Abstract: Panitumumab (also known as ABX-EGF or Vectibix), is the first fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody that was approved by the FDA. Here we labeled Panitumumab with both ¹²⁵I and ¹¹¹In, and the in vitro and in vivo behaviors of ¹²⁵I and ¹¹¹In labeled Panitumumab were compared. Panitumumab was conjugated with the chelator DOTA for ¹¹¹In labeling and ¹²⁵I-Panitumumab was prepared by Iodogen method. The in vitro radioimmunoreactive fractions of ¹²⁵I/¹¹¹In-Panitumumab were determined on UM-SCC-22B head and neck cancer cells (EGFR-positive). Their in vivo biodistribution properties in normal mice were determined. ¹²⁵I or ¹¹¹In labeled Panitumumab can be prepared with high yield and high radiochemical purity, and both the two radiotracers possess excellent in vitro stability and high immunoreactivity. The uptake of ¹¹¹In labeled Panitumumab in liver and spleen is significantly higher than those of ¹²⁵I labeled Panitumumab as determined by biodistribution studies. Our data demonstrates that labeling with different radioisotopes may affect the in vitro and in vivo properties of biological molecules.