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Biomedicines, Volume 4, Issue 4 (December 2016)

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Research

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Open AccessArticle Glioma FMISO PET/MR Imaging Concurrent with Antiangiogenic Therapy: Molecular Imaging as a Clinical Tool in the Burgeoning Era of Personalized Medicine
Biomedicines 2016, 4(4), 24; doi:10.3390/biomedicines4040024
Received: 15 September 2016 / Revised: 27 October 2016 / Accepted: 29 October 2016 / Published: 31 October 2016
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Abstract
The purpose of this article is to provide a focused overview of the current use of positron emission tomography (PET) molecular imaging in the burgeoning era of personalized medicine in the treatment of patients with glioma. Specifically, we demonstrate the utility of PET
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The purpose of this article is to provide a focused overview of the current use of positron emission tomography (PET) molecular imaging in the burgeoning era of personalized medicine in the treatment of patients with glioma. Specifically, we demonstrate the utility of PET imaging as a tool for personalized diagnosis and therapy by highlighting a case series of four patients with recurrent high grade glioma who underwent 18F-fluoromisonidazole (FMISO) PET/MR (magnetic resonance) imaging through the course of antiangiogenic therapy. Three distinct features were observed from this small cohort of patients. First, the presence of pseudoprogression was retrospectively associated with the absence of hypoxia. Second, a subgroup of patients with recurrent high grade glioma undergoing bevacizumab therapy demonstrated disease progression characterized by an enlarging nonenhancing mass with newly developed reduced diffusion, lack of hypoxia, and preserved cerebral blood volume. Finally, a reduction in hypoxic volume was observed concurrent with therapy in all patients with recurrent tumor, and markedly so in two patients that developed a nonenhancing reduced diffusion mass. This case series demonstrates how medical imaging has the potential to influence personalized medicine in several key aspects, especially involving molecular PET imaging for personalized diagnosis, patient specific disease prognosis, and therapeutic monitoring. Full article
(This article belongs to the Special Issue Molecular Imaging as a Tool for Personalized Medicine)
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Review

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Open AccessFeature PaperReview Personalized Dosimetry for Radionuclide Therapy Using Molecular Imaging Tools
Biomedicines 2016, 4(4), 25; doi:10.3390/biomedicines4040025
Received: 12 September 2016 / Revised: 7 November 2016 / Accepted: 8 November 2016 / Published: 15 November 2016
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Abstract
For treatment of systemic malignancies, when external radiation therapy is not applicable, radionuclide therapy can be an alternative. In this form of therapy, radionuclides are administered to the patient, often in a form where the radionuclide is labelled to a molecule that plays
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For treatment of systemic malignancies, when external radiation therapy is not applicable, radionuclide therapy can be an alternative. In this form of therapy, radionuclides are administered to the patient, often in a form where the radionuclide is labelled to a molecule that plays the active part in the localization of the tumor. Since the aim is to impart lethal damage to tumor cells while maintaining possible side-effects to normal tissues at tolerable levels, a proper and accurate personalized dosimetry should be a pre-requisite. In radionuclide therapy, there is a need to measure the distribution of the radiopharmaceutical in vivo, as well as its re-distribution over time, in order estimate the total energy released in radioactive decays and subsequent charged-particle interactions, governing the absorbed dose to different organs and tumors. Measurements are usually performed by molecular imaging, more specifically planar and SPECT (Single-Photon Emission Computed Tomography) imaging, combined with CT. This review describes the different parts in the dosimetry chain of radionuclide therapy. Emphasis is given to molecular imaging tools and the requirements for determining absorbed doses from quantitative planar and SPECT images. As example solutions to the different problems that need to be addressed in such a dosimetric chain, we describe our tool, Lundadose, which is a set of methods that we have developed for personalized dosimetry. Full article
(This article belongs to the Special Issue Molecular Imaging as a Tool for Personalized Medicine)
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Open AccessReview The Strategies to Homogenize PET/CT Metrics: The Case of Onco-Haematological Clinical Trials
Biomedicines 2016, 4(4), 26; doi:10.3390/biomedicines4040026
Received: 3 September 2016 / Revised: 6 November 2016 / Accepted: 8 November 2016 / Published: 15 November 2016
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Abstract
Positron emission tomography (PET) has been a widely used tool in oncology for staging lymphomas for a long time. Recently, several large clinical trials demonstrated its utility in therapy management during treatment, paving the way to personalized medicine. In doing so, the traditional
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Positron emission tomography (PET) has been a widely used tool in oncology for staging lymphomas for a long time. Recently, several large clinical trials demonstrated its utility in therapy management during treatment, paving the way to personalized medicine. In doing so, the traditional way of reporting PET based on the extent of disease has been complemented by a discrete scale that takes in account tumour metabolism. However, due to several technical, physical and biological limitations in the use of PET uptake as a biomarker, stringent rules have been used in clinical trials to reduce the errors in its evaluation. Within this manuscript we will describe shortly the evolution in PET reporting, examine the main errors in uptake measurement, and analyse which strategy the clinical trials applied to reduce them. Full article
(This article belongs to the Special Issue Molecular Imaging as a Tool for Personalized Medicine)
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Open AccessReview Complementary Approaches to Existing Target Based Drug Discovery for Identifying Novel Drug Targets
Biomedicines 2016, 4(4), 27; doi:10.3390/biomedicines4040027
Received: 30 August 2016 / Revised: 16 November 2016 / Accepted: 17 November 2016 / Published: 21 November 2016
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Abstract
In the past decade, it was observed that the relationship between the emerging New Molecular Entities and the quantum of R&D investment has not been favorable. There might be numerous reasons but few studies stress the introduction of target based drug discovery approach
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In the past decade, it was observed that the relationship between the emerging New Molecular Entities and the quantum of R&D investment has not been favorable. There might be numerous reasons but few studies stress the introduction of target based drug discovery approach as one of the factors. Although a number of drugs have been developed with an emphasis on a single protein target, yet identification of valid target is complex. The approach focuses on an in vitro single target, which overlooks the complexity of cell and makes process of validation drug targets uncertain. Thus, it is imperative to search for alternatives rather than looking at success stories of target-based drug discovery. It would be beneficial if the drugs were developed to target multiple components. New approaches like reverse engineering and translational research need to take into account both system and target-based approach. This review evaluates the strengths and limitations of known drug discovery approaches and proposes alternative approaches for increasing efficiency against treatment. Full article
(This article belongs to the Special Issue Molecular Imaging as a Tool for Personalized Medicine)
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Open AccessReview Cellular and Molecular Preconditions for Retinal Pigment Epithelium (RPE) Natural Reprogramming during Retinal Regeneration in Urodela
Biomedicines 2016, 4(4), 28; doi:10.3390/biomedicines4040028
Received: 19 October 2016 / Revised: 26 November 2016 / Accepted: 26 November 2016 / Published: 1 December 2016
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Abstract
Many regeneration processes in animals are based on the phenomenon of cell reprogramming followed by proliferation and differentiation in a different specialization direction. An insight into what makes natural (in vivo) cell reprogramming possible can help to solve a number of biomedical problems.
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Many regeneration processes in animals are based on the phenomenon of cell reprogramming followed by proliferation and differentiation in a different specialization direction. An insight into what makes natural (in vivo) cell reprogramming possible can help to solve a number of biomedical problems. In particular, the first problem is to reveal the intrinsic properties of the cells that are necessary and sufficient for reprogramming; the second, to evaluate these properties and, on this basis, to reveal potential endogenous sources for cell substitution in damaged tissues; and the third, to use the acquired data for developing approaches to in vitro cell reprogramming in order to obtain a cell reserve for damaged tissue repair. Normal cells of the retinal pigment epithelium (RPE) in newts (Urodela) can change their specialization and transform into retinal neurons and ganglion cells (i.e., actualize their retinogenic potential). Therefore, they can serve as a model that provides the possibility to identify factors of the initial competence of vertebrate cells for reprogramming in vivo. This review deals mainly with the endogenous properties of native newt RPE cells themselves and, to a lesser extent, with exogenous mechanisms regulating the process of reprogramming, which are actively discussed. Full article
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