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      PET-MR and SPECT-MR multimodality probes: Development and challenges

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          Abstract

          Positron emission tomography (PET)-magnetic resonance (MR) or single photon emission computed tomography (SPECT)-MR hybrid imaging is being used in daily clinical practice. Due to its advantages over stand-alone PET, SPECT or MR imaging, in many areas such as oncology, the demand for hybrid imaging techniques is increasing dramatically. The use of multimodal imaging probes or biomarkers in a single molecule or particle to characterize the imaging subjects such as disease tissues certainly provides us with more accurate diagnosis and promotes therapeutic accuracy. A limited number of multimodal imaging probes are being used in preclinical and potential clinical investigations. The further development of multimodal PET-MR and SPECT-MR imaging probes includes several key elements: novel synthetic strategies, high sensitivity for accurate quantification and high anatomic resolution, favourable pharmacokinetic profile and target-specific binding of a new probe. This review thoroughly summarizes all recently available and noteworthy PET-MR and SPECT-MR multimodal imaging probes including small molecule bimodal probes, nano-sized bimodal probes, small molecular trimodal probes and nano-sized trimodal probes. To the best of our knowledge, this is the first comprehensive overview of all PET-MR and SPECT-MR multimodal probes. Since the development of multimodal PET-MR and SPECT-MR imaging probes is an emerging research field, a selection of 139 papers were recognized following the literature review. The challenges for designing multimodal probes have also been addressed in order to offer some future research directions for this novel interdisciplinary research field.

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          Most cited references118

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          Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials.

          The interactions of nanoparticles with the soft surfaces of biological systems like cells play key roles in executing their biomedical functions and in toxicity. The discovery or design of new biomedical functions, or the prediction of the toxicological consequences of nanoparticles in vivo, first require knowledge of the interplay processes of the nanoparticles with the target cells. This article focusses on the cellular uptake, location and translocation, and any biological consequences, such as cytotoxicity, of the most widely studied and used nanoparticles, such as carbon-based nanoparticles, metallic nanoparticles, and quantum dots. The relevance of the size and shape, composition, charge, and surface chemistry of the nanoparticles in cells is considered. The intracellular uptake pathways of the nanoparticles and the cellular responses, with potential signaling pathways activated by nanoparticle interactions, are also discussed. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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            The ability to track the distribution and differentiation of progenitor and stem cells by high-resolution in vivo imaging techniques would have significant clinical and research implications. We have developed a cell labeling approach using short HIV-Tat peptides to derivatize superparamagnetic nanoparticles. The particles are efficiently internalized into hematopoietic and neural progenitor cells in quantities up to 10-30 pg of superparamagnetic iron per cell. Iron incorporation did not affect cell viability, differentiation, or proliferation of CD34+ cells. Following intravenous injection into immunodeficient mice, 4% of magnetically CD34+ cells homed to bone marrow per gram of tissue, and single cells could be detected by magnetic resonance (MR) imaging in tissue samples. In addition, magnetically labeled cells that had homed to bone marrow could be recovered by magnetic separation columns. Localization and retrieval of cell populations in vivo enable detailed analysis of specific stem cell and organ interactions critical for advancing the therapeutic use of stem cells.
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                Author and article information

                Journal
                Theranostics
                Theranostics
                thno
                Theranostics
                Ivyspring International Publisher (Sydney )
                1838-7640
                2018
                29 November 2018
                : 8
                : 22
                : 6210-6232
                Affiliations
                [1 ]Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 59 Nanyang Drive, Singapore 636921.
                [2 ]Karolinska Institutet, Department of Clinical Neuroscience, S-171 76, Stockholm, Sweden.
                [3 ]Department of Clinical Pharmacology and Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, A-1090, Vienna, Austria.
                [4 ]Center for Health and Bioresources, Biomedical Systems, AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
                [5 ]Cixi Institute of Biomedical Engineering, Ningbo Institute of Industrial Technology and Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, P.R. China, 315201.
                [6 ]Department of Nuclear Medicine and Molecular Imaging, Radiological Sciences Division, Singapore General Hospital, Outram Road, Singapore 169608.
                [7 ]Duke-NUS Medical School, 8 College Road, Singapore 169857.
                Author notes
                ✉ Corresponding author: Chang-Tong Yang Email: yangct@ 123456ntu.edu.sg ; yang.changtong@ 123456sgh.com.sg ; chmyct@ 123456yahoo.com ; Tel: (65)6326-5666.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                thnov08p6210
                10.7150/thno.26610
                6299694
                30613293
                d41a6056-6ebc-4f80-9195-52f78cfad997
                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 11 April 2018
                : 8 June 2018
                Categories
                Review

                Molecular medicine
                bimodality imaging probe,pet-mr,spect-mr,contrast agent,radioligand
                Molecular medicine
                bimodality imaging probe, pet-mr, spect-mr, contrast agent, radioligand

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