Voxel-based estimation of PET images, generally referred to as parametric imaging, can provide invaluable information about the heterogeneity of an imaging agent in a given tissue. Due to high level of noise in dynamic images, however, the estimated parametric image is often noisy and unreliable. Several approaches have been developed to address this challenge, including spatial noise reduction techniques, cluster analysis and spatial constrained weighted nonlinear least-square (SCWNLS) methods. In this study, we develop and test several noise reduction techniques combined with SCWNLS using simulated dynamic PET images. Both spatial smoothing filters and wavelet-based noise reduction techniques are investigated. In addition, 12 different parametric imaging methods are compared using simulated data. With the combination of noise reduction techniques and SCWNLS methods, more accurate parameter estimation can be achieved than with either of the two techniques alone. A less than 10% relative root-mean-square error is achieved with the combined approach in the simulation study. The wavelet denoising based approach is less sensitive to noise and provides more accurate parameter estimation at higher noise levels. Further evaluation of the proposed methods is performed using actual small animal PET datasets. We expect that the proposed method would be useful for cardiac, neurological and oncologic applications.