Image-Based Assessment and Clinical Significance of Absorbed Radiation Dose to Tumor in Repeated High-Dose $^{131}I$ Anti-CD20 Monoclonal Antibody (Rituximab) Radioimmunotherapy for Non-Hodgkin's Lymphoma

반복적인 $^{131}I$ rituximab 방사면역치료를 시행 받은 비호지킨 림프종 환자 군에서 종양 부위의 영상기반 방사선 흡수선량 평가와 임상적 의의

  • Byun, Byung-Hyun (Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences) ;
  • Kim, Kyeong-Min (Lab. Of Nuclear Medicine Basic Research, Korea Institute of Radiological and Medical Sciences) ;
  • Woo, Sang-Keun (Lab. Of Nuclear Medicine Basic Research, Korea Institute of Radiological and Medical Sciences) ;
  • Choi, Tae-Hyun (Lab. Of Nuclear Medicine Basic Research, Korea Institute of Radiological and Medical Sciences) ;
  • Kang, Hye-Jin (Department of Internal Medicine, Korea Institute of Radiological and Medical Sciences) ;
  • Oh, Dong-Hyun (Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences) ;
  • Kim, Byeong-Il (Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences) ;
  • Cheon, Gi-Jeong (Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences) ;
  • Choi, Chang-Woon (Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences) ;
  • Lim, Sang-Moo (Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences)
  • Published : 2009.02.28

Abstract

Purpose: We assessed the absorbed dose to the tumor ($Dose_{tumor}$) by using pretreatment FDG-PET and whole-body (WB) planar images in repeated radioimmunotherapy (RIT) with $^{131}I$ rituximab for NHL. Materials and Methods: Patients with NHL (n=4) were administered a therapeutic dose of $^{131}I$ rituximab. Serial WB planar images alter RIT were acquired and overlaid to the coronal maximum intensity projection (MIP) PET image before RIT. On registered MIP PET and WB planar images, 2D-ROls were drawn on the region of tumor (n=7) and left medial thigh as background, and $Dose_{tumor}$ was calculated. The correlation between $Dose_{tumor}$ and the CT-based tumor volume change alter RIT was analyzed. The differences of $Dose_{tumor}$ and the tumor volume change according to the number of RIT were also assessed. Results: The values of absorbed dose were $397.7{\pm}646.2cGy$ ($53.0{\sim}2853.0cGy$). The values of CT-based tumor volume were $11.3{\pm}9.1\;cc$ ($2.9{\sim}34.2cc$), and the % changes of tumor volume before and alter RIT were $-29.8{\pm}44.3%$ ($-100.0%{\sim}+42.5%$), respectively. $Dose_{tumor}$ and the tumor volume change did not show the linear relationship (p>0.05). $Dose_{tumor}$ and the tumor volume change did not correlate with the number of repeated administration (p>0.05). Conclusion: We could determine the position and contour of viable tumor by MIP PET image. And, registration of PET and gamma camera images was possible to estimate the quantitative values of absorbed dose to tumor.

목적: 최근들어 비호지킨 림프종 환자군에서 $^{131}I$ 표지 rituximab을 이용한 반복적인 방사면역치료가 효과적인 치료방법임이 보고되고 있다. 이 연구에서는 $^{131}I$ 표지 rituximab을 이용하여 반복적인 방사면역치료를 시행받은 비호지킨 림프종 환자군에서 치료전 FDG-PET과 치료후 감마카메라를 이용한 전신 평면방출영상을 이용하여 종양의 흡수선량을 평가하였다. 대상 및 방법: 모두 4명의 환자들에게 치료용량의 $^{131}I$ 표지 rituximab ($7270.5{\pm}276.5MBq$)을 정맥주사하였다. 방사면역치료의 반복휫수는 3명에서는 3회, 1명에서는 4회였으며, 7개의 측정가능한 종양에 대해 총 21회의 평가가 이루어졌다. 감마카메라를 이용한 전신 평면방출영상을 방사면역치료 후 5분, 5시간, 24시간, 48시간 및 72시간에 연속적으로 촬영하였고, FDG PET/CT를 방사면역치료 전 1주일 이내와 방사면역치료 후 30일째 되는 날에 각각 촬영하였다. 방사면역치료 전 PET/CT로부터 관상면의 최대강도투사영상을 얻었고, 이 영상에 AMIDE소프트웨어를 이용하여 연속적인 전신 평면방출영상을 중첩시켰는데, 이 과정에서 4개의 해부학적 표지자(양측 어깨와 엉덩이)를 이용하였다. 중첩된 영상에서 종양부위와 왼쪽 안쪽 넓적다리(배경영역)의 관심영역을 그리고, 종양자체의 시간-방사능곡선을 구하였다. PET/CT에 포함된 CT영상으로부터 종양의 부피를 측정했으며, 각각의 종양부위의 SUVmax를 구하여 종양부피와 SUVmax의 방사면역 치료 전후 변화율을 평가하였다. 종양의 흡수선량과 부피변화율 간의 상관관계를 분석하였고, 방사면역치료 횟수에 따라서 종양의 흡수선량 및 부피 변화율에 유의한 차이가 있는지 알아보았다. 결과: 전체 환자군의 종양부위 흡수선량은 $397.7{\pm}646.2\;cGy$ ($53.0{\sim}2853.0\;cGy$)이었다. 방사면역 치료 전 종양의 부피는 $11.3{\pm}9.1\;cc$ ($2.9{\sim}34.2\;cc$)이었고, 치료 후 종양의 부피 변화율은 $-29.8{\pm}44.3%$($-100.0%{\sim}+42.5%$)이었다. 종양의 흡수선량과 부피 변화율 간에는 유의한 상관관계가 관찰되지 않았으며(p>0.05), 방사면역치료 횟수에 따라서 종양의 흡수선량 및 부피 변화율에도 유의한 차이가 관찰되지 않았다(p>0.05). 결론: FDG-PET의 최대강도투사영상을 이용하여 종양의 위치와 경계를 보다 명확하게 파악할 수 있었고, 감마카메라 영상과의 중첩을 통해서 효과적인 종양의 흡수선량평가가 가능하였다.

Keywords

References

  1. De Jong M, Kwekkeboom D, Valkema R, Krenning EP. Radiolabelled peptides for tumour therapy: current status and future directions-plenary lecture at the EANM 2002. Eur J Nucl Med Mol Imaging 2003;30:463-69 https://doi.org/10.1007/s00259-002-1107-8
  2. Bodei L, Cremonesi M, Grana C, Rocca P, Bartolomei M, Chinol M, Paganelli G. Receptor radionuclide therapy with $^{90}Y$-[DOTA]0-Tyr3-octreotide ($^{90}Y$-DOTATOC) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2004;31:1038-46
  3. Valkema R, Pauwels SA, Kvols LK, Kwekkeboom DJ, Jamar F, de Jong M, et al. Long-term follow-up of renal function after peptide receptor radiation therapy with $^{90}Y$-DOTATOC,Tyr3-octreotide and $^{177}$Lu-DOTA0,Tyr3-octreotate. J Nucl Med 2005;46(Suppl 1):83S-91S
  4. Kwekkeboom DJ, Mueller-Brand J, Paganelli G, Anthony LB, Pauwels S, Kvols LK, et al. An overview of the peptide receptor radionuclide therapy with 3 different radiolabeled somatostatin analogs. J Nucl Med 2005;46(Suppl 1):62S-6S
  5. Kwekkeboom DJ, Teunissen JJ, Bakker WH, Kooij PP, de Herder WW, Feelders RA. Radiolabeled somatostatin analog [$^{177}$LuDOTA0, Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J Gin Oncol 2005;23:2754-62 https://doi.org/10.1200/JCO.2005.08.066
  6. Virgolini I, Britton K, Buscornbe J, Moncayo R, Paganelli G, Riva P. In- and Y-DOTA-lanreotide: results and implications of the MAURITIUS trial. Semin Nucl Med 2002;32:148-55 https://doi.org/10.1053/snuc.2002.31565
  7. Reubi JC, Ma''ke HR, Krenning EP. Candidates for peptide receptor radiotherapy today and in the future. J Nucl Med 2005;46(Suppl 1):67S-75S
  8. Kaminski MS, Zelenetz AD, Press OW, Saleh M, Leonard J, Fehrenbacher L. Pivotal study of iodine $^{131}$I tositumomab for chemotherapy-refractory low-grade or transformed low grade B-cell non-Hodgkin's lymphomas. J Clin Oncol 2001;19:3918-28 https://doi.org/10.1200/JCO.2001.19.19.3918
  9. Kaminski MS, Tuck M, Estes J, Kolstad A, Ross CW, Zasadny K, et al. $^{131}$I tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med 2005;352:441-49 https://doi.org/10.1056/NEJMoa041511
  10. Wiseman GA, White CA, Stabin M, Dunn WL, Erwin W, Dahlbom M, et al. Phase I/II $^{90}$Y-Zevalin ($^{90}$Y-ibritwnomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin's lymphoma. Eur J Nucl Med 2000;27:766-77 https://doi.org/10.1007/s002590000276
  11. Witzig TE, Flinn IW, Gordon LI, Vo K, Wiseman GA, Flinn IW, et al. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory non-Hodgkin's lymphoma. J Clin Oncol 2002;20:3262-69 https://doi.org/10.1200/JCO.2002.11.017
  12. Bishton MJ, Leahy MF, Hicks RJ, Turner JH, McQuillan AD, Seymour JF. Repeat treatment with $^{131}$I rituximab is safe and effective in patients with relapsed indolent B-cell non-Hodgkin's lymphoma who had previously responded to $^{131}$I rituximab. Annals of Oncology 2008;19:1629-33 https://doi.org/10.1093/annonc/mdn172
  13. Kaminski MS, Radford JA, Gregory SA, Leonard JP, Knox SJ, Kroll S et al. Re-treatment with $^{131}$I tositwnomab in patients with non-Hodgkin's lymphoma who had previously responded to $^{131}$I tositwnomab. J Clin Oncol 2005;23:7985-93 https://doi.org/10.1200/JCO.2005.01.0892
  14. Shah J, Wang W, Harrough VD, Saville W, Meredith R, Shen S, et al. Retreatment with $^{90}$Y ibritwnomab tiuxetan in patients with B-cell non-Hodgkin's lymphoma. Leuk Lynphoma 2007;48:1736-44 https://doi.org/10.1080/10428190701528517
  15. Klaus B and Hubert MT. Accurate dosimetry: an essential step towards good clinical practice in nuclear medicine. Nucl Med Commun 2005;26:581-6 https://doi.org/10.1097/01.mnm.0000169204.13754.e2
  16. Ljungberg M, Sjo'' green K, Liu X, Frey E, Dewaraja Y, Strand SE. A 3-dimensional absorbed dose calculation method based on quantitative SPECT for radionuclide therapy: evaluation for $^{131}$I using Monte Carlo simulation. J Nucl Med 2002;43:1101-9
  17. Liu A, Wiliams LE, Wong JYC, Williams LE, Liu A, Wilczynski S et al. Monte Carlo assisted voxel source kernal method (MAVSK) for internal dosimetry. J Nucl Med Biol 1998;25:423-33 https://doi.org/10.1016/S0969-8051(98)00002-X
  18. Furhang EE, Chui CS, Sgouros G. A Monte Carlo approach to patient specific dosimetry. Med Phys 1996;23:1523 https://doi.org/10.1118/1.597882
  19. Yoriyaz H, Stabin MG, dos Santos A Monte Carlo MCNP-4B-hased absorbed dose distribution estimates for patient-specific dosimetry. J Nucl Med 2001;42:662
  20. DeNardo GL, Juweid ME, White CA, Wiseman GA, DeNardo SJ. Role of dosimetry in radioimmunotherapy planning and treatment dosing. Critical Rev Oncol Hematol 2001;39:203-18 https://doi.org/10.1016/S1040-8428(01)00109-3
  21. Matthay KK, Panina C, Huberty J, Price D, Glidden DV, Tang HR, et al. Correlation of tumor and whole-body dosimetry with tumor response and toxicity in refractory neuroblastoma treated with $^{131}$I MIBG. J Nucl Med 2001;42:1713-21
  22. DeNardo GL, Hartmann Siantar CL, DeNardo SJ. Radiation dosimetry for radionuclide therapy in a nonmyeloablative strategy. Cancer Biother Radiopharm 2002;17:107-18 https://doi.org/10.1089/10849780252824127
  23. Jerusalem G, Beguin Y, Fassotte MF, Najjar F, Paulus P, Rigo P, et al. Whole body emission tomography using $^{18}$F fluorodeoxyglucose for post treatment evaluation in Hodgkin's disease and non-Hodgkin's lymphoma has a higher diagnostic and prognostic value than classical computed tomography scan imaging. Blood 1999;94:429-33
  24. Moog F, Bangerter M, Diederichs CG, Guhlmann A, Kotzerke J, Merkle E, et al. Lymphoma: role of FDG-PET in nodal staging. Radiology 1997;203:795-800 https://doi.org/10.1148/radiology.203.3.9169707
  25. Stumpe KD, Urbinelli M, Steinert HC, Glanzmann C, Buck A, von Schulthess GK Whole-body positron emission tomography using fluorodeoxyglucose for staging of lymphoma: effectiveness and comparison with computed tomography. Bur J Nucl Med 1998;25:721-8 https://doi.org/10.1007/s002590050275
  26. Hong SP, Hahn JS, Lee JD, Bae SW, Youn MJ. $^{18}F-fluorodeoxyglucose-positron emission tomography in the staging of malignant lymphoma compared with CT and $^{67}$Ga scan. Yonsei Med J 2003;44:779-86 https://doi.org/10.3349/ymj.2003.44.5.779
  27. Carlo G, Kenneth R, Giuseppe LC. Current status of PET/CT for tumour volume definition in radiotherapy treatment planning for non-small cell lung cancer (NSCLC). Lung Cancer 2007;57:125-34 https://doi.org/10.1016/j.lungcan.2007.03.020
  28. Nestle U, Kremp S, Grosu AL. Practical integration of $^{18}$F-FDG-PET and PET-CT in the planning of radiotherapy for non-small cell lung cancer (NSCLC): the technical basis, ICRU-target volumes, problems, perspectives. Radiother Oncol 2006;81:209-25 https://doi.org/10.1016/j.radonc.2006.09.011
  29. Schoder H, Erdi YE, Chao K, Gonen M, Larson SM, Yeung HW. Clinical implications of different image reconstruction parameters for interpretation of whole-body PET studies in cancer patients. J Nucl Med 2004;45:559-66
  30. Paulino AC, Johnstone PA. FDG-PET in radiotherapy treatment planning: Pandora's box? Int J Radiat Oncol Biol Phys 2004;59:4-5 https://doi.org/10.1016/j.ijrobp.2003.10.045
  31. Bradley J, Thorstad WL, Mutic S, Miller TR, Dehdashti F, Siegel BA, et al. Impact of FDG-PET on radiation therapy volume delineation in non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2004;59:78-86 https://doi.org/10.1016/j.ijrobp.2003.10.044
  32. Giraud P, Grahek D, Montravers F, Carette MF, Deniaud-Alexandre E, Julia F, et al. CT and $^{18}$F-deoxyglucose (FDG) image fusion for optimization of conformal radiotherapy of lung cancers. Int J Radiat Oncol Biol Phys 2001;49:1249-57 https://doi.org/10.1016/S0360-3016(00)01579-0
  33. Erdi YE, Rosenzweig K, Erdi AK, Macapinlac HA, Hu YC, Braban LE, et al. Radiotherapy treatment planning for patients with non-small cell lung cancer using positron emission tomography (PET). Radiother Oncol 2002;62:51-60 https://doi.org/10.1016/S0167-8140(01)00470-4
  34. Koral KF, Dewaraja Y, Clarke LA, Li J, Zasadny KR, Rommelfanger SG, et al. Tumor-absorbed-dose estimates versus response in tositumomab therapy of previously untreated patients with follicular non-Hodgkin's lymphoma; preliminary report. Cancer Biother Radiopharm 2000;15:301-3 https://doi.org/10.1089/cbr.2000.15.301
  35. Dewaraja YK, Wilderman SJ, Ljungberg M, Koral KF, Zasadny K, Kaminiski MS. Accurate dosimetry in $^{131}$I radionuclide therapy using patient-specific, 3-dimensional methods for SPECT reconstruction and absorbed dese calculation. J Nucl Med 2005;46:840-9
  36. Joyce JM, Degirmenci B, Jacobs S, McCook B, Avril N. FDG PET CT assessment of treatment response after 90y ibritwnomab tiuxetan radioimmunotherapy. Clin Nucl Med 2005;30:564-8 https://doi.org/10.1097/01.rlu.0000170086.45627.99
  37. Torizuka T, Zasadny KR, Kison PV, Rommelfanger SG, Kaminski MS, Wahl RL. Metabolic response of non-Hodgkin's lymphoma to $^{131}$I-anti-B1 radioimmunotherapy: evaluation with FDG-PET. J Nucl Med 2000;41:999-1005
  38. Ulaner GA, Colletti PM, Conti PS. B-cell non-Hodgkin's lymphoma: PET/CT evaluation after $^{90}$Y-ibritwnomab tiuxetan radioimmunotherapy: initial experience. Radiology 2008;246:895-902 https://doi.org/10.1148/radiol.2463060588
  39. Koral K, Francis I, Kroll S, Zasadny KR, Kaminski MS, Wahl RL. Volume reduction versus radiation dose for tumors in previously untreated lymphoma patients who received $^{131}$Y tositwnomab therapy. Cancer 2002;94(Suppl 1):1258-63 https://doi.org/10.1002/cncr.10294
  40. Pauwels S, Barone R, Walrand S, Borson-Chazot F, Valkema R, Kvols LK, et al. Practical dosimetry of peptide receptor radionuclide therapy with $^{90}$Y-labeled somatostatin analogs. J Nucl Med 2005;46(Suppl 1):92S-8S