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

D. R. Colnot, A. J. Wilhelm, J. Cloos, J. C. Roos, R. De Bree, J. J. Quak, G. B. Snow, G. A M S Van Dongen

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Abstract

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.

Original languageEnglish
Pages (from-to)1364-1367
Number of pages4
JournalJournal of nuclear medicine
Volume42
Issue number9
Publication statusPublished - 27 Sept 2001

Keywords

  • Dosimetry
  • Limited sampling model
  • Monoclonal antibodies
  • Myelotoxicity
  • Pharmacokinetics
  • Radioimmunotherapy

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