Evaluation of limited blood sampling in a preceding Tc-99m-labeled diagnostic study to predict the pharmacokinetics and myelotoxicity of Re-186-cMAb U36 radioimmunotherapy

Re-186-labeled chimeric monoclonal antibody U36 (cMAb U36) was recently evaluated in a phase I dose escalation study in head and neck cancer patients. All 13 patients received Tc-99m-labeled cMAb U36 before Re-186-cMAb U36 radioimmunotherapy. The aim of this study was to evaluate the suitability of multiple or limited blood sampling to predict clearance, red marrow absorbed dose, and myelotoxicity of Re-186-cMAb U36. Methods: Population pharmacokinetics of Re-186-cMAb U36 were analyzed with a nonparametric expectation algorithm (NPEM 2) and used for Bayesian analysis of individual patient data to predict cMAb U36 clearance. Results: Re-186-cMAb U36 clearance was most accurately predicted (r = 0.91, P < 0.001) with limited sampling for sample points 4 and 72 h after administration of Re-186-cMAb U36. These predictions were less accurate with Tc-99m-cMAb U36 (r = 0.51, P = 0.078 for multiple sampling; r = 0.47, P = 0.104 for sampling at 4 and 21 h after administration), Thrombocytopenia was found to be correlated with the red marrow absorbed dose and was equally well predicted by limited blood sampling after administration of Tc-99m-cMAb U36 (r = 0.81, P < 0.01) or Re-186-cMAb U36 (r = 0.79, P < 0.01). Conclusion: Limited sampling seems useful to predict pharmacokinetics and myelotoxicity of Re-186-cMAb U36.