MIRD Dose Estimate Report No. 20: Radiation Absorbed-Dose Estimates for 111In- and 90Y-Ibritumomab Tiuxetan

Absorbed-dose calculations provide a scientific basis for evaluating the biologic effects associated with administered radiopharmaceuticals. In cancer therapy, radiation dosimetry supports treatment planning, dose-response analyses, predictions of therapy effectiveness, and completeness of patient medical records. In this study, we evaluated the organ radiation absorbed doses from intravenously administered 111In- and 90Y-ibritumomab tiuxetan. Methods: Ten patients (6 men and 4 women) with non-Hodgkin lymphoma, cared for at 3 different medical centers, were administered the tracer 111In-ibritumomab tiuxetan and assessed using planar scintillation camera imaging at 5 time points and CT–organ volumetrics to determine patient-specific organ biokinetics and dosimetry. Explicit attenuation correction based on the transmission scan or transmission measurements provided the fraction of 111In-administered activity in 7 major organs, the whole body, and remainder tissues over time through complete decay. Time–activity curves were constructed, and radiation doses were calculated using MIRD methods and implementing software. Results: Mean radiation absorbed doses for 111In- and for 90Y-ibritumomab tiuxetan administered to 10 cancer patients are reported for 24 organs and the whole body. Biologic uptake and retention data are given for 7 major source organs, remainder tissues, and the whole body. Median absorbed dose values calculated by this method were compared with previously published dosimetry for ibritumomab tiuxetan and the product package insert. Conclusion: In high-dose radioimmunotherapy, the importance of patient-specific dosimetry becomes obvious when the objective of treatment planning is to achieve disease cures, safely, by limiting radiation dose to any critical normal organ to its maximum tolerable value. Compared with the current package insert, we found differences in median absorbed dose by multiples of 24 in the kidneys, 1.8 in the red marrow, 0.65 in the liver, 0.077 in the intestinal wall, 0.30 in the lungs, 0.46 in the spleen, and 0.34 in the heart wall.

[1]  D. Silverman,et al.  Radiation dosimetry results for zevalin radioimmunotherapy of rituximab‐refractory non‐hodgkin lymphoma , 2002, Cancer.

[2]  Daniel H. S. Silverman,et al.  Phase I/II 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin’s lymphoma , 2000, European Journal of Nuclear Medicine.

[3]  W. Nelp,et al.  Radiation absorbed dose from indium-111-CYT-356. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[4]  G. Denardo,et al.  Prediction of myelotoxicity using semi-quantitative marrow image scores. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[5]  S. Shen,et al.  Testicular uptake and radiation dose in patients receiving Zevalin and Pretarget CC49Fusion protein. , 2005, Cancer biotherapy & radiopharmaceuticals.

[6]  J G Kereiakes,et al.  In vivo quantitation of lesion radioactivity using external counting methods. , 1976, Medical physics.

[7]  M. Khazaeli Quantitation of mouse monoclonal antibody and human anti-mouse antibody response in serum of patients. , 1989, Hybridoma.

[8]  D. Podoloff,et al.  Radiation dosimetry results and safety correlations from 90Y-ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory non-Hodgkin's lymphoma: combined data from 4 clinical trials. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[9]  G. Wiseman,et al.  Additional radiation absorbed dose estimates for Zevalin radioimmunotherapy. , 2003, Cancer biotherapy & radiopharmaceuticals.

[10]  G. Martinelli,et al.  High-Dose Radioimmunotherapy with 90Y-Ibritumomab Tiuxetan: Comparative Dosimetric Study for Tailored Treatment , 2007, Journal of Nuclear Medicine.

[11]  Michael G Stabin,et al.  DECAY DATA FOR INTERNAL AND EXTERNAL DOSE ASSESSMENT , 2002, Health physics.

[12]  P. N. Badenhorst,et al.  Quantification of the distribution of 111In-labelled platelets in organs , 2004, European Journal of Nuclear Medicine.

[13]  S. Srivastava,et al.  Radiolabeled Monoclonal Antibodies for Imaging and Therapy , 1988, NATO ASI Series.

[14]  Hervé Watier,et al.  From the bench to the bedside: ways to improve rituximab efficacy. , 2004, Blood.

[15]  M. Prescott,et al.  Uptake, localization, and dosimetry of 111in and 201tl in human testes. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[16]  I. Buvat,et al.  Comparison between 2D and 3D dosimetry protocols in 90Y-ibritumomab tiuxetan radioimmunotherapy of patients with non-Hodgkin's lymphoma. , 2008, Cancer biotherapy & radiopharmaceuticals.

[17]  L. Taylor INTERNATIONAL COMMISSION ON RADIOLOGICAL UNITS AND MEASUREMENTS (ICRU) , 1966 .

[18]  Herbert Malamud,et al.  MIRD Primer for Absorbed Dose Calculations , 1989 .

[19]  P. Conti,et al.  The role of imaging with (111)In-ibritumomab tiuxetan in the ibritumomab tiuxetan (zevalin) regimen: results from a Zevalin Imaging Registry. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[20]  A. Brill,et al.  Radiation absorbed dose estimates for indium-111-labeled B72.3, an IgG antibody to ovarian and colorectal cancer: MIRD dose estimate report No. 18. , 1998, Journal of Nuclear Medicine.

[21]  G. Denardo,et al.  Quantitative Pharmacokinetics of Radiolabeled Monoclonal Antibodies for Imaging and Therapy in Patients , 1988 .

[22]  D. Podoloff,et al.  Radiation dosimetry results from a Phase II trial of ibritumomab tiuxetan (Zevalin) radioimmunotherapy for patients with non-Hodgkin's lymphoma and mild thrombocytopenia. , 2003, Cancer biotherapy & radiopharmaceuticals.

[23]  Michael G Stabin,et al.  OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[24]  F. Appelbaum,et al.  Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B cell lymphomas. , 1987, Blood.

[25]  J A Parker,et al.  Biodistribution and dosimetry results from a phase III prospectively randomized controlled trial of Zevalin radioimmunotherapy for low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. , 2001, Critical reviews in oncology/hematology.

[26]  S. Shen,et al.  Patient-specific dosimetry of pretargeted radioimmunotherapy using CC49 fusion protein in patients with gastrointestinal malignancies. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[27]  B. Wessels,et al.  MIRD pamphlet no. 16: Techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[28]  G Sgouros,et al.  Bone marrow dosimetry for radioimmunotherapy: theoretical considerations. , 1993, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[29]  J. Eary,et al.  Preliminary validation of the opposing view method for quantitative gamma camera imaging. , 1989, Medical physics.

[30]  I. Bernstein,et al.  Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support. , 1993, The New England journal of medicine.

[31]  W. S. Snyder,et al.  Report of the task group on reference man , 1979, Annals of the ICRP.