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High-Dose Radioimmunotherapy with ⁹⁰Y-Ibritumomab Tiuxetan: Comparative Dosimetric Study for Tailored Treatment

¹ Division of Medical Physics, European Institute of Oncology, Milan, Italy; ² Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy; ³ Division of Hematoncology, European Institute of Oncology, Milan, Italy; ⁴ Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee; and ⁵ Melanomas and Sarcomas Division, European Institute of Oncology, Milan, Italy

Correspondence: For correspondence or reprints contact: Giovanni Paganelli, MD, Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti, 435, 20141 Milan, Italy. E-mail: direzione.mnu{at}ieo.it

High-dose ⁹⁰Y-ibritumomab tiuxetan therapy and associated autologous stem cell transplantation (ASCT) were applied after dosimetry. This paper reports dosimetric findings for 3 different methods, including image corrections and actual organ mass corrections. Our first goal was to identify the most reliable and feasible dosimetric method to be adopted in high-dose therapy with ⁹⁰Y-ibritumomab tiuxetan. The second goal was to verify the safety of the prescribed activity and the best timing of stem cell reinfusion. Methods: Twenty-two patients with refractory non-Hodgkin's lymphoma were enrolled into 3 activity groups escalating to 55.5 MBq/kg. A somewhat arbitrary cutoff of 20 Gy to organs (except red marrow) was defined as a safe limit for patient recruitment. ASCT was considered of low risk when the dose to reinfused stem cells was less than 50 mGy. ¹¹¹In-Ibritumomab tiuxetan (185 MBq) was administered for dosimetry. Blood samples were collected up to 130 h after injection to derive individual blood clearance rates and red marrow doses. Five whole-body images were acquired up to 7 d after injection. A transmission scan and a low-dose CT scan were also acquired. The conjugate-view technique was used, and images were corrected for background, scatter, and attenuation. Absorbed doses were calculated using the OLINDA/EXM software, adjusting doses for individual organ masses. The biodistribution data were analyzed for dosimetry by the conjugate-view technique using 3 methods. Method A was a patient-specific method applying background, scatter, and attenuation correction, with absorbed doses calculated using the OLINDA/EXM software and doses adjusted for individual organ masses and individually estimated blood volumes. Method B was a reference method using the organ masses of the reference man and woman phantoms. Method C was a simplified method using standard blood and red marrow volumes and no corrections. Results: The medians and ranges (in parentheses) for dose estimates (mGy/MBq) according to method A were 1.7 (0.3–3.5) for lungs, 2.8 (1.8–10.6) for liver, 1.7 (0.6–3.8) for kidneys, 1.9 (0.8–5.0) for spleen, 0.8 (0.4–1.0) for red marrow, and 2.8 (1.3–4.7) for testes. None of patients had to postpone ASCT. Absorbed doses from method B differed from method A by up to 100% for liver, 80% for kidneys, 335% for spleen, and 80% for blood because of differences between standard and actual masses. Compared with method A, method C led to dose overestimates of up to 4-fold for lungs, 2-fold for liver, 5-fold for kidneys, 7-fold for spleen, 2-fold for red marrow, and 2-fold for testes. Conclusion: Patient-specific dosimetry with image correction and mass adjustment is recommended in high-dose ⁹⁰Y-ibritumomab tiuxetan therapy, for which liver is the dose-limiting organ. Overly simplified dosimetry may provide inaccurate information on the dose to critical organs, the recommended values of administered activity, and the timing of ASCT.

Key Words: high-dose Zevalin • patient-specific dosimetry • autologous stem cell transplantation • NHL • radioimmunotherapy

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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