Author: Sixiang Shi
Publisher:
Published: 2016
Total Pages: 0
ISBN-13:
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Molecular imaging, the "visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems", has played an important role in cancer diagnosis. With the advances in nanotechnology, nanomaterials have emerged as a promising candidate for molecular imaging, due to their unique properties. Graphene is one of the most promising nanomaterials, which is intrinsically useful for drug loading and photo therapy of cancer. However, in vivo biodistribution and tumor targeting with graphene nanomaterial is an underexplored area. In this dissertation, we designed a radiolabeled antibody conjugated reduced graphene oxide (RGO) nanoplatform for in vivo positron emission tomography (PET) and tumor vasculature targeting. Excellent tumor uptake was achieved with 64Cu-NOTA-RGO-TRC105, compared to non-targeted RGO conjugate (64Cu-NOTA-RGO). Various experiments were performed, demonstrating that the vasculature targeting is highly specific (Chapter 2). In the following study, graphene oxide (GO), another subtype of graphene nanomaterials, was conjugated with anti-angiogenesis protein vascular endothelial growth factor 121 (VEGF121) to further validate the active targeting and imaging of graphene nanomaterials. Significantly enhanced tumor accumulation (>8 %ID/g) as well as high tumor-to-muscle contrast was achieved, showing great potential for future tumor targeted imaging (Chapter 3). Although traditional chelators are generally utilized in radiolabeling and PET imaging of nanomaterials, a novel chelator-free radiolabeling approach was designed with graphene nanoparticles (Chapter 4). The chelator-free radiolabeled RGO possesses decent labeling efficiency and enhanced in vivo radiostability over NOTA-chelated RGO, making it especially suitable for nanoparticle-based radiolabeling. Bypassing the use of chemical chelator, the intrinsically radiolabeled nanoparticles are able to maintain the native pharmacokinetics, and therefore more accurately reflect the distribution in vivo. Besides graphene, layered double hydroxide (LDH) and molybdenum disulfide (MoS2) nanoparticles were also employed for chelator-free radiolabeling and examined in vivo (Chapter 5 and 6). Excellent tumor uptake and in vivo integrity were observed, further validating the potential of chelator-free labeling in molecular imaging. Taking advantaging of molecular imaging and nanotechnology, a promising multifunctional nanoplatform can be designed for in vivo cancer management. Further efforts are necessary to thoroughly understand the in vivo behavior of nanoparticles and apply them in clinic
