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      Radionuclide Imaging of Apoptosis in Malignancies: Promise and Pitfalls of 99mTc-Hynic-rh-Annexin V Imaging

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          Abstract

          Radionuclide detection of apoptosis with of 99mTc-Hynic-rh-Annexin V scintigraphy is an effective tool for in vivo visualisation and monitoring of apoptosis in various malignant tumour. Early therapy-induced increase of the tumour tracer uptake correlates with favourable outcome, whereas stable or decreased uptake correlates with stable disease or tumour progression. Therefore sequential 99mTc-Hynic-rh-Annexin V scintigraphy could be used to predict therapy outcome on a patient-to-patient basis within 48 hours after the start of treatment. However, moderate tumour-to-background ratio and therapy-induced changes in normal tissues could confound image analysis. To assure accurate interpretation of Annexin V scans, the awareness of the biophysiological and biochemical properties contributing to the tracer distribution is essential. In with manuscript we discuss the patterns of Annexin V tumour uptake and illustrate the most frequent pitfalls associated with Annexin V imaging in correlation with CT and MRI imaging.

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          Most cited references28

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          Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure.

          Apoptosis is a programmed, physiological mode of cell death that plays an important role in tissue homeostasis. Understanding of the basic mechanisms that underlie apoptosis will point to potentially new targets of therapeutic treatment of diseases that show an imbalance between cell proliferation and cell loss. In order to conduct such research, techniques and tools to reliably identify and enumerate death by apoptosis are essential. This review focuses on a novel technique to detect apoptosis by targeting for the loss of phospholipid asymmetry of the plasma membrane. It was recently shown that loss of plasma membrane asymmetry is an early event in apoptosis, independent of the cell type, resulting in the exposure of phosphatidylserine (PS) residues at the outer plasma membrane leaflet. Annexin V was shown to interact strongly and specifically with PS and can be used to detect apoptosis by targeting for the loss of plasma membrane asymmetry. Labeled annexin V can be applied both in flow cytometry and in light microscopy in both vital and fixed material by using appropriate protocols. The annexin V method is an extension to the current available methods. This review describes the basic mechanisms underlying the loss of membrane asymmetry during apoptosis and discusses the novel annexin V-binding assay.
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            A matter of life and death.

            We propose that deregulation of proliferation, together with a reduction in apoptosis, creates a platform that is both necessary and can be sufficient for cancer. The secondary traits of diverse neoplasms are a consequence of cell proliferation, tissue expansion, and other outcomes of this platform.
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              Apoptosis, autophagy, and more.

              Cell death has been subdivided into the categories apoptosis (Type I), autophagic cell death (Type II), and necrosis (Type III). The boundary between Type I and II has never been completely clear and perhaps does not exist due to intrinsic factors among different cell types and the crosstalk among organelles within each type. Apoptosis can begin with autophagy, autophagy can end with apoptosis, and blockage of caspase activity can cause a cell to default to Type II cell death from Type I. Furthermore, autophagy is a normal physiological process active in both homeostasis (organelle turnover) and atrophy. "Autophagic cell death" may be interpreted as the process of autophagy that, unlike other situations, does not terminate before the cell collapses. Since switching among the alternative pathways to death is relatively common, interpretations based on knockouts or inhibitors, and therapies directed at controlling apoptosis must include these considerations.
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                Author and article information

                Journal
                Clin Med Oncol
                101467911
                Clinical Medicine. Oncology
                Libertas Academica
                1177-9314
                2008
                25 March 2008
                : 2
                : 319-325
                Affiliations
                [1 ]Department of Nuclear Medicine, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
                [2 ]Department of Radiotherapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
                [3 ]Department of Nuclear Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
                Author notes
                Correspondence: Dr. R.A. Valdes Olmos, Nuclear Medicine, Netherlands Cancer Institute Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Tel: +31205122289; Fax: +31205122225; Email: r.valdes@ 123456nki.nl
                Article
                cmo-2-2008-319
                3161632
                21892293
                7c911488-8038-4d62-9a5a-78f8479ad4b5
                © 2008 the author(s), publisher and licensee Libertas Academica Ltd.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license http://creativecommons.org/licenses/by/3.0/).

                History
                Categories
                Methodology

                Oncology & Radiotherapy
                imaging oncology,apoptosis,99mtc-hynic-rh-annexin-v
                Oncology & Radiotherapy
                imaging oncology, apoptosis, 99mtc-hynic-rh-annexin-v

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