In vitro and in vivo pre-clinical analysis of a F(ab')(2) fragment of panitumumab for molecular imaging and therapy of HER1-positive cancers

Background: The objective of this study was to characterize the in vitro and in vivo properties of the F(ab')(2) fragment of panitumumab and to investigate its potential for imaging and radioimmunotherapy. Methods: The panitumumab F(ab')(2) was generated by enzymatic pepsin digestion. After the integrity and immunoreactivity of the F(ab')(2) was evaluated, the fragment was radiolabeled. In vivo studies included direct quantitation of tumor targeting and normal organ distribution of the radiolabeled panitumumab F(ab')(2) as well as planar gamma-scintigraphy and PET imaging. Results: The panitumumab F(ab')(2) was successfully produced by peptic digest. The F(ab')(2) was modified with the CHX-A-DTPA chelate and efficiently radiolabeled with either In-111 or Y-86. In vivo tumor targeting was achieved with acceptable uptake of radioactivity in the normal organs. The tumor targeting was validated by both imaging modalities with good visualization of the tumor at 24 h. Conclusions: The panitumumab F(ab')(2) fragment is a promising candidate for imaging of HER1-positive cancers.