In this paper, a deformable registration method is proposed that enables automatic alignment of preoperative PET/CT to intraoperative ultrasound in order to achieve PET-determined focal prostate brachytherapy. Novel PET imaging agents such as prostate specific membrane antigen (PSMA) enables highly accurate identification of intra/extra-prostatic tumors. Incorporation of PSMA PET into the standard transrectal ultrasound (TRUS)-guided prostate brachytherapy will enable focal therapy, thus minimizing radiation toxicities. Our registration method requires PET/CT and TRUS volume as well as prostate segmentations. These input volumes are first rigidly registered by maximizing spatial overlap between the segmented prostate volumes, followed by the deformable registration. To achieve anatomically accurate deformable registration, we extract anatomical landmarks from both prostate boundary and inside the gland. Landmarks are extracted along the base-apex axes using two approaches: equiangular and equidistance. Three-dimensional thin-plate spline (TPS)-based deformable registration is then performed using the extracted landmarks as control points. Finally, the PET/CT images are deformed to the TRUS space by using the computed TPS transformation. The proposed method was validated on 10 prostate cancer patient datasets in which we registered post-implant CT to end-of-implantation TRUS. We computed target registration errors (TREs) by comparing the implanted seed positions (transformed CT seeds vs. intraoperatively identified TRUS seeds). The average TREs of the proposed method are 1.98±1.22 mm (mean±standard deviation) and 1.97±1.24 mm for equiangular and equidistance landmark extraction methods, respectively, which is better than or comparable to existing state-of-the-art methods while being computationally more efficient with an average computation time less than 40 seconds.