Population pharmacokinetics of antifibroblast activation protein monoclonal antibody F19 in cancer patients

Aims The population pharmacokinetics of I-131-mAbF19, a radiolabelled murin e monoclonal antibody against fibroblast activation protein and a potential antitumour stroma agent, were investigated during two phase I studies in c ancer patients. Methods I-131-mAbF19 serum concentration-time data were obtained in 16 pati ents from two studies involving imaging and dosimetry in colorectal carcino ma and soft tissue sarcoma. Doses of 0.2, 1 and 2 mg antibody were administ ered as 60 min intravenous infusions. The data were analysed by nonlinear m ixed effect modelling. Results The data were described by a two-compartment model. Population mean values were 109 ml h(-1) for total serum clearance, 3.1 l for the volume o f distribution of the central compartment, and 4.9 l for the volume of dist ribution at steady state. Mean terminal half-life was 38 h. Intersubject va riability was high, but no patient covariates could be identified that furt her explained this variability. In particular, there was no influence of tu mour type or mAbF19 dose. Conclusions The pharmacokinetics of antistromal mAbF19 were well defined in these two studies with different solid tumour types, and were comparable w ith those of other murine monoclonal antibodies that do not bind to normal tissue antigens or blood cells.