Positron emission tomography (PET) is a functional non-invasive imaging modality that uses radioactive substances (radiotracers) to measure changes in metabolic processes. Advances in scanner technology and data acquisition in the last decade have led to the development of more sophisticated PET devices with good spatial resolution (1–3 mm of full width at half maximum (FWHM)). However, there are involuntary motions produced by the patient inside the scanner that lead to image degradation and potentially to a misdiagnosis. The adverse effect of the motion in the reconstructed image increases as the spatial resolution of the current scanners continues improving. In order to correct this effect, motion correction techniques are becoming increasingly popular and further studied. This work presents a simulation study of an image motion correction using a frame-based algorithm. The method is able to cut the acquired data from the scanner in frames, taking into account the size of the object of study. This approach allows working with low statistical information without losing image quality. The frames are later registered using spatio-temporal registration developed in a multi-level way. To validate these results, several performance tests are applied to a set of simulated moving phantoms. The results obtained show that the method minimizes the intra-frame motion, improves the signal intensity over the background in comparison with other literature methods, produces excellent values of similarity with the ground-truth (static) image and is able to find a limit in the patient-injected dose when some prior knowledge of the lesion is present.