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Mathematical Model to Calculate the Total Number of Radiation Decays of Radiolabelled-Pembrolizumab in Mice

Immunotherapy with checkpoint inhibitors with Pembrolizumab shows potential to be used as a first-line in cancer treatment. A biodistribution study could be used to maximize efficacy and minimize the risk of the treatment. Therefore, it is necessary to describe the biodistribution of the 89Zr-Pembrolizumab. This study aims to create a mathematical model to explain how 89Zr-pembrolizumab is distributed in the body. Biodistribution data from Biokinetic data of 89Zr-Pembrolizumab in NSG mice engrafted with human lymphocyte peripheral (Hu-PBL-SCID) obtained from literature were used. The organ compartment of the model was divided into three sub-compartments: the vascular, interstitial, and endosomal space. The estimated parameters were the plasma clearance (CL), endocytosis modulation factors (F2), exocytosis modulation factors (F3) in the endosomal space, and modulation factors of the transcapillary flow (MK). According to the visualization of the fitted graphs and the percentage of variation (CV) of the fitted parameters (50%), the unknown parameters were successfully estimated with a goodness of fit method. The estimated value of CL was 2.65x10-5 l/h (CV=7.56%), parameter F2 was estimated for kidney, liver, spleen, and muscle tissue in the range of 0.12 - 0.35 (CV=4.14% - 5.60%), while F3 was estimated in the range of 3.60x10-3 - 0.036 (CV=2.21% - 21.44%), and the modulation factor of the transcapillary flow (MK) was within the range of 8.26 - 46.91 (CV=0.98% - 1.60%). A mathematical model was successfully used to describe the biodistribution of 89Zr-Pembrolizumab in mice.