Biodistribution, radiation dosimetry and scouting of 90Y-ibritumomab tiuxetan therapy in patients with relapsed B-cell non-Hodgkin’s lymphoma using 89Zr-ibritumomab tiuxetan and PET

European Journal of Nuclear Medicine - 2012
Saiyada N. F. Rizvi1, Otto J. Visser2, Maria J. W. D. Vosjan3, Arthur van Lingen1, Otto S. Hoekstra1, Josée M. Zijlstra2, Peter C. Huijgens2, Guus A. M. S. van Dongen3, Mark Lubberink1,4
1Department of Nuclear Medicine and PET Research, VU University Medical Center Amsterdam, The Netherlands
2Department of Haematology, VU University Medical Center, Amsterdam, The Netherlands
3Department of Otolaryngology and Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands
4Department of Nuclear Medicine & PET, Uppsala University, and Medical Physics, Uppsala University Hospital, Uppsala, Sweden

Tóm tắt

Positron emission tomography (PET) with 89Zr-ibritumomab tiuxetan can be used to monitor biodistribution of 90Y-ibritumomab tiuxetan as shown in mice. The aim of this study was to assess biodistribution and radiation dosimetry of 90Y-ibritumomab tiuxetan in humans on the basis of 89Zr-ibritumomab tiuxetan imaging, to evaluate whether co-injection of a therapeutic amount of 90Y-ibritumomab tiuxetan influences biodistribution of 89Zr-ibritumomab tiuxetan and whether pre-therapy scout scans with 89Zr-ibritumomab tiuxetan can be used to predict biodistribution of 90Y-ibritumomab tiuxetan and the dose-limiting organ during therapy. Seven patients with relapsed B-cell non-Hodgkin’s lymphoma scheduled for autologous stem cell transplantation underwent PET scans at 1, 72 and 144 h after injection of ~70 MBq 89Zr-ibritumomab tiuxetan and again 2 weeks later after co-injection of 15 MBq/kg or 30 MBq/kg 90Y-ibritumomab tiuxetan. Volumes of interest were drawn over liver, kidneys, lungs, spleen and tumours. Ibritumomab tiuxetan organ absorbed doses were calculated using OLINDA. Red marrow dosimetry was based on blood samples. Absorbed doses to tumours were calculated using exponential fits to the measured data. The highest 90Y absorbed dose was observed in liver (3.2 ± 1.8 mGy/MBq) and spleen (2.9 ± 0.7 mGy/MBq) followed by kidneys and lungs. The red marrow dose was 0.52 ± 0.04 mGy/MBq, and the effective dose was 0.87 ± 0.14 mSv/MBq. Tumour absorbed doses ranged from 8.6 to 28.6 mGy/MBq. Correlation between predicted pre-therapy and therapy organ absorbed doses as based on 89Zr-ibritumomab tiuxetan images was high (Pearson correlation coefficient r = 0.97). No significant difference between pre-therapy and therapy tumour absorbed doses was found, but correlation was lower (r = 0.75). Biodistribution of 89Zr-ibritumomab tiuxetan is not influenced by simultaneous therapy with 90Y-ibritumomab tiuxetan, and 89Zr-ibritumomab tiuxetan scout scans can thus be used to predict biodistribution and dose-limiting organ during therapy. Absorbed doses to spleen were lower than those previously estimated using 111In-ibritumomab tiuxetan. The dose-limiting organ in patients undergoing stem cell transplantation is the liver.

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Tài liệu tham khảo

Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74–108.

Palanca-Wessels MC, Press OW. Improving the efficacy of radioimmunotherapy for non-Hodgkin lymphomas. Cancer 2010;116(4 Suppl):1126–33.

Gopal AK, Gooley TA, Golden JB, Maloney DG, Bensinger WI, Petersdorf SH, et al. Efficacy of high-dose therapy and autologous hematopoietic stem cell transplantation for non-Hodgkin’s lymphoma in adults 60 years of age and older. Bone Marrow Transplant 2001;27:593–9.

Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood 2005;105:1417–23.

Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2005;106:3725–32.

Herold M, Dölken G, Fiedler F, Franke A, Freund M, Helbig W, et al. Randomized phase III study for the treatment of advanced indolent non-Hodgkin’s lymphomas (NHL) and mantle cell lymphoma: chemotherapy versus chemotherapy plus rituximab. Ann Hematol 2003;82:77–9.

Kaminski MS, Tuck M, Estes J, Kolstad A, Ross CW, Zasadny K, et al. 131I-tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med 2005;352:441–9.

Winter JN. Combining yttrium 90-labeled ibritumomab tiuxetan with high-dose chemotherapy and stem cell support in patients with relapsed non-Hodgkin’s lymphoma. Clin Lymphoma 2004;5 Suppl 1:S22–6.

Nademanee A, Forman S, Molina A, Fung H, Smith D, Dagis A, et al. A phase 1/2 trial of high-dose yttrium-90-ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma. Blood 2005;106:2896–902.

Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, et al. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. J Clin Oncol 2002;20:2453–63.

Devizzi L, Guidetti A, Tarella C, Magni M, Matteucci P, Seregni E, et al. High-dose yttrium-90-ibritumomab tiuxetan with tandem stem-cell reinfusion: an outpatient preparative regimen for autologous hematopoietic cell transplantation. J Clin Oncol 2008;26:5175–82.

Ferrucci PF, Vanazzi A, Grana CM, Cremonesi M, Bartolomei M, Chinol M, et al. High activity 90Y-ibritumomab tiuxetan (Zevalin) with peripheral blood progenitor cells support in patients with refractory/resistant B-cell non-Hodgkin lymphomas. Br J Haematol 2007;139:590–9.

Wiseman GA, Leigh B, Erwin WD, Lamonica D, Kornmehl E, Spies SM, et al. Radiation dosimetry results for Zevalin radioimmunotherapy of rituximab-refractory non-Hodgkin lymphoma. Cancer 2002;94(4 Suppl):1349–57.

Fisher DR, Shen S, Meredith RF. MIRD dose estimate report No. 20: radiation absorbed-dose estimates for 111In- and 90Y-ibritumomab tiuxetan. J Nucl Med 2009;50:644–52.

Perk LR, Visser OJ, Stigter-van Walsum M, Vosjan MJ, Visser GW, Zijlstra JM, et al. Preparation and evaluation of (89)Zr-Zevalin for monitoring of (90)Y-Zevalin biodistribution with positron emission tomography. Eur J Nucl Med Mol Imaging 2006;33:1337–45.

Verel I, Visser GW, Boellaard R, Stigter-van Walsum M, Snow GB, van Dongen GA. 89Zr immuno-PET: comprehensive procedures for the production of 89Zr-labeled monoclonal antibodies. J Nucl Med 2003;44:1271–81.

Börjesson PK, Jauw YW, de Bree R, Roos JC, Castelijns JA, Leemans CR, et al. Radiation dosimetry of 89Zr-labeled chimeric monoclonal antibody U36 as used for immuno-PET in head and neck cancer patients. J Nucl Med 2009;50:1828–36.

Boellaard R, Hoekstra OS, Lammertsma AA. Software tools for standardized analysis of FDG whole body studies in multi-center trials [abstract]. J Nucl Med 2008;49 (Suppl 1):159P.

Wessels BW, Bolch WE, Bouchet LG, Breitz HB, Denardo GL, Meredith RF, et al. Bone marrow dosimetry using blood-based models for radiolabeled antibody therapy: a multiinstitutional comparison. J Nucl Med 2004;45:1725–33.

Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 2005;46:1023–7.

Shen S, Forero A, Meredith RF, Shah JJ, Knox SJ, Wiseman GA, et al. Impact of rituximab treatment on (90)Y- ibritumomab dosimetry for patients with non-Hodgkin lymphoma. J Nucl Med 2010;51:150–7.

Illidge TM, Bayne M, Brown NS, Chilton S, Cragg MS, Glennie MJ, et al. Phase 1/2 study of fractionated (131)I-rituximab in low-grade B-cell lymphoma: the effect of prior rituximab dosing and tumor burden on subsequent radioimmunotherapy. Blood 2009;113:1412–21.

Carrasquillo JA, White JD, Paik CH, Raubitschek A, Le N, Rotman M, et al. Similarities and differences in 111In- and 90Y-labeled 1B4M-DTPA antiTac monoclonal antibody distribution. J Nucl Med 1999;40:268–76.

Camera L, Kinuya S, Garmestani K, Brechbiel MW, Wu C, Pai LH, et al. Comparative biodistribution of indium- and yttrium-labeled B3 monoclonal antibody conjugated to either 2-(p-SCN-Bz)-6-methyl-DTPA (1B4M-DTPA) or 2-(p-SCN-Bz)-1,4,7,10-tetraazacyclododecane tetraacetic acid (2B-DOTA). Eur J Nucl Med 1994;21:640–6.

Garmestani K, Milenic DE, Plascjak PS, Brechbiel MW. A new and convenient method for purification of 86Y using a Sr(II) selective resin and comparison of biodistribution of 86Y and 111In labelled Herceptin. Nucl Med Biol 2002;29:599–606.

Perk LR, Visser GW, Vosjan MJ, Stigter-van Walsum M, Tijink BM, Leemans CR, et al. (89)Zr as a PET surrogate radioisotope for scouting biodistribution of the therapeutic radiometals (90)Y and (177)Lu in tumor-bearing nude mice after coupling to the internalizing antibody cetuximab. J Nucl Med 2005;46:1898–906.

Helisch A, Förster GJ, Reber H, Buchholz HG, Arnold R, Göke B, et al. Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2004;31:1386–92.

ICRP-41. Nonstochastic effects of ionizing radiation. Ann ICRP 1984;14:1–33.

Boellaard R, O’Doherty MJ, Weber WA, Mottaghy FM, Lonsdale MN, Stroobants SG, et al. FDG PET and PET/CT: EANM procedures guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging 2010;37:181–200.

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