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 ¹¹¹In-CHX-A″-panitumumab for radioimmunotherapy (α- and β^--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 ¹¹¹In. Immunoreactivity of the CHX-A″-DTPA-panitumumab and ¹¹¹In-CHX-A″-DTPA-panitumumab was evaluated by radioimmunoassays. Tumour targeting was determined in vivo by direct quantitation of tumour and normal tissues and by γ-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 ¹¹¹In was efficient with a specific activity of 19.5 ± 8.9 mCi·mg⁻¹ obtained. Immunoreactivity and specificity of binding of the ¹¹¹In-panitumumab was shown with A431 cells. Tumour targeting by ¹¹¹In-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 ¹¹¹In-panitumumab was also evaluated in non-tumour-bearing mice. Pharmacokinetic studies compared the plasma retention time of the ¹¹¹In-panitumumab in both non-tumour-bearing and A431 tumour-bearing mice. Tumour targeting was also visualized by γ-scintigraphy.

Conclusions and implications:

Panitumumab can be efficiently radiolabelled with ¹¹¹In 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.