursors and protocols for efficient radiolabelling foster the applications of any radiotracer. Efficient synthesis of PiB precursor was performed using anisidine and 4-nitrobenzoyl chloride as starting materials in 5 steps, having addition, substitutions, and cyclization chemical methodologies. This precursor was used for fully automated radiosynthesis of [11C]PiB in a commercially available synthesizer, MPS-100 (SHI, Japan). The synthesized [11C]PiB was purified via solid-phase methodology, and its quality control was performed by the quality and safety criteria required for clinical use.
METHODS: The synthesis of desired precursors and standard authentic compounds started with commercially available materials with 70-80% yields. The standard analytical methods were characterized all synthesized compounds. The fully automated [11C]-chemistry synthesizer (MPS-100) used for radiosynthesis of [11C]PiB with [11C]CH3OTf acts as a methylating agent. For radiolabelling, varied amounts of precursor and time of reaction were explored. The resulting crude product underwent purification through solid-phase cartridges. The synthesized radiotracer was analyzed using analytical tools such as radio TLC, HPLC, pH endo-toxicity, and half-life.
RESULTS: The precursor for radiosynthesis of [11C]PiB was achieved in excellent yield using simple and feasible chemistry. A protocol for radiolabelling of precursor to synthesized [11C]PiB was developed using an automated synthesizer. The crude radiotracer was purified by solid-phase cartridge, with a decay-corrected radiochemical yield of 40±5% and radiochemical purity of more than 97% in approx 20 minutes (EOB). The specific activity was calculated and found in a 110-121 mCi/μmol range.
CONCLUSIONS: A reliable methodology was developed for preparing precursor followed by fully automated radiolabeling using [11C]MeOTf as a methylating agent to synthesize [11C]PiB. The final HPLC-free purification yielded more than 97% radiochemical purity tracer within one radionuclide half-life. The method was reproducible and efficient for any clinical center.