99mTc-Bisphosphonate-Iron Oxide Nanoparticle Conjugates for Dual-Modality Biomedical Imaging

被引:159
作者
de Rosales, Rafael Torres Martin [1 ]
Tavare, Richard [1 ]
Glaria, Arnaud [1 ]
Varma, Gopal [1 ]
Protti, Andrea [1 ]
Blower, Philip J. [1 ]
机构
[1] Kings Coll London, St Thomas Hosp, Div Imaging Sci & Biomed Engn, London SE1 7EH, England
基金
英国工程与自然科学研究理事会; 英国惠康基金;
关键词
CU-64-LABELED MAGNETIC NANOPARTICLES; POSITRON-EMISSION-TOMOGRAPHY; SURFACE FUNCTIONALIZATION; CONTRAST; PET; PLATFORM; PROBES; BONE; BISPHOSPHONATES; DIAGNOSIS;
D O I
10.1021/bc100483k
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The combination of radionuclide-based imaging modalities such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) with magnetic resonance imaging (MRI) is likely to become the next generation of clinical scanners. Hence, there is a growing interest in the development of SPECT- and PET-MRI agents. To this end, we report a new class of dual-modality imaging agents based on the conjugation of radiolabeled bisphosphonates (BP) directly to the surface of superparamagnetic iron oxide (SPIO) nanopartides. We demonstrate the high potential of BP-iron oxide conjugation using Tc-99m-dipicolylamine(DPA)-alendronate, a BP-SPECT agent, and Endorem/Feridex, a liver MRI contrast agent based on SPIO. The labeling of SPIOs with Tc-99m-DPA-alendronate can be performed in one step at room temperature if the SPIO is not coated with an organic polymer. Heating is needed if the nanoparticles are coated, as long as the coating is weakly bound as in the case of dextran in Endorem. The size of the radiolabeled Endorem (Tc-99m-DPA-ale-Endorem) was characterized by TEM (5 nm, Fe3O4 core) and DLS (106 +/- 60 nm, Fe3O4 core + dextran). EDX, Dittmer-Lester, and radiolabeling studies demonstrate that the BP is bound to the nanoparticles and that it binds to the Fe3O4 cores of Endorem, and not its dextran coating. The bimodal imaging capabilities and excellent stability of these nanoparticles were confirmed using MRI and nanoSPECT-CT imaging, showing that Tc-99m and Endorem co-localize in the liver and spleen In Vivo, as expected for particles of the composition and size of Tc-99m-DPA-ale-Endorem. To the best of our knowledge, this is the first example of radiolabeling SPIOs with BP conjugates and the first example of radiolabeling SPIO nanoparticles directly onto the surface of the iron oxide core, and not its coating. This work lays down the basis for a new generation of SPECT/PET-MR imaging agents in which the BP group could be used to attach functionality to provide targeting, stealth/stability, and radionuclides to Fe3O4 nanoparticles using very simple methodology readily amenable to GMP.
引用
收藏
页码:455 / 465
页数:11
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