Segmentation of multidimensional dynamic positron emission tomography (PET) images into volumes of interest (VOIs) exhibiting similar temporal behavior and spatial features is a challenging task due to inherently poor signal-to-noise ratio and spatial resolution. In this study, we propose VOI segmentation of dynamic PET images by utilizing both the three-dimensional (3-D) spatial and temporal domain information in a hybrid technique that integrates two independent segmentation techniques of cluster analysis and region growing. The proposed technique starts with a cluster analysis that partitions the image based on temporal similarities. The resulting temporal partitions, together with the 3-D spatial information are utilized in the region growing segmentation. The technique was evaluated with dynamic 2-[18F] fluoro-2-deoxy-D-glucose PET simulations and clinical studies of the human brain and compared with the k-means and fuzzy c-means cluster analysis segmentation methods. The quantitative evaluation with simulated images demonstrated that the proposed technique can segment the dynamic PET images into VOIs of different kinetic structures and outperforms the cluster analysis approaches with notable improvements in the smoothness of the segmented VOIs with fewer disconnected or spurious segmentation clusters. In clinical studies, the hybrid technique was only superior to the other techniques in segmenting the white matter. In the gray matter segmentation, the other technique tended to perform slightly better than the hybrid technique, but the differences did not reach significance. The hybrid technique generally formed smoother VOIs with better separation of the background. Overall, the proposed technique demonstrated potential usefulness in the diagnosis and evaluation of dynamic PET neurological imaging studies.