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放射性标记单克隆抗体 BC8 的生物动力学:血液系统恶性肿瘤的体内分布和剂量学差异。

Biokinetics of Radiolabeled Monoclonal Antibody BC8: Differences in Biodistribution and Dosimetry Among Hematologic Malignancies.

机构信息

Department of Radiology, University of Washington, Seattle, Washington

Department of Radiology, University of Washington, Seattle, Washington.

出版信息

J Nucl Med. 2020 Sep;61(9):1300-1306. doi: 10.2967/jnumed.119.234443. Epub 2020 Mar 13.

DOI:10.2967/jnumed.119.234443
PMID:32169919
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7456175/
Abstract

We reviewed In-DOTA-anti-CD45 antibody (BC8) imaging and bone marrow biopsy measurements to ascertain the biodistribution and biokinetics of the radiolabeled antibody and to investigate differences based on type of hematologic malignancy. Serial whole-body scintigraphic images (4 time points) were obtained after infusion of the In-DOTA-BC8 (176-406 MBq) into 52 adult patients with hematologic malignancies (lymphoma, multiple myeloma, acute myeloid leukemia, and myelodysplastic syndrome). Counts were obtained for the regions of interest for spleen, liver, kidneys, testicles (in men), and 2 marrow sites (acetabulum and sacrum), and correction for attenuation and background was made. Bone marrow biopsies were obtained 14-24 h after infusion, and the percentage of administered activity was determined. Absorbed radiation doses were calculated. Initial uptake in liver averaged 32% ± 8.4% (SD) of administered activity (52 patients), which cleared monoexponentially with a biologic half-time of 293 ± 157 h (33 patients) or did not clear (19 patients). Initial uptake in spleen averaged 22% ± 12% and cleared with a biologic half-time of 271 ± 185 h (36 patients) or longer (6 patients). Initial uptake in kidney averaged 2.4% ± 2.0% and cleared with a biologic half-time of 243 ± 144 h (27 patients) or longer (9 patients). Initial uptake in red marrow averaged 23% ± 11% and cleared with a biologic half-time of 215 ± 107 h (43 patients) or longer (5 patients). Whole-body retention half-time averaged 198 ± 75 h. Splenic uptake was higher in the AML/MDS group than in the lymphoma group ( ≤ 0.05) or the multiple myeloma group ( ≤ 0.10). Liver represented the dose-limiting organ. For liver uptake, no significant differences were observed among the 3 malignancy groups. Average calculated radiation absorbed doses per unit of administered activity for a therapy infusion of Y-DOTA-BC8 were 0.35 ± 0.20 cGy/MBq for red marrow, 0.80 ± 0.24 cGy/MBq for liver, 3.0 ± 1.4 cGy/MBq for spleen, 0.055 ± 0.014 cGy/MBq for total body, 0.21 ± 0.15 cGy/MBq for osteogenic cells, and 0.17 ± 0.15 cGy/MBq for kidneys. In-DOTA-BC8 had a long retention time in liver, spleen, kidneys, and red marrow, and the highest absorbed doses were in spleen and liver. Few differences were observed by malignancy type. The exception was greater splenic uptake in the leukemia/MDS group than in the lymphoma or multiple myeloma group.

摘要

我们回顾了 In-DOTA-anti-CD45 抗体(BC8)的成像和骨髓活检测量结果,以确定放射性标记抗体的生物分布和生物动力学,并根据血液恶性肿瘤的类型研究差异。在 52 名患有血液恶性肿瘤(淋巴瘤、多发性骨髓瘤、急性髓性白血病和骨髓增生异常综合征)的成年患者中,在输注 In-DOTA-BC8(176-406MBq)后获得了 4 次全身闪烁扫描图像(4 个时间点)。对感兴趣的区域(脾脏、肝脏、肾脏、睾丸(男性)和 2 个骨髓部位(髋臼和骶骨)进行了计数,并进行了衰减和背景校正。在输注后 14-24 小时获得骨髓活检,并确定给药活性的百分比。计算吸收的辐射剂量。肝脏的初始摄取平均为 32%±8.4%(SD)(52 例患者),以 293±157h(33 例患者)或未清除的单指数清除(19 例患者)。脾脏的初始摄取平均为 22%±12%,并以 271±185h(36 例患者)或更长时间的生物半衰期清除(6 例患者)。肾脏的初始摄取平均为 2.4%±2.0%,并以 243±144h(27 例患者)或更长时间的生物半衰期清除(9 例患者)。红骨髓的初始摄取平均为 23%±11%,并以 215±107h(43 例患者)或更长时间的生物半衰期清除(5 例患者)。全身保留半衰期平均为 198±75h。AML/MDS 组的脾脏摄取量高于淋巴瘤组(≤0.05)或多发性骨髓瘤组(≤0.10)。肝脏是剂量限制器官。对于肝脏摄取,3 种恶性肿瘤组之间无显著差异。Y-DOTA-BC8 治疗输注的每单位给药活性的平均计算吸收剂量为 0.35±0.20cGy/MBq 用于红骨髓,0.80±0.24cGy/MBq 用于肝脏,3.0±1.4cGy/MBq 用于脾脏,0.055±0.014cGy/MBq 用于全身,0.21±0.15cGy/MBq 用于成骨细胞,0.17±0.15cGy/MBq 用于肾脏。In-DOTA-BC8 在肝脏、脾脏、肾脏和红骨髓中的滞留时间较长,吸收剂量最高的部位是脾脏和肝脏。根据恶性肿瘤的类型观察到很少的差异。例外的是,白血病/骨髓增生异常综合征组的脾脏摄取量高于淋巴瘤或多发性骨髓瘤组。