α粒子发射体标记抗体：213Bi-HuM195（抗CD33）在白血病患者中的药代动力学和剂量学研究

Pharmacokinetics and dosimetry of an alpha-particle emitter labeled antibody: 213Bi-HuM195 (anti-CD33) in patients with leukemia.

作者信息

Sgouros G, Ballangrud A M, Jurcic J G, McDevitt M R, Humm J L, Erdi Y E, Mehta B M, Finn R D, Larson S M, Scheinberg D A

机构信息

Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

出版信息

J Nucl Med. 1999 Nov;40(11):1935-46.

PMID:10565792

Abstract

UNLABELLED

Data from nine patients with leukemia participating in a phase I activity-escalation study of HuM195, labeled with the alpha-particle emitter 213Bi (half-life = 45.6 min), were used to estimate pharmacokinetics and dosimetry. This is the first trial using an alpha-particle emitter in humans. The linear energy transfer of alpha particles is several hundredfold greater than that of beta emissions. The range in tissue is approximately 60-90 microm.

METHODS

The activity administered to patients ranged from 0.6 to 1.6 GBq. Patient imaging was initiated at the start of each injection. Thirty 1-min images followed by ten 3-min images were collected in dynamic mode; a 20% photopeak window centered at 440 keV was used. Blood samples were collected until 3 h postinjection and counted in a gamma counter. Contours around the liver and spleen were drawn on the anterior and posterior views and around a portion of the spine on the posterior views. No other organs were visualized.

RESULTS

The percentage injected dose in the liver and spleen volumes increased rapidly over the first 10-15 min to a constant value for the remaining hour of imaging, yielding a very rapid uptake followed by a plateau in the antibody uptake curves. The kinetic curves were integrated to yield cumulated activity. The mean energy emitted per nuclear transition for 213Bi and its daughters, adjusted by a relative biologic effectiveness of 5 for alpha emissions, was multiplied by the cumulated activity to yield the absorbed dose equivalent. Photon dose to the total body was determined by calculating a photon-absorbed fraction. The absorbed dose equivalent to liver and spleen volumes ranged from 2.4 to 11.2 and 2.9 to 21.9 Sv, respectively. Marrow (or leukemia) mean dose ranged from 6.6 to 12.2 Sv. The total-body dose (photons only) ranged from 2.2 x 10(-4) to 5.8 x 10(-4) Gy.

CONCLUSION

This study shows that patient imaging of 213Bi, an alpha-particle emitter, labeled to HuM195 is possible and may be used to derive pharmacokinetics and dosimetry. The absorbed dose ratio between marrow, liver and spleen volumes and the whole body for 213Bi-HuM195 is 1000-fold greater than that commonly observed with beta-emitting radionuclides used for radioimmunotherapy.

摘要

未标记

来自9名参与HuM195的I期剂量递增研究的白血病患者的数据被用于估算药代动力学和剂量测定，HuM195用α粒子发射体213Bi（半衰期 = 45.6分钟）标记。这是首次在人体中使用α粒子发射体的试验。α粒子的传能线密度比β发射大数百倍。在组织中的射程约为60 - 90微米。

方法

给予患者的活度范围为0.6至1.6 GBq。每次注射开始时启动患者成像。以动态模式收集30张1分钟图像，随后收集10张3分钟图像；使用以440 keV为中心的20%光电峰窗。在注射后3小时内采集血样并在γ计数器中计数。在前后位视图上绘制肝脏和脾脏周围的轮廓，在后位视图上绘制脊柱一部分周围的轮廓。未观察到其他器官。

结果

肝脏和脾脏体积中的注射剂量百分比在最初10 - 15分钟内迅速增加，在成像的剩余1小时内达到恒定值，在抗体摄取曲线中产生非常快速的摄取，随后达到平台期。对动力学曲线进行积分以得出累积活度。213Bi及其子体每次核跃迁发射的平均能量，通过α发射的相对生物效应5进行调整，乘以累积活度以得出吸收剂量当量。通过计算光子吸收分数确定全身的光子剂量。肝脏和脾脏体积的吸收剂量当量分别为2.4至11.2 Sv和2.9至21.9 Sv。骨髓（或白血病）平均剂量为6.6至12.2 Sv。全身剂量（仅光子）为2.2×10−4至5.8×10−4 Gy。