Modeling and simulations of the pharmacokinetics of fluorophore conjugated antibodies in tumor vicinity for the optimization of fluorescence-based optical imaging.

摘要

BACKGROUND AND OBJECTIVES: One of the methods to detect and localize tumors in tissue is to use fluorophore conjugated specific antibodies as tumor surface markers. The goals of this study are to understand and quantify the pharmacokinetics of fluorophore conjugated antibodies in the vicinity of a tumor. This study concludes another stage of the development of a non-invasive fluorescenated antibody-based technique for imaging and localization of tumors in vivo. STUDY DESIGN/MATERIALS AND METHODS: A mathematical model of the pharmacokinetics of fluorophore conjugated antibodies in the vicinity of a tumor was developed based on histological staining experiments. We present the model equations of concentrations of antibodies and free binding sites. We also present a powerful simulation tool that we developed to simulate the imaging process. We analyzed the model and studied the effects of various independent parameters on the imaging result. These parameters included initial volume of markers (injected volume), total number of binding sites, tumor size, binding and dissociation rate constants, and the diffusion coefficient. We present the relations needed between these parameters in order to optimize the imaging results. RESULTS AND CONCLUSIONS: A powerful and accurate tool was developed which may assist in optimizing the imaging system results by setting the injection volume and concentration of fluorophore conjugated antibodies in tissue and approximating the time interval where maximum specific binding occurs and the tumor can be imaged.