Background: Radiation synovectomy is an effective technique for the treatment of chronic synovitis in patients with rheumatoid arthritis (RA), and is an alternative for surgical synovectomy. Holmium ferric hydroxide macroaggregates (166Ho-FHMA) is suitable for radiation synovectomy, especially because it emits high-energy beta particles and a smaller proportion of low-energy photons that are suitable for gamma-camera imaging. Objective: The aim of this study was to develop a method to fuse 166Ho-FHMA single photon emission computed tomography (SPECT) and magnetic resonance (MRI) images, to show the distribution of 166Ho-FHMA inside the joint with images that localize synovitis. Methods: The knees of 6 patients with RA were treated with 166Ho-FHMA. 99mTc-human immunoglobulin (99mTc-HIG) SPECT images and MRI images were taken before 166Ho-FHMA injections. 166Ho-FHMA SPECT images were taken 4, 28, and 40 hours after injections. SPECT and MRI images were merged using a specific image fusion method, called mutual information algorithm, to study associations between anatomical and metabolic information from these images. Results: Fusion of SPECT and MRI images indicated that intensity of radioactivity was associated with the amount of synovitis. Activity distribution of 166Ho-FHMA could be registered using anatometabolic images. Conclusions: A new method to fuse the distribution of radiation in the synovectomy of the knee was developed using SPECT/MRI image registration. Image registration of SPECT and MRI can be used to determine the activity distribution of radioisotopes in relation to synovitis.