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      Prolonged Dye Release from Mesoporous Silica-Based Imaging Probes Facilitates Long-Term Optical Tracking of Cell Populations In Vivo

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          A molecular imaging primer: modalities, imaging agents, and applications.

          Molecular imaging is revolutionizing the way we study the inner workings of the human body, diagnose diseases, approach drug design, and assess therapies. The field as a whole is making possible the visualization of complex biochemical processes involved in normal physiology and disease states, in real time, in living cells, tissues, and intact subjects. In this review, we focus specifically on molecular imaging of intact living subjects. We provide a basic primer for those who are new to molecular imaging, and a resource for those involved in the field. We begin by describing classical molecular imaging techniques together with their key strengths and limitations, after which we introduce some of the latest emerging imaging modalities. We provide an overview of the main classes of molecular imaging agents (i.e., small molecules, peptides, aptamers, engineered proteins, and nanoparticles) and cite examples of how molecular imaging is being applied in oncology, neuroscience, cardiology, gene therapy, cell tracking, and theranostics (therapy combined with diagnostics). A step-by-step guide to answering biological and/or clinical questions using the tools of molecular imaging is also provided. We conclude by discussing the grand challenges of the field, its future directions, and enormous potential for further impacting how we approach research and medicine.
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            Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe.

            A first-in-human clinical trial of ultrasmall inorganic hybrid nanoparticles, "C dots" (Cornell dots), in patients with metastatic melanoma is described for the imaging of cancer. These renally excreted silica particles were labeled with (124)I for positron emission tomography (PET) imaging and modified with cRGDY peptides for molecular targeting. (124)I-cRGDY-PEG-C dot particles are inherently fluorescent, containing the dye, Cy5, so they may be used as hybrid PET-optical imaging agents for lesion detection, cancer staging, and treatment management in humans. However, the clinical translation of nanoparticle probes, including quantum dots, has not kept pace with the accelerated growth in minimally invasive surgical tools that rely on optical imaging agents. The safety, pharmacokinetics, clearance properties, and radiation dosimetry of (124)I-cRGDY-PEG-C dots were assessed by serial PET and computerized tomography after intravenous administration in patients. Metabolic profiles and laboratory tests of blood and urine specimens, obtained before and after particle injection, were monitored over a 2-week interval. Findings are consistent with a well-tolerated inorganic particle tracer exhibiting in vivo stability and distinct, reproducible pharmacokinetic signatures defined by renal excretion. No toxic or adverse events attributable to the particles were observed. Coupled with preferential uptake and localization of the probe at sites of disease, these first-in-human results suggest safe use of these particles in human cancer diagnostics.
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              Bright and stable core-shell fluorescent silica nanoparticles.

              A class of highly fluorescent and photostable core-shell nanoparticles from a modified Stober synthesis in the size range of 20-30 nm is described. These nanoparticles are monodisperse in solution, 20 times brighter, and more photostable than their constituent fluorophore, and are amenable to specific labeling of biological macromolecules for bioimaging experiments. The photophysical characteristics of the encapsulated fluorophores differ from their solution properties. This raises the possibility of tuning nanoparticle structure toward enhanced radiative properties, making them an attractive material platform for a diverse range of applications.
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                Author and article information

                Journal
                Small
                Small
                Wiley
                16136810
                March 2016
                March 2016
                January 25 2016
                : 12
                : 12
                : 1578-1592
                Affiliations
                [1 ]Pharmaceutical Sciences Laboratory; Faculty of Science and Engineering; Åbo Akademi University; FI-20520 Turku Finland
                [2 ]Laboratory of Physical Chemistry; Faculty of Science and Engineering; Åbo Akademi University; FI-20500 Turku Finland
                [3 ]Department of Clinical Science; University of Bergen; Norway
                [4 ]Turku Centre for Biotechnology; University of Turku and Åbo Akademi University; P.O. Box 123 FI-20521 Turku Finland
                [5 ]Cell Biology; Faculty of Science and Engineering; Åbo Akademi University; FI-20520 Turku Finland
                [6 ]Laboratory of Biophysics; Faculty of Medicine; University of Turku; FI-20520 Turku Finland
                [7 ]Department of Biomedical Engineering; Institute for Complex Molecular Systems; Technical University of Eindhoven; 2612 Eindhoven The Netherlands
                Article
                10.1002/smll.201503392
                26807551
                5895387e-c23a-4b54-9ae7-0e7aab287f1f
                © 2016

                http://doi.wiley.com/10.1002/tdm_license_1.1

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