Radiation dosimetry results for zevalin radioimmunotherapy of rituximab-refractory non-hodgkin lymphoma

Authors

  • Gregory A. Wiseman M.D.,

    Corresponding author
    1. Division of Nuclear Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
    • Division of Nuclear Medicine, Mayo Clinic and Mayo Foundation, Charlton Building, 1-227, 200 First Street S.W., Rochester, MN 55905===

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  • Bryan Leigh M.D.,

    1. IDEC Pharmaceuticals Corporation, San Diego, California
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    • Bryan Leigh and Christine A. White are employees and stockholders of IDEC Pharmaceuticals Corporation; Dominick Lamonica, Daniel H. S. Silverman, and Ellen Kornmehl are consultants for IDEC; Richard Sparks is a former IDEC consultant; Ellen Kornmehl has received honoraria from IDEC for commissioned papers; Stewart M. Spies has received speaking honoraria and travel support from IDEC.

  • William D. Erwin M.S.,

    1. Department of Radiology, Northwestern University and Robert H. Lurie Cancer Center, Chicago, Illinois
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  • Dominick Lamonica M.D.,

    1. Department of Nuclear Medicine, Roswell Park Cancer Center, Buffalo, New York
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    • Bryan Leigh and Christine A. White are employees and stockholders of IDEC Pharmaceuticals Corporation; Dominick Lamonica, Daniel H. S. Silverman, and Ellen Kornmehl are consultants for IDEC; Richard Sparks is a former IDEC consultant; Ellen Kornmehl has received honoraria from IDEC for commissioned papers; Stewart M. Spies has received speaking honoraria and travel support from IDEC.

  • Ellen Kornmehl M.D.,

    1. Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts
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    • Bryan Leigh and Christine A. White are employees and stockholders of IDEC Pharmaceuticals Corporation; Dominick Lamonica, Daniel H. S. Silverman, and Ellen Kornmehl are consultants for IDEC; Richard Sparks is a former IDEC consultant; Ellen Kornmehl has received honoraria from IDEC for commissioned papers; Stewart M. Spies has received speaking honoraria and travel support from IDEC.

  • Stewart M. Spies M.D.,

    1. Department of Radiology, Northwestern University and Robert H. Lurie Cancer Center, Chicago, Illinois
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    • Bryan Leigh and Christine A. White are employees and stockholders of IDEC Pharmaceuticals Corporation; Dominick Lamonica, Daniel H. S. Silverman, and Ellen Kornmehl are consultants for IDEC; Richard Sparks is a former IDEC consultant; Ellen Kornmehl has received honoraria from IDEC for commissioned papers; Stewart M. Spies has received speaking honoraria and travel support from IDEC.

  • Daniel H. S. Silverman M.D.,

    1. Nuclear Medicine, Ahmanson Biochemical Imaging Center, UCLA Medical Center, Los Angeles, California
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    • Bryan Leigh and Christine A. White are employees and stockholders of IDEC Pharmaceuticals Corporation; Dominick Lamonica, Daniel H. S. Silverman, and Ellen Kornmehl are consultants for IDEC; Richard Sparks is a former IDEC consultant; Ellen Kornmehl has received honoraria from IDEC for commissioned papers; Stewart M. Spies has received speaking honoraria and travel support from IDEC.

  • Thomas E. Witzig M.D.,

    1. Division of Nuclear Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
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  • Richard B. Sparks Ph.D.,

    1. Oak Ridge Associated Universities, Oak Ridge, Tennessee
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    • Bryan Leigh and Christine A. White are employees and stockholders of IDEC Pharmaceuticals Corporation; Dominick Lamonica, Daniel H. S. Silverman, and Ellen Kornmehl are consultants for IDEC; Richard Sparks is a former IDEC consultant; Ellen Kornmehl has received honoraria from IDEC for commissioned papers; Stewart M. Spies has received speaking honoraria and travel support from IDEC.

  • Christine A. White M.D.

    1. IDEC Pharmaceuticals Corporation, San Diego, California
    Search for more papers by this author
    • Bryan Leigh and Christine A. White are employees and stockholders of IDEC Pharmaceuticals Corporation; Dominick Lamonica, Daniel H. S. Silverman, and Ellen Kornmehl are consultants for IDEC; Richard Sparks is a former IDEC consultant; Ellen Kornmehl has received honoraria from IDEC for commissioned papers; Stewart M. Spies has received speaking honoraria and travel support from IDEC.


Abstract

BACKGROUND

Zevalin consists of a murine anti-CD20 monoclonal antibody (ibritumomab) conjugated to the linker-chelator tiuxetan, which securely chelates indium-111 (111In) for imaging and dosimetry and yttrium-90 (90Y) for radioimmunotherapy (RIT). Previous trials involving rituximab-naïve patients have demonstrated excellent targeting of Zevalin to CD20+ B-cell non-Hodgkin lymphoma with minimal uptake in normal organs. The purpose of this trial was to perform 111In-Zevalin imaging in patients with rituximab-refractory tumors to determine normal organ dosimetry.

METHODS

Twenty-seven patients were given an imaging dose of 5 mCi (185 MBq) 111In-Zevalin on Day 0, evaluated with dosimetry, and then given a therapeutic dose of 0.4 mCi/kg (15 MBq/kg) 90Y-Zevalin on Day 7. Both Zevalin doses were preceded by an infusion of 250 mg/m2 rituximab to clear peripheral B cells and improve Zevalin biodistribution. Residence times for 90Y in blood and major organs were estimated from 111In biodistribution, and the MIRDOSE3 computer software program was used to calculate absorbed radiation doses to organs and red marrow.

RESULTS

Median estimated absorbed radiation doses from 90Y-Zevalin were 8.1 Gray (Gy) (range, 4.2–23.0 Gy) to the spleen, 5.1 Gy (range, 2.6–12.0 Gy) to the liver, 2.0 Gy (range, 1.4–5.3 Gy) to the lungs, 0.22 Gy (range, < 0.01–0.66 Gy) to the kidneys, and 0.74 Gy (range, 0.29–1.2 Gy) to the red marrow. These results are consistent with those from earlier Zevalin trials in rituximab-naïve patients. Hematologic toxicity was manageable and did not correlate with estimates of red marrow or total-body absorbed radiation dose.

CONCLUSIONS

Zevalin treatment of rituximab-refractory follicular NHL patients at 0.4 mCi/kg resulted in acceptable estimates of absorbed radiation dose to organs, similar to those observed in other Zevalin-treated populations. Cancer 2002;94:1349–57. © 2002 American Cancer Society.

DOI 10.1002/cncr.10305

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