Nuclear Medicine and Molecular Imaging Department, Azienda Ospedaliero-Universitaria di Parma, Italy.
Acta Biomed. 2020 Jul 6;91(4):e2020097. doi: 10.23750/abm.v91i4.9106.
Chemokine receptor-4 (CXCR4) is involved in tumor growth and progression in several types of human cancer. Recently, [68Ga]-DOTA-Pentixafor has been assessed as an excellent imaging probe targeting CXCR4-expression using positron emission tomography (PET). Here we report on the entire production cycle of [68Ga]-DOTA-Pentixafor, including quality control development and process validation.
Synthesis of [68Ga]-DOTA-Pentixafor was validated via three independent and consecutive production runs using an automated synthesis system. All validation runs must pass the pre-set quality control (QC) limits. Validation was performed for established QC tests to ensure that methods were reproducible and reliable in routine use. Germanium-68 breakthrough was determined for each sample. Production yield was calculated for each synthesis to assess the performance and efficiency of the radiolabeling process. The quality of the final product was determined by ITLC and HPLC methods after each synthesis.
The average ITLC-measured radiochemical purity was above 98.5% and HPLC-measured radiochemical purity was 99.86%, 99,83% and 100% in the three validation runs. Germanium breakthrough was 4.810-5%, 4.910-5% and 4.7*10-5% of total activity, far below the recommended level of 0.001%. Residual ethanol resulted 5.22%, 5.58% and 5.32%V/V; spot of HEPES impurity was not more intense than spot of reference solution (200µg/V). Endotoxin level resulted <17.5EU/ml. pH of the final product was 7 in all samples.
[68Ga]-DOTA-Pentixafor fit requirements of the pre-set quality parameters of purity, efficacy and safety in the batches considered for this study and fulfilled all the acceptance criteria for injectable radiopharmaceutical products. The results demonstrated a batch-to-batch reproducibility providing high radiochemical purity.
趋化因子受体-4（CXCR4）参与了多种人类癌症的肿瘤生长和进展。最近，[68Ga]-DOTA-Pentixafor 已被评估为一种针对 CXCR4 表达的优异的正电子发射断层扫描（PET）成像探针。在这里，我们报告了 [68Ga]-DOTA-Pentixafor 的整个生产周期，包括质量控制的开发和过程验证。
使用自动化合成系统进行了三次独立的连续生产运行，对 [68Ga]-DOTA-Pentixafor 的合成进行了验证。所有验证运行都必须通过预先设定的质量控制（QC）限制。验证是针对已建立的 QC 测试进行的，以确保方法在常规使用中具有可重复性和可靠性。对每个样品进行了锗-68 突破测试。为每个合成物计算了产率，以评估放射性标记过程的性能和效率。每次合成后，通过 ITLC 和 HPLC 方法确定最终产品的质量。
在三次验证运行中，平均 ITLC 测量的放射化学纯度均高于 98.5%，HPLC 测量的放射化学纯度分别为 99.86%、99.83%和 100%。锗突破分别为总活性的 4.810-5%、4.910-5%和 4.7*10-5%，远低于建议的 0.001%水平。残留乙醇分别为 5.22%、5.58%和 5.32%V/V；HEPES 杂质斑点的强度不比参比溶液（200µg/V）强。内毒素水平均<17.5EU/ml。所有样品的最终产品 pH 值均为 7。
在考虑的批次中，[68Ga]-DOTA-Pentixafor 符合纯度、功效和安全性的预设质量参数要求，并且满足了可注射放射性药物产品的所有验收标准。结果表明，批次间具有重现性，提供了高放射化学纯度。
