Wei Ling, Shi Jianfeng, Afari George, Bhattacharyya Sibaprasad
ADRD, SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
J Labelled Comp Radiopharm. 2014 Jan;57(1):25-35. doi: 10.1002/jlcr.3134. Epub 2013 Nov 13.
Panitumumab is a fully human monoclonal antibody approved for the treatment of epidermal growth factor receptor (EGFR) positive colorectal cancer. Recently, panitumumab has been radiolabeled with (89) Zr and evaluated for its potential to be used as immuno-positron emission tomography (PET) probe for EGFR positive cancers. Interesting preclinical results published by several groups of researchers have prompted us to develop a robust procedure for producing clinical-grade (89) Zr-panitumumab as an immuno-PET probe to evaluate EGFR-targeted therapy. In this process, clinical-grade panitumumab is bio-conjugated with desferrioxamine chelate and subsequently radiolabeled with (89) Zr resulting in high radiochemical yield (>70%, n = 3) and purity (>98%, n = 3). All quality control (QC) tests were performed according to United States Pharmacopeia specifications. QC tests showed that (89) Zr-panitumumab met all specifications for human injection. Herein, we describe a step-by-step method for the facile synthesis and QC tests of (89) Zr-panitumumab for medical use. The entire process of bioconjugation, radiolabeling, and all QC tests will take about 5 h. Because the synthesis is fully manual, two rapid, in-process QC tests have been introduced to make the procedure robust and error free.
帕尼单抗是一种全人源单克隆抗体，被批准用于治疗表皮生长因子受体（EGFR）阳性的结直肠癌。最近，帕尼单抗已用（89）Zr进行放射性标记，并评估了其作为EGFR阳性癌症免疫正电子发射断层扫描（PET）探针的潜力。几组研究人员发表的有趣的临床前结果促使我们开发一种稳健的程序，以生产临床级（89）Zr-帕尼单抗作为免疫PET探针，用于评估EGFR靶向治疗。在此过程中，临床级帕尼单抗与去铁胺螯合物进行生物共轭，随后用（89）Zr进行放射性标记，从而获得高放射化学产率（>70%，n = 3）和纯度（>98%，n = 3）。所有质量控制（QC）测试均按照美国药典规范进行。QC测试表明，（89）Zr-帕尼单抗符合人体注射的所有规范。在此，我们描述了一种用于医用（89）Zr-帕尼单抗简便合成和QC测试的分步方法。生物共轭、放射性标记的整个过程以及所有QC测试大约需要5小时。由于合成完全是手动操作，因此引入了两项快速的过程中QC测试，以使该程序稳健且无差错。
