Preparation and evaluation of 89Zr-Zevalin for monitoring of 90Y-Zevalin biodistribution with positron emission tomography
Preparation and evaluation of 89Zr-Zevalin for monitoring of 90Y-Zevalin biodistribution with positron emission tomography
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DOI：
10.1007/s00259-006-0160-0
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发表时间：
2006-11-01
影响因子：
9.1
通讯作者：
van Dongen, Guus A. M. S.
中科院分区：
文献类型：
--
作者：
Perk, Lars R.;Visser, Otto J.;van Dongen, Guus A. M. S.
目的：评价Zr-89是否可以作为PET替代标记用于清髓放射免疫治疗前定量y -90-伊布单抗替克坦（y -90-泽伐林）的生物分布和剂量测定。方法：通过引入n -琥珀酰地夫醛（N-sucDf）作为第二螯合物，用Zr-89标记泽伐林。为了比较Zr-89-Zevalin和Y-88-Zevalin（作为Y-90的替代品）的体外稳定性，将样品在37℃的人血清中孵育6天。在携带非霍奇金淋巴瘤（NHL）异种移植系Ramos的裸鼠体内共注射Zr-89-Zevalin和Y-88-Zevalin，分别在p.i. 24、48、72和144小时进行生物分布评估。Zr-89-Zevalin- PET的临床表现是通过对一名2周前接受了[F-18] FDG- PET治疗的NHL患者的初步影像学研究来评估的。结果：用N-sucDf修饰泽伐林后，N-sucDf与抗体的摩尔比为0.83 +/- 0.04。经放射性标记和纯化后，Zr-89-Zevalin的放射化学纯度和免疫反应性均超过95%和80%。zr -89-泽瓦林在血清中表现出与y -88-泽瓦林相同的稳定性，在6天内的放射化学纯度为95%。共注射Zr-89- zevalin和Y-88- zevalin偶联物的生物分布非常相似，除了Zr-89在72和144 h p.i时的肝脏和骨骼蓄积显著高于Y-88。注射Zr-89-Zevalin后获得的PET图像显示，所有已知的肿瘤病灶都有明确的靶向性。结论：Zr-89-Zevalin和Y-88-Zevalin在小鼠体内的生物分布非常相似，表明Zr-89-Zevalin pet可能很适合用于预测Y-90-Zevalin在清骨髓环境中的生物分布。
Purpose: To evaluate whether Zr-89 can be used as a PET surrogate label for quantification of Y-90-ibritumomab tiuxetan (Y-90-Zevalin) biodistribution and dosimetry before myeloablative radioimmunotherapy.Methods: Zevalin was labelled with Zr-89 by introducing N-succinyldesferal (N-sucDf) as a second chelate. For comparison of the in vitro stability of Zr-89-Zevalin and Y-88-Zevalin ( as a substitute for Y-90), samples were incubated in human serum at 37 degrees C up to 6 days. Biodistribution of Zr-89-Zevalin and Y-88-Zevalin was assessed at 24, 48, 72 and 144 h p.i. by co-injection in nude mice bearing the non-Hodgkin's lymphoma (NHL) xenograft line Ramos. The clinical performance of Zr-89-Zevalin- PET was evaluated via a pilot imaging study in a patient with NHL, who had undergone [F-18] FDG- PET 2 weeks previously.Results: Modification of Zevalin with N-sucDf resulted in an N-sucDf-to-antibody molar ratio of 0.83 +/- 0.04. After radiolabelling and purification, the radiochemical purity and immunoreactivity of Zr-89-Zevalin always exceeded 95% and 80%, respectively. Zr-89-Zevalin showed the same stability in serum as Y-88-Zevalin, with a radiochemical purity > 95% during a period of 6 days. The co-injected Zr-89-Zevalin and Y-88-Zevalin conjugates showed a very similar biodistribution, except for liver and bone accumulation at 72 and 144 h p.i., which was significantly higher for Zr-89 than for Y-88. PET images obtained after injection of Zr-89-Zevalin showed clear targeting of all known tumour lesions.Conclusion: Zr-89-Zevalin and Y-88-Zevalin showed a very similar biodistribution in mice, implying that Zr-89-Zevalin-PET might be well suited for prediction of Y-90-Zevalin biodistribution in a myeloablative setting.