用于靶向α治疗的磷酸镧纳米颗粒作为（223）Ra和（225）Ra载体的合成与表征

Synthesis and characterization of lanthanum phosphate nanoparticles as carriers for (223)Ra and (225)Ra for targeted alpha therapy.

作者信息

Rojas J V, Woodward J D, Chen N, Rondinone A J, Castano C H, Mirzadeh S

机构信息

Department of Mining and Nuclear Engineering, Missouri University for Science and Technology, Rolla, MO 65401; Center for Nanophase Materials Sciences and Nuclear Safety and Isotope Technology Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831.

Center for Nanophase Materials Sciences and Nuclear Safety and Isotope Technology Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831.

出版信息

Nucl Med Biol. 2015 Jul;42(7):614-20. doi: 10.1016/j.nucmedbio.2015.03.007. Epub 2015 Apr 1.

DOI:10.1016/j.nucmedbio.2015.03.007

PMID:25900730

Abstract

INTRODUCTION

Targeted alpha therapy (TAT) has the potential for killing micro-metastases with minimum collateral damage to surrounding healthy tissue. In-vivo generator radionuclides, such as(223)Ra, (225)Ra, and (225)Ac, are of special interest for radiotherapeutic applications as they emit multiple α-particles during their decay. Utilizing appropriate carriers capable of retaining both the parent radioisotope as well as daughter products is important for the effective delivery of the radioisotope to the tumor site while mitigating global in vivo radiotoxicity. In this work, LaPO4 core and core+2 shells nanoparticles (NPs) (NPs with 2 layers of cold LaPO4 deposited on the core surfaces) were synthesized containing either (223)Ra or(225)Ra/(225)Ac, and the retention of the parents and daughters within the NPs in vitro was investigated.

METHODS

Core LaPO4 NPs were synthesized in aqueous solution by reacting 1 equivalent of La(NO3)3, along with few microcuries of either (223)Ra or (225)Ra/(225)Ac, with 1 equivalent of sodium tripolyphosphate (TPP) under moderate heating and purified by membrane dialysis. Core-shell NPs were also synthesized with one (core+1 shell) and two (core+2 shells) cold LaPO4 layers deposited onto the radioactive cores. The NPs were then characterized by transmission electron microscopy (TEM) and powder x-ray diffraction (XRD). Identification and quantification of radioactive parents and daughters released from the NPs in vitro were investigated using gamma-ray spectroscopy.

RESULTS

XRD and TEM analysis revealed that the NPs crystallized in the rhabdophane phase with mean diameters of 3.4 and 6.3nm for core and core+2 shells, respectively. The core LaPO4 NPs retained up to 88% of (223)Ra over 35days. However, in the core+2 shells NPs, the retention of (223)Ra and its daughter, (211)Pb, was improved to >99.9% over 27days. Additionally, the retention of (225)Ra/(225)Ac parents was >99.98% and ~80% for the (221)Fr and (213)Bi daughters over 35days for the core+2 shells NPs.

CONCLUSIONS

The in vitro retention of both parents and daughters results suggests that LaPO4 NPs are potentially effective carriers of radium isotopes.

摘要

引言

靶向α治疗（TAT）有潜力杀死微转移灶，同时对周围健康组织造成的附带损害最小。体内发生器放射性核素，如（223）Ra、（225）Ra和（225）Ac，因其在衰变过程中发射多个α粒子，在放射治疗应用中具有特殊意义。利用能够保留母体放射性同位素及其子产物的合适载体，对于将放射性同位素有效递送至肿瘤部位同时减轻整体体内放射毒性很重要。在这项工作中，合成了含有（223）Ra或（225）Ra/（225）Ac的LaPO4核和核+2壳纳米颗粒（NPs）（在核表面沉积有两层冷LaPO4的NPs），并研究了NPs在体外对母体和子体的保留情况。

方法

通过在适度加热下使1当量的La（NO3）3与几微居里的（223）Ra或（225）Ra/（225）Ac与1当量的三聚磷酸钠（TPP）在水溶液中反应，合成核LaPO4 NPs，并通过膜透析进行纯化。还合成了核壳NPs，在放射性核上沉积一层（核+1壳）和两层（核+2壳）冷LaPO4层。然后通过透射电子显微镜（TEM）和粉末X射线衍射（XRD）对NPs进行表征。使用γ射线光谱法研究了体外从NPs释放的放射性母体和子体的鉴定和定量。

结果

XRD和TEM分析表明，NPs结晶为斜方硫铁矿相，核和核+2壳的平均直径分别为3.4和6.3nm。核LaPO4 NPs在35天内保留了高达88%的（223）Ra。然而，在核+2壳NPs中，（223）Ra及其子体（211）Pb的保留率在27天内提高到>99.9%。此外，对于核+2壳NPs，（225）Ra/（225）Ac母体的保留率>99.98%，（221）Fr和（213）Bi子体在35天内的保留率约为80%。