Myeloablative ¹³¹I-Tositumomab Radioimmunotherapy in Treating Non-Hodgkin's Lymphoma: Comparison of Dosimetry Based on Whole-Body Retention and Dose to Critical Organ Receiving the Highest Dose

¹ Department of Radiology, University of Washington, Seattle, Washington
² Department of Medicine, University of Washington, Seattle, Washington
³ Pacific Northwest National Laboratory, Richland, Washington
⁴ Fred Hutchinson Cancer Research Center, Seattle, Washington

^* To whom correspondence should be addressed. E-mail: rajan{at}u.washington.edu.

	Abstract

Myeloablative radioimmunotherapy using ¹³¹I-tositumomab (anti-CD20) monoclonal antibodies is an effective therapy for B-cell non-Hodgkin's lymphoma. The amount of radioactivity for radioimmunotherapy may be determined by several methods, including those based on whole-body retention and on dose to a limiting normal organ. The goal of each approach is to deliver maximal myeloablative amounts of radioactivity within the tolerance of critical normal organs. Methods: Records of 100 consecutive patients who underwent biodistribution and dosimetry evaluation after tracer infusion of ¹³¹I-tositumomab before radioimmunotherapy were reviewed. We assessed organ and tissue activities over time by serial -camera imaging to calculate radiation-absorbed doses. Organ volumes were determined from CT scans for organ-specific dosimetry. These dose estimates helped us to determine therapy on the basis of projected dose to the critical normal organ receiving a maximum tolerable radiation dose. We compared organ-specific dosimetry for treatment planning with the whole-body dose-assessment method by retrospectively analyzing the differences in projected organ-absorbed doses and their ratios. Results: Mean organ doses per unit of administered activity (mGy/MBq) estimated by both methods were 0.33 for liver and 0.33 for lungs by the whole-body method and 1.52 for liver and 1.74 for lungs by the organ-specific method (P = 0.0001). The median differences between methods were 0.92 mGy/MBq (range, 0.36–2.2 mGy/MBq) for lungs, 0.82 mGy/MBq (range, 0.28–1.67 mGy/MBq) for liver, and –0.01 mGy/MBq (range, –0.18–0.16 mGy/MBq) for whole body. The median ratios of the treatment activities based on limiting normal-organ dose were 5.12 (range, 2.33–10.01) for lungs, 4.14 (range, 2.16–6.67) for liver, and 0.94 (range, 0.79–1.22) for whole body. We found substantial differences between the dose estimated by the 2 methods for liver and lungs (P = 0.0001). Conclusion: Dosimetry based on whole-body retention will underestimate the organ doses, and a preferable approach is to evaluate organ-specific doses by accounting for actual radionuclide biodistribution. Myeloablative treatments based on the latter approach allow administration of the maximum amount of radioactivity while minimizing toxicity.

Key Words: non-Hodgkin's lymphoma, radioimmunotherapy, internal dose, patient-specific dosimetry