Department of Radiation Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
J Nucl Med. 2010 Jan;51(1):150-7. doi: 10.2967/jnumed.109.066597. Epub 2009 Dec 15.
To determine whether the therapeutic effect of (90)Y-ibritumomab might be enhanced by a full course of rituximab followed by single dose of (90)Y-ibritumomab, the trial included pre- and post-rituximab treatment imaging with (111)In-ibritumomab and blood pharmacokinetics. Comparison of the pre- and post-rituximab imaging and blood data allowed for the assessment of impact of rituximab on (90)Y-ibritumomab dosimetry.
Seventeen patients with relapsed B cell non-Hodgkin lymphoma first received 250 mg/m(2) of rituximab plus 185 MBq of (111)In-ibritumomab for initial dosimetry evaluation. In weeks 2-4, patients received 3 weekly 375 mg/m(2) doses of rituximab. In week 6, patients received a 250 mg/m(2) dose of rituximab plus 185 MBq of (111)In-ibritumomab for a second dosimetry evaluation. Five sequential, whole-body gamma-camera images were acquired after the (111)In-ibritumomab injection. Calculated radiation doses were based on patient-specific organ masses. For each patient, paired comparison of radiation doses before and after rituximab treatment was performed. Paired comparison of residence times for spleen and tumor was also performed.
Before rituximab treatment, the median radiation dose (mGy/MBq) was 0.48 (range, 0.24-0.86) for total body, 3.7 (range, 2.1-11.6) for liver, 6.1 (range, 1.8-17.8) for spleen, 3.3 (range, 2.0-4.7) for kidneys, 2.4 (range, 1.3-3.7) for heart wall, 1.1 (range, 0.4-2.3) for lungs, 0.79 (range, 0.32-1.22) for marrow from blood, and 18.1 (range, 4.7-98.9) for tumor. Paired comparisons were performed in 16 patients only because human antimurine antibody developed in 1 patient. The median change was 0.007 mGy/MBq for body, -0.14 mGy/MBq for liver, -0.31 mGy/MBq for kidneys, 0.38 mGy/MBq for heart wall, -0.17 mGy/MBq for lungs, and 0.046 mGy/MBq for marrow from blood. The median change in residence time was -0.92 h for spleen and -0.24 h for tumor. The changes were statistically insignificant for total body, liver, kidneys, lungs, and marrow from blood. The median residence times, or mGy/MBq if there were no volume changes, decreased 24% for spleen (P = 0.0005) and 28% for tumor (P = 0.005). The median radiation dose to heart wall increased 16%, which was statistically significant (P = 0.002).
Changes in (90)Y-ibritumomab dosimetry after 4 wk of rituximab treatment were not significant for most organs, except for the heart wall. The reduction of spleen and tumor residence times is more likely to be due to the therapeutic effects of rituximab.
确定是否可以通过全程利妥昔单抗治疗加单次（90）Y-依鲁替尼来增强（90）Y-依鲁替尼的治疗效果，本试验包括在利妥昔单抗治疗前后进行（111）In-依鲁替尼治疗前和治疗后成像以及血液药代动力学检查。比较治疗前后的成像和血液数据可以评估利妥昔单抗对（90）Y-依鲁替尼剂量学的影响。
17 例复发性 B 细胞非霍奇金淋巴瘤患者首先接受 250mg/m2 的利妥昔单抗加 185MBq 的（111）In-依鲁替尼进行初始剂量学评估。在第 2-4 周，患者接受每周 3 次 375mg/m2 的利妥昔单抗治疗。在第 6 周，患者接受 250mg/m2 的利妥昔单抗加 185MBq 的（111）In-依鲁替尼进行第二次剂量学评估。在（111）In-依鲁替尼注射后进行 5 次连续的全身伽玛相机成像。计算出的辐射剂量基于患者的特定器官质量。对每个患者进行利妥昔单抗治疗前后的辐射剂量进行配对比较。还对脾脏和肿瘤的停留时间进行了配对比较。
在利妥昔单抗治疗前，中位数辐射剂量（mGy/MBq）分别为全身 0.48（范围，0.24-0.86）、肝脏 3.7（范围，2.1-11.6）、脾脏 6.1（范围，1.8-17.8）、肾脏 3.3（范围，2.0-4.7）、心脏壁 2.4（范围，1.3-3.7）、肺 1.1（范围，0.4-2.3）、骨髓 0.79（范围，0.32-1.22）和肿瘤 18.1（范围，4.7-98.9）。由于 1 例患者产生了人抗鼠抗体，仅对 16 例患者进行了配对比较。中位数变化为 0.007mGy/MBq 全身、-0.14mGy/MBq 肝脏、-0.31mGy/MBq 肾脏、0.38mGy/MBq 心脏壁、-0.17mGy/MBq 肺和 0.046mGy/MBq 骨髓。脾脏和肿瘤停留时间的中位数变化分别为-0.92h 和-0.24h。全身、肝脏、肾脏、肺和骨髓的变化无统计学意义。脾脏停留时间中位数下降 24%（P=0.0005），肿瘤停留时间中位数下降 28%（P=0.005）。心脏壁的辐射剂量中位数增加 16%，具有统计学意义（P=0.002）。
利妥昔单抗治疗 4 周后，（90）Y-依鲁替尼的剂量学变化在大多数器官中并不显著，除了心脏壁。脾脏和肿瘤停留时间的减少更可能是由于利妥昔单抗的治疗效果。
