Synthesis of 225Ac-PSMA-617 for Preclinical Use
Synthesis of 225Ac-PSMA-617 for Preclinical Use
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DOI：
10.2174/1874471014666210709094616
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发表时间：
2022-01-01
影响因子：
2.3
通讯作者：
Scott, Peter James Henry
中科院分区：
文献类型：
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作者：
Dumond, Alexandra Rae Sowa;Rodnick, Melissa Elizabeth;Scott, Peter James Henry
背景：使用AC-225标记的放射性药物将放射性药物用于诊断和治疗的放射药物诊断和治疗是将核医学纳入核医学的新时代和α治疗时代。因此，需要可靠的AC-225-抗毒剂合成和质量控制的方法。目标：AC-225-PSMA-617用于前列腺癌患者的靶向α治疗，我们有可能合成药剂。用于临床前的使用。但是，由于缺乏有关合成和分析AC-225-radiotherapeics的信息的缺乏，技术转移被证明是繁琐的。为了满足这一需求，我们描述了AC-225-PSMA-617的直接合成以及使用现代宠物中心中标准设备的质量控制分析方法。游离水（0.67 mg/ml），并与500 mu L 0.05m Tris缓冲液合并，pH9。Actinium储备溶液（类似于65 MU CI加入15 mu l），并在120度C中加热反应40-50分钟。将反应冷却，并加入0.6 mL庆大酸溶液（4 mg/ml 0.2 m NH4OAC）。为了制定注射剂量，添加无菌盐水，USP（8 mL），并通过添加100 mu L 0.05 m Tris缓冲液（pH 9）来调整pH，以获得类似于7.2的最终pH。最终溶液使用0.22 MU M GV无菌过滤器过滤到无菌剂量小瓶中。通过Radio-TLC（洗脱液：50mm柠檬酸钠，pH 5）确定放射化学纯度，并使用AR2000扫描仪分析了板，并在高放射化学收益率（57 +/- 3 Mu CI，> 99％）和放射化学纯度（98 +/- 1％），用于临床前研究（9 mL，，， pH = 7.2），n = 3.结论：描述了AC-225-PSMA-617的直接合成，该合成将促进（前）临床研究的产生。该方法也可以适用于合成225AC的其他α半疗法。
Background: The recent approval of radiopharmaceuticals for diagnosis and treatment of cancer is ushering nuclear medicine into a new era of theranostics and alpha therapy using radiopharmaceuticals labeled with Ac-225 shows remarkable results in clinical trials. As such, reliable methods for the synthesis and quality control of Ac-225-radiopharmaceuticals are needed.Objective: Ac-225-PSMA-617 is being used for targeted alpha therapy in patients with prostate cancer, and we had cause to synthesize the agent for preclinical use. However, technology transfer proved cumbersome owing to the paucity of information available on synthesizing and analyzing Ac-225-radiotherapeutics. To address this need, we describe a straightforward synthesis of Ac-225-PSMA-617 as well as suitable approaches for quality control analysis using standard equipment in a modern PET Center.Methods: PSMA-617 precursor was dissolved in 25 mu L metal-free water (0.67 mg/mL) and combined with 500 mu L 0.05M Tris buffer, pH 9. Actinium stock solution (similar to 65 mu Ci in 15 mu L) was added and the reaction was heated at 120 degrees C for 40-50 min. The reaction was cooled and 0.6 mL gentisic acid solution (4 mg/mL in 0.2 M NH4OAc) was added. To formulate the dose for injection, sterile saline, USP (8 mL) was added and the pH was adjusted by the addition of 100 mu L 0.05 M Tris buffer (pH 9) to give a final pH of similar to 7.2. The final solution was filtered using a 0.22 mu m GV sterile filter into a sterile dose vial. Radiochemical purity was determined by radio-TLC (eluent: 50mM Sodium Citrate, pH 5), and plates were analyzed using an AR2000 scanner.Results: The method provided Ac-225-PSMA-617 in high radiochemical yield (57 +/- 3 mu Ci, >99%) and radiochemical purity (98 +/- 1%), formulated for preclinical studies (9 mL, pH = 7.2), n=3.Conclusion: A straightforward synthesis of Ac-225-PSMA-617 is described that will facilitate production for (pre)clinical studies. The approach could also be applicable to the synthesis of other alpha radiotherapeutics incorporating 225Ac.