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The influence of various factors on the biases affecting tumor-to-background activity ratio (TBR) estimates in positron emission tomography (PET) was studied using analytical simulations of an anthropomorphic phantom. The impact of attenuation correction (AC) on TBR as a function of tumor location and tumor-to-background density ratio was studied. The TBR changes that would be observed when a tumor with uniform uptake turns to a tumor with nonuniform uptake due a necrotic process were characterized. Major parameters affecting the bias in TBR estimates were the tumor diameter, the TBR, whether AC had been performed and the spatial resolution of the PET scanner. Our results suggest that a necrotic process gets detectable if the necrotic volume is at least 50% of the total tumor volume for a necrosis-to-tumor activity ratio of 0.5. We discuss how our results regarding TBR biases translate into standardized uptake values biases.