In targeted radionuclide therapy (TRT), dose estimation is essential for treatment planning and tumor dose response studies. Dose estimates are typically based on whole body conjugate view planar or SPECT imaging of the patient after administration of a planning dose. Quantifying the activity in the organs from these studies is an essential part of dose estimation. The Quantitative Planar (QPlanar) processing method involves both accurate compensation for image degrading factors and correction of overlap from background and organs. It thus provides more accurate activity estimates than traditional planar activity estimation methods. However, alignment between the 3D organ volume of interest (VOIs) used in QPlanar processing and the true organ projections in the planar images is required in this method. The goal of this research was to study the effects of mis-registration of VOIs on the accuracy and precision of organ activity estimates obtained using the QPlanar method. In this work, we modeled the degree of mis-registration that would be expected clinically. Mutual information based image registration was implemented to align realistic simulated 3D SPECT images that can be used to define 3D organ VOIs with 2D planar images. The resulting model of image mis-registration was applied to study the effects of mis-registration on the QPlanar method.