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


CONCLUSIONS
Limited sampling seems useful to predict pharmacokinetics and myelotoxicity of 186Re-cMAb U36.
Colnot
D R
DR
Department of Otolaryngology/Head and Neck Surgery, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
Wilhelm
A J
AJ
Cloos
J
J
Roos
J C
JC
de Bree
R
R
Quak
J J
JJ
Snow
G B
GB
van Dongen
G A
GA
D000368:Aged; D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001499:Bayes Theorem; D001853:Bone Marrow / Q000528:radiation effects*; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016499:Radioimmunotherapy / Q000009:adverse effects*; D011868:Radioisotopes / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D011993:Recombinant Fusion Proteins; D012044:Regression Analysis; D012211:Rhenium / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000209:etiology
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D011993:Recombinant Fusion Proteins; D012211:Rhenium