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核壳结构金纳米颗粒作为镝/钬体内发生器的载体。

Core-shell structured gold nanoparticles as carrier for Dy/Ho in vivo generator.

作者信息

Wang Runze, Ponsard Bernard, Wolterbeek Hubert, Denkova Antonia

机构信息

Applied Radiation and Isotopes, Department of Radiation Science and Technology, Faculty of Applied Sciences, Delft University of Technology, Mekelweg 15, 2629 JB, Delft, The Netherlands.

Belgian Nuclear Research Centre, SCK CEN, Boeretang 200, 2400, Mol, Belgium.

出版信息

EJNMMI Radiopharm Chem. 2022 Jul 19;7(1):16. doi: 10.1186/s41181-022-00170-3.

Abstract

BACKGROUND

Radionuclide therapy (RNT) has become a very important treatment modality for cancer nowadays. Comparing with other cancer treatment options, sufficient efficacy could be achieved in RNT with lower toxicity. β emitters are frequently used in RNT due to the long tissue penetration depth of the β particles. The dysprosium-166/holmium-166 (Dy/Ho) in vivo generator shows great potential for treating large malignancies due to the long half-life time of the mother nuclide Dy and the emission of high energy β from the daughter nuclide Ho. However, the internal conversion occurring after β decay from Dy to Ho could cause the release of about 72% of Ho when Dy is bound to conventional chelators. The aim of this study is to develop a nanoparticle based carrier for Dy/Ho in vivo generator such that the loss of the daughter nuclide Ho induced by internal conversion is prevented. To achieve this goal, we radiolabelled platinum-gold bimetallic nanoparticles (PtAuNPs) and core-shell structured gold nanoparticles (AuNPs) with Dy and studied the retention of both Dy and Ho under various conditions.

RESULTS

The Dy was co-reduced with gold and platinum precursor to form the DyAu@AuNPs and DyPtAuNPs. The Dy radiolabelling efficiency was determined to be 60% and 70% for the two types of nanoparticles respectively. The retention of Dy and Ho were tested in MiliQ water or 2.5 mM DTPA for a period of 72 h. In both cases, more than 90% of both Dy and Ho was retained. The results show that the incorporation of Dy in AuNPs can prevent the escape of Ho released due to internal conversion.

CONCLUSION

We developed a chelator-free radiolabelling method for Dy with good radiolabelling efficiency and very high stability and retention of the daughter nuclide Ho. The results from this study indicate that to avoid the loss of the daughter radionuclides by internal conversion, carriers composed of electron-rich materials should be used.

摘要

背景

放射性核素治疗(RNT)如今已成为癌症治疗的一种非常重要的方式。与其他癌症治疗选择相比,RNT能以较低毒性实现足够的疗效。由于β粒子在组织中的穿透深度较长,β发射体常用于RNT。镝 - 166/钬 - 166(Dy/Ho)体内发生器因其母体核素Dy的半衰期长以及子体核素Ho发射高能β,在治疗大型恶性肿瘤方面显示出巨大潜力。然而,当Dy与传统螯合剂结合时,Dy向Ho的β衰变后发生的内转换会导致约72%的Ho释放。本研究的目的是开发一种用于Dy/Ho体内发生器的基于纳米颗粒的载体,以防止因内转换导致子体核素Ho的损失。为实现这一目标,我们用Dy对铂 - 金双金属纳米颗粒(PtAuNPs)和核壳结构金纳米颗粒(AuNPs)进行放射性标记,并研究了在各种条件下Dy和Ho的保留情况。

结果

Dy与金和铂前驱体共同还原形成DyAu@AuNPs和DyPtAuNPs。两种纳米颗粒的Dy放射性标记效率分别确定为60%和70%。在超纯水或2.5 mM二乙三胺五乙酸(DTPA)中对Dy和Ho的保留情况进行了72小时的测试。在这两种情况下,Dy和Ho的保留率均超过90%。结果表明,Dy掺入AuNPs中可防止因内转换而释放的Ho逸出。

结论

我们开发了一种用于Dy的无螯合剂放射性标记方法,具有良好的放射性标记效率以及子体核素Ho的非常高的稳定性和保留率。本研究结果表明,为避免因内转换导致子体放射性核素的损失,应使用由富电子材料组成的载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c30/9296738/67316608fe1c/41181_2022_170_Fig1_HTML.jpg

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