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Objective: To label avidin (Av) or streptavidin (SA) with 153Sm by taking advantage of the high binding affinity of biotin to Av or SA. Methods: A biotin derivative (DTPA-biotin) was radiolabelled with 153Sm and then bound to Av or SA. The in vivo kinetics and biodistribution of 153Sm-labeled Ay, SA and DTPA-biotin were studied in rats and mice.Results: 153Sm-Av was characterized by rapid clearance from the blood with high liver and renal uptake; 153Sm-SA was cleared from the blood slowly with high retention in the liver, spleen and kidney, whereas 153Sm-DTPA-biotin metabolism was accelerated, and its excretion was mainly through the kidney. Conclusion: The biodistribution difference of SA and Av may provide an experimental basis for the selection of different components of avidin-biotin system in pretageting radioimmunoimaging and radioimmunotherapy.