High-dose radioimmunotherapy with 90Y-ibritumomab tiuxetan:: Comparative dosimetric study for tailored treatment
High-dose radioimmunotherapy with 90Y-ibritumomab tiuxetan:: Comparative dosimetric study for tailored treatment
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DOI：
10.2967/jnumed.107.044016
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发表时间：
2007-11-01
影响因子：
9.3
通讯作者：
Ferrucci, Pier Francesco
中科院分区：
文献类型：
--
作者：
Cremonesi, Marta;Ferrari, Mahila;Ferrucci, Pier Francesco
剂量测定后，应用高剂量y -90易博单抗替克坦治疗和相关的自体干细胞移植（ASCT）。本文报道了3种不同方法的剂量学结果，包括图像校正和实际器官质量校正。我们的第一个目标是确定y -90依布单抗替克坦高剂量治疗中采用的最可靠和可行的剂量学方法。第二个目标是验证规定活性的安全性和干细胞回输的最佳时机。方法：22例难治性非霍奇金淋巴瘤患者分为3个活动组，活动量均为55.5 MBq/kg。对器官（除红骨髓外）的任意切断20 Gy被定义为患者招募的安全限度。当再输注干细胞的剂量小于50mgy时，ASCT被认为是低风险的。给予In-111-ibritumomab tixetan （185 MBq）进行剂量测定。注射后130小时采集血液样本，得出个体血液清除率和红骨髓剂量。注射后7 d获得5张全身图像。同时进行了透射扫描和低剂量CT扫描。使用共轭视图技术，并对图像进行背景，散射和衰减校正。使用OLINDA/EXM软件计算吸收剂量，根据个体器官质量调整剂量。采用3种方法对生物分布数据进行了共轭观剂量学分析。方法A是一种患者特异性方法，应用背景、散射和衰减校正，使用OLINDA/EXM软件计算吸收剂量，并根据个体器官质量和单独估计的血容量调整剂量。方法B是一种参考方法，使用参考男女幽灵的器官肿块。方法C是使用标准血和红骨髓体积的简化方法，不进行校正。结果：A法剂量估计（mGy/MBq）的中位数和范围（括号内）分别为肺1.7（0.3 ~ 3.5）、肝2.8（1.8 ~ 10.6）、肾1.7（0.6 ~ 3.8）、脾1.9（0.8 ~ 5.0）、红骨髓0.8（0.4 ~ 1.0）、睾丸2.8（1.3 ~ 4.7）。没有患者需要推迟ASCT。由于标准肿块和实际肿块之间的差异，B方法的吸收剂量与A方法的差异可达100%，肾的80%，脾的335%，血的80%。与A方法相比，C方法导致肺剂量高估4倍，肝剂量高估2倍，肾剂量高估5倍，脾剂量高估7倍，红骨髓剂量高估2倍，睾丸剂量高估2倍。结论：在高剂量y -90依布单抗替克坦治疗中，推荐采用患者特异性剂量法结合图像校正和质量调整，肝脏是剂量限制器官。过于简化的剂量测定法可能会对关键器官的剂量、给药活性的推荐值和ASCT的时间提供不准确的信息。
High-dose Y-90-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 Y-90-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. In-111-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 Y-90-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.