The partial volume effect (PVE) due to the low resolution of SPECT in brain SPECT volumes can be modeled as a convolution of a three-dimensional point-spread function (PSF) with the underlying true radioactivity. In this paper, a deconvolution guided by the edge locations in the geometric transfer matrix (GTM) method as a weighted regularization, denoted as RGTM, was proposed to take into account both the discrepancy from the convolution and the regional-homogeneity prior information in the correction of the PVE (PVC). Two steps were conducted: GTM and then a weighted regularization. Twenty digital phantom simulations were made to compare the performance of RGTM with those of Van-Cittert deconvolution (VC), GTM, and the region-based voxel-wise correction (RBV). Clinical data from eighty-four healthy adults with 99mTc-TRODAT-1 SPECT and MRI scans were also tested. Because the proposed RGTM was good in both constant and non-constant ROIs, its robustness is better than other methods if the distribution of the underlying radioactivity is not known exactly.