Preparation of clinical-grade (89) Zr-panitumumab as a positron emission tomography biomarker for evaluating epidermal growth factor receptor-targeted therapy.

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.