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    Research Grants Awarded

    Multimodality-Enabled Optical Imaging Agents For Breast Cancers

    Grant Mechanism:
    Postdoctoral Fellowships

    Scientific Abstract:
    Breast cancer is one of the most frequently diagnosed malignancies and the second leading cause of cancer deaths in female Americans. Imaging techniques that improve breast cancer early detection, localization, and evaluation of therapy are targeted as major breakthrough in combating the disease. Among these techniques, specialized MRI and optical imaging have become increasingly important. Multimodality imaging systems, especially those combining optical and magnetic methods, have become increasingly important in the fight against breast cancers. A combination of specialized MRI and fluorescence imaging greatly enhance their overall performance to offer many significant advantages and benefits. Such approaches combine the high-resolution and high sensitivity of optical techniques with the non-invasiveness and clinical feasibility of MRI. However, the multimodality imaging approach requires the development of high-performance contrast agents amenable to in vitro and in vivo uses. The proposed project is for the designated Fellow to play a major and leading role in the development of a new class of multifunctional imaging agents by implanting or coating magnetic elements on the newly discovered benign (nontoxic) carbon quantum dots. Focus will be on the experimental validation of their potential as multimodality-enabled optical imaging agents in the detection, diagnostics, and treatment of breast cancers. It is hypothesized that a novel class of multimodality-enabled optical imaging agents may be developed by coupling MRI-sensitive structures (e.g., Gadolinium) with the newly discovered fluorescent carbon quantum dots, and that these imaging agents offer some unique configurations and properties ideal to applications in the detection, diagnostics, and treatment of breast cancers and beyond. The purpose of this project is to provide the Fellow with sufficient resources to put such an idea to experimental tests for successful outcomes. A number of unique advantages for these imaging agents are envisaged, such as: (a) the compactness because the overall ?composite? carbon quantum dots remain small in size (less than 10 nm in diameter); (b) the flexibility and control in the ?implanting/doping? of MRI-sensitive structures, either completely inside the carbon nanoparticles, on their surface, or as true composites, and (c) the amenabilty to covalent conjugation with targeting molecules. The Specific Aims of the project are for the Fellow (1) to explore and demonstrate a novel class of multifunctional imaging agents targeting multimodality breast cancer imaging applications. The created particles will undergo systematic characterizations of their structures and properties, including optical spectroscopic characterization for a comparison of fluorescence properties between the dots with and without the MRI-sensitive structures, SQUID for the study of the magnetic properties; (2) to perform evaluation and validation studies with selected imaging agent configurations, using in vitro and in vivo imaging experiments with animal and human breast cancer models. The research plan calls for the coupling of MRI-sensitive structures with the fluorescent carbon quantum dots in two different approaches: (1) during the production of precursor carbon nanoparticles; and (2) using wet-chemical coating either before or after the formation of carbon quantum dots. For each of the two approaches, two somewhat different methods/strategies will be used. It is recognized that the multimodality (optical/magnetic, for example) imaging agents for the detection, diagnostics, and treatment of breast cancers require specific targeting of breast cancer cells or biomarkers. Thus, a focus of this project is also on the conjugation of the multimodality-enabled fluorescent carbon quantum dots with 4-hydroxy-tamoxifen and estradiol, which are known to target estrogen receptors.

    Lay Abstract:
    Multimodality imaging systems, especially those combining optical and magnetic methods to take advantages in better temporal and spatial resolutions, respectively, have become increasingly important in the fight against breast cancers. The proposed project is for the designated Fellow to play a major and leading role in the development of a new class of multifunctional imaging agents by implanting or coating magnetic elements on the newly discovered benign (nontoxic) carbon quantum dots, especially the experimental validation on their potentials as multimodality-enabled optical imaging agents in the detection, diagnostics, and treatment of breast cancers. WHY MULTIMODALITY? Optical (fluorescence) imaging and MRI have their respective advantages in a complementary fashion, so that their combination offers substantial enhancement in both sensitivity and accuracy beyond a simple addition (or ?one-plus-one equals three or more?). To facilitate such a multimodality approach is the development of imaging agents that provide excellent contrasts and other properties for both techniques. WHY THE PROJECT (PURSUED BY THE DESIGNATED FELLOW)? Since great promises of semiconductor quantum dots in fluorescence imaging of cancers (especially breast cancers) have been demonstrated in vitro and in vivo, in the development of multimodality imaging agents, extensive recent efforts have been centered on the magnetic doping of fluorescent semiconductor quantum dots. However, even without the widely held serious concerns on the potential toxicity problems associated with the semiconductor quantum dots because of their mostly required contents of heavy metal elements (such as cadmium), there are also significant technical issues with the desired magnetic doing. The research program that hosts the designated Fellow has recently discovered and developed carbon quantum dots, which are based on the unique surface properties of small carbon particles and contain no heavy metals or other toxic elements at all. In this project the Fellow will play a major and leading role in the development of a new class of multimodality-enabled optical imaging agents by introducing magnetic elements into the benign (nontoxic) fluorescent carbon quantum dots, offering an innovative and unique solution to the needs for multimodality breast cancer imaging. There are many significant advantages with the use of carbon quantum dots as the platform for multimodality imaging agents, such as carbon being an abundant and nontoxic element, the physicochemical and photochemical stability of the dots, and the predicted low costs in the eventual large-scale production of the imaging agents. For dual-modality imaging a number of unique advantages for these agents are envisaged, such as: (a) the compactness because the overall ?composite? carbon quantum dots remain small in size (less than 10 nm in diameter); (b) the flexibility and control in the ?implanting/doping? of magnetic elements, either completely inside the carbon nanoparticles, on the surface, or true composites, depending on the different preparation techniques; and (c) amenable to covalent conjugation with targeting molecules and species for physico-chemically and photochemically stable imaging agents specific to breast cancers. TIMELY BENEFITS OF THE PROJECT TO PATIENTS AND THE POPULATION AT LARGE: The Aims of the project are to explore and demonstrate (various synthesis techniques and characterization experiments) a new class of multifunctional imaging agents targeting multimodality breast cancer imaging applications, and to perform various evaluation and validation studies on the imaging agents. The expected outcomes are the knowledge and technology for a new class of multimodality-enabled optical imaging agents for specifically targeted early detection, diagnostics, and treatment of breast cancers. While the project itself does not include a path to clinical uses, the results thus obtained will stimulate the pursuit of such applications by the research collaborators and others in the medical community, which ultimately benefits the breast cancer patients and the population at large.