Performance of a 62Zn/62Cu generator in clinical trials of PET perfusion agent 62Cu-PTSM.
Performance of a 62Zn/62Cu generator in clinical trials of PET perfusion agent 62Cu-PTSM.
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发表时间：
2000-02
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通讯作者：
N. Haynes;J. Lacy;N. Nayak;C. S. Martin;D. Dai;C. J. Mathias;M. Green
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作者：
N. Haynes;J. Lacy;N. Nayak;C. S. Martin;D. Dai;C. J. Mathias;M. Green
62Zn/62Cu PET发生器可以在典型的良好生产规范指导下从单个生产现场廉价生产和分发。因此，它有潜力极大地促进临床实用PET的发展。我们在一项研究中报告了发生器的性能，该研究比较了62cu - pyruvaldede -bis（n4-methylthiosemicarbazone (PTSM)）心肌灌注成像与99mTc-sestamibi在冠状动脉疾病诊断中的作用。62Zn/62Cu发生器是先前报道的采用62Cu- ptsm自动合成系统的改进版本。通过这种方法，消除了繁琐的18C纯化步骤。方法用质子轰击天然铜制备62Zn（半衰期9.3 h）母同位素。以37.5微A/h辐照的典型目标在要处理的当天中午12点交付。纯化后的62Zn以2mol /L的HCl装到生成柱上。发生器采用内部三通道蠕动泵洗脱，通过发生器柱输送2.25 mL洗脱液（1.8 mol/L NaCl, 0.2 mol/L HCl），在40 s内洗脱62Cu。同一泵同时泵入等量缓冲液（0.4 mol/L NaOAc）和1ml配体溶液（2ppm PTSM, 2% EtOH），通过隔膜将其送入预装28ml无菌水的35cc注射器中。该溶液通过注射器的搅拌彻底混合，并通过0.2微米的过滤器作为丸剂注射。发生器在运输前被洗脱两次，提供质量保证样品，并通过隔夜运输运送到临床现场。在发电机到达临床现场的前一天晚上进行了完整的质量保证测试。结果：共生产了34台发生器，并运送到2个临床站点，用于美国食品和药物管理局的III期研究。临床使用当天上午8:00发电机负荷活度为1.7+/-0.2 GBq (46.7+/-5.6 mCi)，产率为72%+/-16%。所有单位的高纯锗光谱均检测不到62Zn的突破。放射化学纯度为95.4%±2.4%。所有发电机的体积、pH值、无菌性和细菌内毒素测试均通过。发电机生产的整个过程，从目标接收到发电机发货，只用了不到6小时，成本约为1000美元，包括运费和回旋加速器成本。共68例患者注射2 62Cu-PTSM剂量，平均注射活性为0.8+/-0.2 GBq (20.5+/-5.3 mCi)，无不良副作用。结论62Zn/62Cu发生器是一种易于生产、可运输且价格低廉的PET放射性药物源，可以通过向与回旋加速器无关的部位提供放射性药物，扩大临床PET成像领域。
UNLABELLED The 62Zn/62Cu PET generator can be inexpensively produced and distributed from a single production site operating under typical good manufacturing practice guidelines. It therefore has the potential to greatly facilitate development of clinically practical PET. We report generator performance in a study in which 62Cu-pyruvaldehyde-bis(n4-methylthiosemicarbazone (PTSM) myocardial perfusion imaging is compared with 99mTc-sestamibi in the diagnosis of coronary artery disease. The 62Zn/62Cu generator is an improved version of a previously reported system that employs automated synthesis of 62Cu-PTSM. With this approach, the cumbersome step of 18C purification has been eliminated. METHODS The 62Zn (9.3 h half-life) parent isotope is prepared by proton bombardment of natural copper at 33 MeV. A typical target irradiated with 37.5 microA/h is delivered by 12:00 PM on the day it is to be processed. Purified 62Zn obtained from the target is loaded onto the generator column in 2 mol/L HCl. The generator is eluted using an internal three-channel peristaltic pump, which delivers 2.25 mL eluant (1.8 mol/L NaCl, 0.2 mol/L HCl) through the generator column to elute the 62Cu in 40 s. The same pump simultaneously pumps an equal volume of buffer (0.4 mol/L NaOAc) and 1 mL ligand solution (2 ppm PTSM, 2% EtOH) passing it through a septum into a 35-cc syringe preloaded with 28 mL sterile water. This solution is thoroughly mixed by agitation of the syringe and injected as a bolus through a 0.2 microm filter. The generator is eluted twice before shipping, providing quality assurance samples, and shipped to the clinical site by overnight delivery. Complete quality assurance testing is performed the evening before the generator reaches the clinical site. RESULTS A total of 34 generators have been produced and shipped to 2 clinical sites for a phase III Food and Drug Administration study. The load activity on the generators at 8:00 AM the day of clinical use was 1.7+/-0.2 GBq (46.7+/-5.6 mCi), and yield was 72%+/-16%. Breakthrough of 62Zn was undetectable by high-purity germanium spectroscopy for all units. Radiochemical purity was 95.4%+/-2.4%. Volume delivered, pH, sterility, and bacterial endotoxin tests yielded passing results on all generators. The entire process of generator production, from target receipt to generator shipment, took less than 6 h and cost approximately $1000, including shipping charges and cyclotron cost. A total of 68 patients were injected with 2 62Cu-PTSM doses, with a mean injected activity of 0.8+/-0.2 GBq (20.5+/-5.3 mCi) with no adverse side effects. CONCLUSION Results of this work confirm that the 62Zn/62Cu generator is an easily produced, transportable, and inexpensive source of PET radiopharmaceuticals, which can expand the field of clinical PET imaging by providing radiopharmaceuticals to sites not associated with cyclotrons.