Pharmacokinetics of 111In-labelled monoclonal antibody ZCE-025 and fragments in tumour-bearing mice

Radiolabelled anti-tumor antibodies, their fragments and derivatives hold promise for imaging and therapeutics in oncology. A better understanding of the pharmacokinetcs of these entities is therefore important for clinical applications and management. In the present study, the in vivo behaviour of Indium-labelled monoclonal anti-CEA antibody ACE-025 and its F(ab’)2 and Fab’ fragments and a Fab‘ derivative are compared in the nude mouse-human tumour model. The object of the derivative was to improve the tumour uptake of the fragment yet reduce its high renal uptake while continuing to achieve desirable kinetics in the normal tissues. Uptake of the derivative in the tumour was comparable to that of the intact antibody and exceeded that of the underivatized fragments. Moreover, uptake in non-target tissues was lower with the derivative than with the intact entity. The renal uptake of the derivative was dramatically lower than for the fragments. The modelling data strongly suggest that the derivatives will be advantageous for clinical use compared with the underivatized whole antibodies or their fragments.