Abstract | UNLABELLED: 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.
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Authors | D R Colnot, A J Wilhelm, J Cloos, J C Roos, R de Bree, J J Quak, G B Snow, G A van Dongen |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 42
Issue 9
Pg. 1364-7
(Sep 2001)
ISSN: 0161-5505 [Print] United States |
PMID | 11535726
(Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Radioisotopes
- Recombinant Fusion Proteins
- Rhenium
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Topics |
- Aged
- Algorithms
- Antibodies, Monoclonal
(adverse effects, immunology, pharmacokinetics, therapeutic use)
- Area Under Curve
- Bayes Theorem
- Bone Marrow
(radiation effects)
- Female
- Head and Neck Neoplasms
(radiotherapy)
- Humans
- Male
- Middle Aged
- Predictive Value of Tests
- Radioimmunotherapy
(adverse effects)
- Radioisotopes
(adverse effects, pharmacokinetics, therapeutic use)
- Radiotherapy Dosage
- Recombinant Fusion Proteins
- Regression Analysis
- Rhenium
(adverse effects, pharmacokinetics, therapeutic use)
- Thrombocytopenia
(etiology)
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