The ibritumomab tiuxetan therapeutic regimen consists of a dose of rituximab, 250 mg/m(2), followed by In-111-ibritumomab tiuxetan, for imaging, on day 1 and a dose of rituximab followed by Y-90-ibritumomab tiuxetan, for therapy, on day 7, 8, or 9. Treatment with the Food and Drug Administration-approved regimen also requires that scans be performed at 2-24 h and at 48-72 In after the In-111-ibritumomab tiuxetan, with an optional third scan at 90-120 h, to confirm appropriate biodistribution. In the clinical trials before the approval of the regimen, only 1 patient (of approximately 400) was not treated with Y-90-ibritumomab tiuxetan after imaging with In-111-ibritumomab tiuxetan, because of altered biodistribution. The Zevalin Imaging Registry was established by Biogen Idec Inc. to identify cases of potential altered biodistribution and to collect clinical information in cases in which the regimen was not completed after imaging. Methods: The registry surveyed treating physicians to verify completion of treatment with the ibritumomab tiuxetan therapeutic regimen in patients treated with In-111-ibritumomab tiuxetan between March 27, 2002, and March 31, 2003. Results: Survey data were collected on 953 of an estimated 1,144-1,192 patients in whom ibritumomab tiuxetan therapy was initiated (case capture rate of 80%-83%). Thirty-eight cases were reported in which a decision not to treat was made after imaging with In-111-ibritumomab tiuxetan (4.0% of all cases captured); 16 of these were for imaging reasons, and 22 were for medical reasons. Twelve of the 16 imaging cases met the criteria for altered biodistribution (1.3%). Of these 12 cases, 6 (0.6%) were suspected to be true altered biodistribution and 6 appeared to be due to the use of a procedure for radiolabeling In-111-ibritumomab tiuxetan that differed from that in the prescribing information. All cases of altered biodistribution were seen on the first image (2-24 h) after the administration of In-111-ibritumomab tiuxetan. The 22 cases in which decisions not to treat were made for medical reasons accounted for 2.3% of the cases. The majority of these cases (19/22) were in patients who had an expected biodistribution but had a rapid change in their clinical condition that precluded treatment. Conclusion: The rate of true altered biodistribution was 0.6% in the Zevalin Imaging Registry, which collected treatment decisions based on data from approximately 80% of all patients treated commercially in the first year after drug approval. All cases of altered biodistribution were apparent on the first image, obtained at 2-24 h after the administration of In-111-ibritumomab tiuxetan.