Preclinical evaluation of a monoclonal antibody targeting the epidermal growth factor receptor as a radioimmunodiagnostic and radioimmunotherapeutic agent

Background and purpose: The studies described here are the first to evaluate the in vitro and in vivo properties of In-111-CHX-A '-panitumumab for radioimmunotherapy (alpha- and beta(-)-emitters) and radioimmunoimaging (single photon emission computed tomography and positron emission tomography). Experimental approach: Twenty-seven human carcinoma cell lines were analysed for expression of epidermal growth factor receptors by flow cytometry. Panitumumab was conjugated with CHX-A '-DTPA (diethylenetriamine-pentaacetic acid) and radiolabelled with In-111. Immunoreactivity of the CHX-A '-DTPA-panitumumab and In-111-CHX-A '-DTPA-panitumumab was evaluated by radioimmunoassays. Tumour targeting was determined in vivo by direct quantitation of tumour and normal tissues and by gamma-scintigraphy. Key results: For 26 of 27 human tumour cell lines, 95% of the cells expressed epidermal growth factor receptors over a range of intensity. Immunoreactivity of panitumumab was retained after modification with CHX-A '-DTPA. Radiolabelling of the immunoconjugate with In-111 was efficient with a specific activity of 19.5 +/- 8.9 mCi center dot mg(-1) obtained. Immunoreactivity and specificity of binding of the In-111-panitumumab was shown with A431 cells. Tumour targeting by In-111-panitumumab was demonstrated in athymic mice bearing A431, HT-29, LS-174T, SHAW or SKOV-3 s.c. xenografts with little uptake observed in normal tissues. The In-111-panitumumab was also evaluated in non-tumour-bearing mice. Pharmacokinetic studies compared the plasma retention time of the In-111-panitumumab in both non-tumour-bearing and A431 tumour-bearing mice. Tumour targeting was also visualized by gamma-scintigraphy. Conclusions and implications: Panitumumab can be efficiently radiolabelled with In-111 with high labelling yields. Based on the efficiency in tumour targeting and low normal tissue uptake, panitumumab may be an effective targeting component for radioimmunodiagnostic and radioimmunotherapeutic applications.