Perk Lars R, Visser Otto J, Stigter-van Walsum M, Vosjan Maria J W D, Visser Gerard W M, Zijlstra Josée M, Huijgens Peter C, van Dongen Guus A M S
Department of Otolaryngology/Head and Neck Surgery, VU University Medical Centre, De Boelelaan 1117, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
Eur J Nucl Med Mol Imaging. 2006 Nov;33(11):1337-45. doi: 10.1007/s00259-006-0160-0. Epub 2006 Jul 11.
To evaluate whether (89)Zr can be used as a PET surrogate label for quantification of (90)Y-ibritumomab tiuxetan ((90)Y-Zevalin) biodistribution and dosimetry before myeloablative radioimmunotherapy.
Zevalin was labelled with (89)Zr by introducing N-succinyldesferal (N-sucDf) as a second chelate. For comparison of the in vitro stability of (89)Zr-Zevalin and (88)Y-Zevalin (as a substitute for (90)Y), samples were incubated in human serum at 37 degrees C up to 6 days. Biodistribution of (89)Zr-Zevalin and (88)Y-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 (89)Zr-Zevalin-PET was evaluated via a pilot imaging study in a patient with NHL, who had undergone [(18)F]FDG-PET 2 weeks previously.
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 (89)Zr-Zevalin always exceeded 95% and 80%, respectively. (89)Zr-Zevalin showed the same stability in serum as (88)Y-Zevalin, with a radiochemical purity >95% during a period of 6 days. The co-injected (89)Zr-Zevalin and (88)Y-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 (89)Zr than for (88)Y. PET images obtained after injection of (89)Zr-Zevalin showed clear targeting of all known tumour lesions.
(89)Zr-Zevalin and (88)Y-Zevalin showed a very similar biodistribution in mice, implying that (89)Zr-Zevalin-PET might be well suited for prediction of (90)Y-Zevalin biodistribution in a myeloablative setting.
评估⁸⁹Zr是否可用作正电子发射断层扫描（PET）替代标记物，以在清髓性放射免疫治疗前对⁹⁰Y-替伊莫单抗（⁹⁰Y-Zevalin）的生物分布和剂量测定进行定量分析。
通过引入N-琥珀酰去铁胺（N-sucDf）作为第二种螯合剂，用⁸⁹Zr标记Zevalin。为比较⁸⁹Zr-Zevalin和⁸⁸Y-Zevalin（作为⁹⁰Y的替代物）的体外稳定性，将样品在37℃的人血清中孵育长达6天。通过在携带非霍奇金淋巴瘤（NHL）异种移植瘤系Ramos的裸鼠中共同注射，在注射后24、48、72和144小时评估⁸⁹Zr-Zevalin和⁸⁸Y-Zevalin的生物分布。通过对一名两周前接受过[¹⁸F]FDG-PET检查的NHL患者进行的初步成像研究，评估⁸⁹Zr-Zevalin-PET的临床性能。
用N-sucDf修饰Zevalin后，N-sucDf与抗体的摩尔比为0.83±0.04。放射性标记和纯化后，⁸⁹Zr-Zevalin的放射化学纯度和免疫反应性始终分别超过95%和80%。⁸⁹Zr-Zevalin在血清中的稳定性与⁸⁸Y-Zevalin相同，在6天内放射化学纯度>95%。共同注射的⁸⁹Zr-Zevalin和⁸⁸Y-Zevalin偶联物显示出非常相似的生物分布，但在注射后72和144小时肝脏和骨骼的蓄积除外，⁸⁹Zr的蓄积明显高于⁸⁸Y。注射⁸⁹Zr-Zevalin后获得的PET图像显示所有已知肿瘤病变均有清晰的靶向性。
⁸⁹Zr-Zevalin和⁸⁸Y-Zevalin在小鼠中显示出非常相似的生物分布，这意味着⁸⁹Zr-Zevalin-PET可能非常适合预测清髓性治疗环境中⁹⁰Y-Zevalin的生物分布。
