Development and characterization of 89Zr-labeled panitumumab for immuno-positron emission tomographic imaging of the epidermal growth factor receptor.
The epidermal growth factor receptor (EGFR) is overexpressed in the majority of malignancies and has been associated with poor outcomes. Panitumumab, an anti-EGFR monoclonal antibody that binds to the extracellular binding domain of EGFR, is increasingly used with radiotherapy and chemotherapy but has associated toxicities. The purpose of this study was to develop and characterize a novel targeted imaging agent for the EGFR using radiolabeled panitumumab. Flow cytometry studies were performed to evaluate EGFR expression in several cell lines. Desferrioxamine-Bz-NCS (DFO) was conjugated to panitumumab and labeled with (89)Zr. Cell uptake studies were performed in four cell lines. For biodistribution studies and micro-positron emission tomography/computed tomography (PET/CT), mouse xenograft models were generated using the same cell lines. PET was performed, and tumors and select organs were harvested for biodistribution studies. Panitumumab was radiolabeled with (89)Zr with high radiochemical purity and specific activity and was found to be stable in serum. Cell binding studies demonstrated that radiotracer uptake in cells correlated with the degree of EGFR expression. MicroPET/CT imaging studies demonstrated a high intensity of (89)Zr-panitumumab in A431 and HCT 116 tumors in comparison with the EGFR-negative tumors. Biodistribution studies confirmed the results from the imaging studies. (89)Zr-panitumumab imaging of EGFR-positive tumors demonstrated levels of radiotracer uptake associated with EGFR expression.
Department of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Albert J
AJ
Chang
Ravindra A
RA
De Silva
Suzanne E
SE
Lapi
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D004355:Drug Stability; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D064847:Multimodal Imaging; D000077544:Panitumumab; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D014183:Transplantation, Heterologous; D015040:Zirconium / Q000737:chemistry / Q000493:pharmacokinetics*
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D000077544:Panitumumab; D015040:Zirconium; C512478:EGFR protein, human; D066246:ErbB Receptors