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Evaluation of Limited Blood Sampling in a Preceding ^99mTc-Labeled Diagnostic Study to Predict the Pharmacokinetics and Myelotoxicity of ¹⁸⁶Re-cMAb U36 Radioimmunotherapy

Departments of Otolaryngology/Head and Neck Surgery and Nuclear Medicine, Vrije Universiteit Medical Center, Amsterdam, The Netherlands

¹⁸⁶Re-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 ^99mTc-labeled cMAb U36 before ¹⁸⁶Re-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 ¹⁸⁶Re-cMAb U36. Methods: Population pharmacokinetics of ¹⁸⁶Re-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: ¹⁸⁶Re-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 ¹⁸⁶Re-cMAb U36. These predictions were less accurate with ^99mTc-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 ^99mTc-cMAb U36 (r = 0.81, P < 0.01) or ¹⁸⁶Re-cMAb U36 (r = 0.79, P < 0.01). Conclusion: Limited sampling seems useful to predict pharmacokinetics and myelotoxicity of ¹⁸⁶Re-cMAb U36.

Key Words: radioimmunotherapy • monoclonal antibodies • pharmacokinetics • myelotoxicity • limited sampling model • dosimetry