In this study, tin fluoride colloid (SnF‐c) was prepared, labeled with yttrium‐90 (90Y), and characterized with respect to its physicochemical properties and biological behavior in an animal model. Particle size of SnF‐c, at constant concentration of SnF2, was dependent on pH, concentration of sodium fluoride (NaF), temperature, and time. The particle size of SnF‐c decreased with an increase in NaF concentration and a decrease in reaction mixture pH. Radiolabeling yield of 90Y–SnF‐c at higher temperature increased and it was greater than 98% for the preparation at 95°C. The 90Y–SnF‐c demonstrated high in vitro stability both in human serum and human synovial fluid at 37°C up to 7 days. In vivo distribution studies in healthy male Wistar rats of 90Y–SnF‐c (particles <1 μm), following intravenous administration, revealed that the localization takes place preferably in the liver. The 90Y–SnF‐c (particles >1 μm) was well retained in the synovial space for 96 h after intra‐articular injection, whereas leakage of 90Y from the joint was 1.96% over this period. Because of high labeling yield and stability, 90Y–SnF‐c might be a promising agent for radiosynovectomy or therapy of liver malignancies. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2194–2203, 2012