Department of Nuclear Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Curr Radiopharm. 2024;17(3):302-311. doi: 10.2174/0118744710295705240229114137.
Efficient synthesis of precursor from commercially available starting materials and automated radiosynthesis of [C]PiB using commercially available dedicated [C]- Chemistry module from the synthesized precursor.
[C]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 [C]PiB in a commercially available synthesizer, MPS-100 (SHI, Japan). The synthesized [C]PiB was purified via solid-phase methodology, and its quality control was performed by the quality and safety criteria required for clinical use.
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 [C]-chemistry synthesizer (MPS-100) used for radiosynthesis of [C]PiB with [C]CHOTf 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.
The precursor for radiosynthesis of [C]PiB was achieved in excellent yield using simple and feasible chemistry. A protocol for radiolabelling of precursor to synthesized [C]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.
A reliable methodology was developed for preparing precursor followed by fully automated radiolabeling using [C]MeOTf as a methylating agent to synthesize [C]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.
从商业上可获得的起始材料高效合成前体，并使用商业上可获得的专用[C]化学模块从合成的前体自动化合成[C]PiB。
[C]PiB 是一种有前途的正电子发射断层扫描（PET）示踪剂，可用于β-淀粉样蛋白的成像，从而推进阿尔茨海默病的研究。前体和高效标记协议的可用性促进了任何示踪剂的应用。使用商业上可获得的合成器 MPS-100（SHI，日本），我们使用商业上可获得的邻茴香胺和 4-硝基苯甲酰氯作为起始材料，通过 5 步反应，采用加成、取代和环化化学方法，高效合成了 PiB 前体。该前体用于在商业上可获得的合成器 MPS-100 中全自动合成[C]PiB。合成的[C]PiB 通过固相方法进行纯化，其质量控制符合临床使用所需的质量和安全标准。
使用商业上可获得的材料，以 70-80%的收率开始合成所需的前体和标准纯品化合物。所有合成的化合物都采用标准分析方法进行了特征鉴定。用于用[C]CHOTf 作为甲基化试剂合成[C]PiB 的全自动[C]-化学合成器（MPS-100）。为了进行放射性标记，探索了不同的前体用量和反应时间。所得粗产物通过固相柱进行纯化。使用放射性薄层色谱法（radio TLC）、高效液相色谱法（HPLC）、pH 值内毒素和半衰期等分析工具分析合成的放射性示踪剂。
使用简单可行的化学方法，以优异的收率获得了用于[C]PiB 放射性合成的前体。使用自动化合成器开发了用于放射性标记前体以合成[C]PiB 的方案。粗放射性示踪剂通过固相柱进行纯化，在 EOB 时的放射性化学产率为 40±5%，放射性纯度大于 97%。放射性比活度进行了计算，发现范围在 110-121mCi/μmol 之间。
开发了一种可靠的方法，用于制备前体，然后使用[C]MeOTf 作为甲基化试剂进行全自动放射性标记，以合成[C]PiB。最后通过无高效液相色谱法的纯化，在一个放射性核素半衰期内获得放射性纯度大于 97%的示踪剂。该方法可重现且对任何临床中心都有效。
