Pharmacokinetic modeling

For radiation dosimetry calculations of radiolabeled monoclonal antibodies, (MAB), pharmacokinetics are critical. Specifically, pharmacokinetic modeling is a useful component of estimation of cumulated activity in various source organs in the body. It is thus important to formulate general methods of pharmacokinetic modeling and of pharmacokinetic data reduction, leading to cumulated activities. In this paper different types of models are characterized as "empirical," "analytical," and "compartmental" pharmacokinetic models. There remains a pressing need for quantitative studies in man for a proper understanding of the pharmacokinetics of MAb. Pharmacokinetic modeling of radiolabeled MAb in vivo has relied on relatively limited studies in man and complementary detailed measurements in animals. In either case, any model chosen for analysis of such data is inevitably based on measurements of limited accuracy and precision as well as assumptions regarding human physiology. Very few macroscopic compartmental pharmacokinetic models for MAb, have been tested over a range of conditions to determine their predictive ability. Extracorporeal immunoadsorption represents one approach for drastically altering the biokinetics of antibody distribution, and may serve to validate a given pharmacokinetic model. In addition to macroscopic modeling, the microscopic evaluation of the time-dependent distribution of radiolabeled MAb in tissues is of utmost importance for a proper understanding of the kinetics and radiobiologic effect. Many tumors do not exhibit homogeneous uptake. A mathematical understanding of that distribution is thus essential for accurate tumor dosimetry estimates. This review summarizes methodologies for pharmacokinetic modeling, critically reviews specific pharmacokinetic models and demonstrates the capability of modeling for predictive calculations of altered pharmacokinetics, emphasizing its use in dosimetric calculations.