Fe / Fe> Nano-particles In Target MR / SPECT Imaging And Photothermal Therapy

With the development of the personalized medicine, multimodality imaging by use of the combination the different molecular imaging technologies, has widely used in clinical cancer diagnosis to overcome limitations of the single imaging mode. Among the biomedical imaging techniques, magnetic resonance（MR） imaging has the high spatial resolution（several tens of micrometers） and soft tissue contrast, but suffers from limited sensitivity. Single photon emission computed tomography（SPECT） imaging is highly sensitive but is low spatial resolution and lack of the anatomical information. It has been widely used for quantitative in vivo monitoring of living subjects. The combination of MR and SPECT imaging can provide the complementary information with the high sensitivity and high resolution to visualize the molecular events more accurately in vivo. The use of MR/SPECT contrast agents can help to clarify images and detect tumor by enhancing the contrast between cancerous and normal tissues particularly on the early stage of cancer development.In this dissertation, a multifunctional nanotheranostic agent is developed for in vivo MR/SPECT guided highly-effective targeting photothermal therapy（PTT）.Chapter 1. A general introduction to synthesis of nanoparticles, molecular imaging means, tumor diagnosis and theraoy methods are presented. We also describe the applications of nanoparticles in oncology and highlight the new trend of theranostic nanomaterials. Finally, basis and main contents of this dissertation are listed.Chapter 2. We design Fe@Fe₃O₄ nanoparticles that possess a good dispersion, low toxicity, good biocompatibility and high saturation magnetization, high photothermal conversion efficiency. The cyclic c（RGDy K） peptide directly labeled by ¹²⁵ I conjugated PEGylated Fe@Fe₃O₄ nanoparticles（RGD-PEG-MNPs） with the average hydrodynamic diameter of 40 nm as a novel multifunctional platform were developed for targeting MR and SPECT imaging guided photothermal therapy in vivo. On the αvβ₃-positive U87 MG glioblastoma xenograft model, the signals of tumor from T₂-weighted MR and SPECT imaging were much higher than those in the blocking group at 6 h intravenous injection（i.v.） of RGD-PEG-MNPs and ¹²⁵ I radiolabeled RGD-PEG-MNPs, respectively. The pharmacokinetics and biodistribution were analyzed quantitatively by SPECT imaging ex vivo. The facts suggested that RGD-PEG-MNPs should exhibit the excellent targeting property and low reticuloendothelial uptake. At 6 h i.v. injection of ¹²⁵I-RGD-PEG-MNPs, the maximum uptake of 6.75 ± 1.24 % of the percentage injected dose per gram（ID/g） was accumulated in tumor. At 48 h i.v., only 1.11 ± 0.21 % and 0.16 ± 0.09% ID/g of were accumulated in liver and spleen, respectively. With the guidance of MR/SPECT imaging, the multifunctional nanoparticles achieved a good photothermal therapeutic efficacy in vivo.