p-Isothiocyanatobenzyl-desferrioxamine: a new bifunctional chelate for facile radiolabeling of monoclonal antibodies with zirconium-89 for immuno-PET imaging.
p-Isothiocyanatobenzyl-desferrioxamine: a new bifunctional chelate for facile radiolabeling of monoclonal antibodies with zirconium-89 for immuno-PET imaging.
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DOI：
10.1007/s00259-009-1263-1
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发表时间：
2010-02
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.;Vosjan, Maria J. W. D.;Visser, Gerard W. M.;Budde, Marianne;Jurek, Paul;Kiefer, Garry E.;van Dongen, Guus A. M. S.
关键词：
免疫PET是一种新兴的成像工具，用于选择用于成像和治疗的高潜力抗体（mAb）。正电子发射体锆-89（89 Zr）对于具有完整mAb的免疫PET具有吸引人的特性。之前，我们已经描述了通过双功能螯合物（BFC）四氟苯酚-N-琥珀酰去铁醛（TFP-N-sucDf）将89 Zr稳定偶联至mAb的多步程序。为了使89 Zr-免疫-PET能够广泛使用，我们现在引入新型BFC对异硫氰基苄基-去铁胺B（Df-Bz-NCS），并将其在89 Zr-免疫-PET中的性能与参比BFC TFP-N-sucDf进行比较。用Df-Bz-NCS预修饰三种mAb，并在不同pH下用89 Zr标记，以评估放射性标记的反应动力学和耐用性。在不同的缓冲液和人血清中评价89 Zr-Df-Bz-NCS-和89 Zr-N-sucDf-缀合物的稳定性。在荷瘤小鼠中进行了比较生物分布和PET研究。选择的缀合条件导致螯合物：mAb取代比为约1.5：1。在最佳放射性标记条件（pH 6.8-7.2）下，在室温下孵育60分钟后，放射化学产率>85%，产生具有保留的完整性和免疫反应性的放射免疫缀合物。新的放射性免疫缀合物在37°C下在血清中非常稳定长达7天，具有<5%的89 Zr释放，并且当在4°C下储存在适当的缓冲液中时，与参考缀合物相比同样稳定。在生物分布和成像实验中，新的和参考的放射性免疫缀合物在裸鼠肿瘤中显示出高的和相似的蓄积。新型Df-Bz-NCS BFC允许高效且容易地制备最佳性能的89 Zr标记的mAb，促进89 Zr-免疫-PET作为成像工具的进一步探索。
Immuno-PET is an emerging imaging tool for the selection of high potential antibodies (mAbs) for imaging and therapy. The positron emitter zirconium-89 (89Zr) has attractive characteristics for immuno-PET with intact mAbs. Previously, we have described a multi-step procedure for stable coupling of 89Zr to mAbs via the bifunctional chelate (BFC) tetrafluorophenol-N-succinyldesferal (TFP-N-sucDf). To enable widespread use of 89Zr-immuno-PET, we now introduce the novel BFC p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) and compare its performance in 89Zr-immuno-PET with the reference BFC TFP-N-sucDf. Three mAbs were premodified with Df-Bz-NCS and labeled with 89Zr at different pHs to assess the reaction kinetics and robustness of the radiolabeling. Stability of both 89Zr-Df-Bz-NCS- and 89Zr-N-sucDf-conjugates was evaluated in different buffers and human serum. Comparative biodistribution and PET studies in tumor-bearing mice were undertaken. The selected conjugation conditions resulted in a chelate:mAb substitution ratio of about 1.5:1. Under optimal radiolabeling conditions (pH between 6.8–7.2), the radiochemical yield was >85% after 60 min incubation at room temperature, resulting in radioimmunoconjugates with preserved integrity and immunoreactivity. The new radioimmunoconjugate was very stable in serum for up to 7 days at 37°C, with <5% 89Zr release, and was equally stable compared to the reference conjugate when stored in the appropriate buffer at 4°C. In biodistribution and imaging experiments, the novel and the reference radioimmunoconjugates showed high and similar accumulation in tumors in nude mice. The novel Df-Bz-NCS BFC allows efficient and easy preparation of optimally performing 89Zr-labeled mAbs, facilitating further exploration of 89Zr-immuno-PET as an imaging tool.
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影响因子：
3.5
作者：
de Jong, Hugo W. A. M.;van Velden, Floris H. P.;Lammertsma, Adriaan A.
通讯作者：
Lammertsma, Adriaan A.
DOI：
10.1007/s00259-006-0160-0
发表时间：
2006-11-01
影响因子：
9.1
作者：
Perk, Lars R.;Visser, Otto J.;van Dongen, Guus A. M. S.
通讯作者：
van Dongen, Guus A. M. S.
影响因子：
9.3
作者：
Wu, Anna M.
通讯作者：
Wu, Anna M.
DOI：
10.1007/s00259-008-0774-5
发表时间：
2008-10-01
影响因子：
9.1
作者：
Perk, Lars R.;Walsum, Marijke Stigter-van;van Dongen, Guus A. M. S.
通讯作者：
van Dongen, Guus A. M. S.
影响因子：
2.9
作者：
MEARES, CF;MCCALL, MJ;MCTIGUE, M
通讯作者：
MCTIGUE, M