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Radioimmunolocalization of Neuroblastoma Xenografts with Chimeric Antibody chCE7

Paul Scherrer Institute, Radiopharmacy Division, Villigen PSI, Switzerland
Central Laboratory of the Blood Transfusion Service of the Swiss Red Cross, Bern, Switzerland
Swiss Institute of Allergy and Asthma Research, Davos, Switzerland
Department of Nuclear Medicine, Inselspital, Bern, Switzerland

Correspondence: For reprints contact: Dr. P.A. Schubiger, Paul Scherrer Institute, Radiopharmacy Division, Villigen-PSI, Switzerland.

ABSTRACT

This study was performed to evaluate the tumor targeting ability of chCE7 with a view to clinical applications in neuroblastoma imaging and therapy. A chimeric (mouse/human) monoclonal antibody (chCE7) of gamma 1/kappa isotype directed against a neuroblastoma-associated cell-surface glycoprotein is described. In vitro chCE7 binds with high affinity (K_D 1 x 10^–10 M) to SKN-AS human neuroblastoma cells. Binding studies with ¹²⁵I-labeled chCE7 show temperature-dependent modulation of antigen binding and indicate that a proportion of the bound antibody is internalized due to rapid antigen turnover. In vivo biodistribution of radioiodinated chCE7 in nude mice bearing SKN-AS tumors shows optimal tumor uptake after 24 hr with about 30% of the injected dose per g. Optimal tumor/blood ratios (3.4:1) are reached after 4–5 days. Uptake in other organs including the reticuloendothelial system is low with tumor/organ ratios of 10 and more. Tumor uptake of chCE7 and the parent murine CE7 are found to be similar. Stability of chCE7 during and after radiolabeling is good with no loss of immunoreactivity in preparations labeled with ¹²³I up to 100 mCi/mg and 80% immunoreactivity after labeling with 13 mCi/mg of ¹³¹I. Neuroblastoma xenografts can be imaged by radioimmunoscintigraphy with ¹²³I-and ¹³¹I-labeled chCE7.

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