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      Ocular Biodistribution Studies Using Molecular Imaging

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          Abstract

          Classical methodologies used in ocular pharmacokinetics studies have difficulties to obtain information about topical and intraocular distribution and clearance of drugs and formulations. This is associated with multiple factors related to ophthalmic physiology, as well as the complexity and invasiveness intrinsic to the sampling. Molecular imaging is a new diagnostic discipline for in vivo imaging, which is emerging and spreading rapidly. Recent developments in molecular imaging techniques, such as positron emission tomography (PET), single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI), allow obtaining reliable pharmacokinetic data, which can be translated into improving the permanence of the ophthalmic drugs in its action site, leading to dosage optimisation. They can be used to study either topical or intraocular administration. With these techniques it is possible to obtain real-time visualisation, localisation, characterisation and quantification of the compounds after their administration, all in a reliable, safe and non-invasive way. None of these novel techniques presents simultaneously high sensitivity and specificity, but it is possible to study biological procedures with the information provided when the techniques are combined. With the results obtained, it is possible to assume that molecular imaging techniques are postulated as a resource with great potential for the research and development of new drugs and ophthalmic delivery systems.

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          Most cited references145

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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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            Molecular imaging in drug development.

            Molecular imaging can allow the non-invasive assessment of biological and biochemical processes in living subjects. Such technologies therefore have the potential to enhance our understanding of disease and drug activity during preclinical and clinical drug development, which could aid decisions to select candidates that seem most likely to be successful or to halt the development of drugs that seem likely to ultimately fail. Here, with an emphasis on oncology, we review the applications of molecular imaging in drug development, highlighting successes and identifying key challenges that need to be addressed for successful integration of molecular imaging into the drug development process.
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              Pharmacokinetic aspects of retinal drug delivery

              Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                16 May 2019
                May 2019
                : 11
                : 5
                : 237
                Affiliations
                [1 ]Pharmacy Department, University Hospital of Santiago de Compostela (SERGAS), 15706 Santiago de Compostela, Spain; ana.castro.balado@ 123456gmail.com (A.C.-B.); crismondelo1@ 123456gmail.com (C.M.-G.); miguel.gonzalez.barcia@ 123456sergas.es (M.G.-B.); irene.zarra.ferro@ 123456sergas.es (I.Z.-F.)
                [2 ]Pharmacology Group, Health Research Institute Santiago Compostela (IDIS), 15706 Santiago de Compostela, Spain
                [3 ]Department of Pharmacology, Pharmacy and Pharmaceutical Technology and Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain; francisco.otero@ 123456usc.es
                [4 ]Nuclear Medicine Department, University Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela, 15706 Santiago de Compostela, Spain; alvaro.ruibal.morell@ 123456sergas.es
                [5 ]Molecular Imaging Group, Health Research Institute Santiago Compostela (IDIS), 15706 Santiago de Compostela, Spain
                Author notes
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0001-5168-114X
                https://orcid.org/0000-0001-9030-2253
                https://orcid.org/0000-0002-7322-2195
                https://orcid.org/0000-0002-7348-7337
                Article
                pharmaceutics-11-00237
                10.3390/pharmaceutics11050237
                6572242
                31100961
                a74d3a83-fb32-43cc-a7bf-c8d1d5b5cde6
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 14 April 2019
                : 07 May 2019
                Categories
                Review

                ocular biodistribution,ocular permanence,molecular imaging,pet,spect,mri

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