RT Journal Article
SR Electronic
T1 Evaluation of Limited Blood Sampling in a Preceding <sup>99m</sup>Tc-Labeled Diagnostic Study to Predict the Pharmacokinetics and Myelotoxicity of <sup>186</sup>Re-cMAb U36 Radioimmunotherapy
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1364
OP 1367
VO 42
IS 9
A1 Colnot, David R.
A1 Wilhelm, Abraham J.
A1 Cloos, Jacqueline
A1 Roos, Jan C.
A1 de Bree, Remco
A1 Quak, Jasper J.
A1 Snow, Gordon B.
A1 van Dongen, Guus A.M.S.
YR 2001
UL http://jnm.snmjournals.org/content/42/9/1364.abstract
AB 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 &lt; 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 &lt; 0.01) or 186Re-cMAb U36 (r = 0.79, P &lt; 0.01). Conclusion: Limited sampling seems useful to predict pharmacokinetics and myelotoxicity of 186Re-cMAb U36.