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      Amino Acid PET – An Imaging Option to Identify Treatment Response, Posttherapeutic Effects, and Tumor Recurrence?

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          Abstract

          Routine diagnostics and treatment monitoring in patients with primary and secondary brain tumors is usually based on contrast-enhanced standard MRI. However, the capacity of standard MRI to differentiate neoplastic tissue from non-specific posttreatment effects may be limited particularly after therapeutic interventions such as radio- and/or chemotherapy or newer treatment options, e.g., immune therapy. Metabolic imaging using PET may provide relevant additional information on tumor metabolism, which allows a more accurate diagnosis especially in clinically equivocal situations, particularly when radiolabeled amino acids are used. Amino acid PET allows a sensitive monitoring of a response to various treatment options, the early detection of tumor recurrence, and an improved differentiation of tumor recurrence from posttherapeutic effects. In the past, this method had only limited availability due to the use of PET tracers with a short half-life, e.g., C-11. In recent years, however, novel amino acid PET tracers labeled with positron emitters with a longer half-life (F-18) have been developed and clinically validated, which allow a more efficient and cost-effective application. These developments and the well-documented diagnostic performance of PET using radiolabeled amino acids suggest that its application continues to spread and that this technique may be available as a routine diagnostic tool for several indications in the field of neuro-oncology.

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          Most cited references45

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          Brain tumors.

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            Response criteria for phase II studies of supratentorial malignant glioma.

            We suggest "new" response criteria for phase II studies of supratentorial malignant glioma and favor rigorous criteria similar to those in medical oncology, with important modifications. Four response categories are proposed: complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Response in this scheme is based on major changes in tumor size on the enhanced computed tomographic (CT) or magnetic resonance imaging (MRI) scan. Scan changes are interpreted in light of steroid use and neurologic findings. We advocate careful patient selection, emphasize pitfalls in the assessment of response, and suggest guidelines to minimize misinterpretations of response.
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              Bevacizumab plus irinotecan in recurrent glioblastoma multiforme.

              The prognosis for patients with recurrent glioblastoma multiforme is poor, with a median survival of 3 to 6 months. We performed a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irinotecan. This phase II trial included two cohorts of patients. The initial cohort, comprising 23 patients, received bevacizumab at 10 mg/kg plus irinotecan every 2 weeks. The dose of irinotecan was based on the patient's anticonvulsant: Patients taking enzyme-inducing antiepileptic drugs (EIAEDs) received 340 mg/m2, and patients not taking EIAEDs received 125 mg/m2. After this regimen was deemed safe and effective, the irinotecan schedule was changed to an accepted brain tumor regimen of four doses in 6 weeks, in anticipation of a phase III randomized trial of irinotecan versus irinotecan and bevacizumab. The second cohort, comprising 12 patients, received bevacizumab 15 mg/kg every 21 days and irinotecan on days 1, 8, 22, and 29. Each cycle was 6 weeks long and concluded with patient evaluations, including magnetic resonance imaging. The 6-month progression-free survival among all 35 patients was 46% (95% CI, 32% to 66%). The 6-month overall survival was 77% (95% CI, 64% to 92%). Twenty of the 35 patients (57%; 95% CI, 39% to 74%) had at least a partial response. One patient developed a CNS hemorrhage, which occurred in his 10th cycle. Four patients developed thromboembolic complications (deep venous thrombosis and/or pulmonary emboli). Bevacizumab and irinotecan is an effective treatment for recurrent glioblastoma multiforme and has moderate toxicity.
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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/321976
                URI : http://frontiersin.org/people/u/362963
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                28 July 2016
                2016
                : 7
                : 120
                Affiliations
                [1] 1Department of Neurology, University of Cologne , Cologne, Germany
                [2] 2Institute of Neuroscience and Medicine, Forschungszentrum Jülich , Jülich, Germany
                [3] 3Center of Integrated Oncology (CIO), University of Cologne , Cologne, Germany
                [4] 4Department of Nuclear Medicine, University of Aachen , Aachen, Germany
                Author notes

                Edited by: Pamela Zyman New, Montreal Neurological Institute and Hospital, USA

                Reviewed by: Arjun Sahgal, University of Toronto, Canada; Maria Caffo, University of Messina, Italy

                *Correspondence: Norbert Galldiks, n.galldiks@ 123456fz-juelich.de

                Specialty section: This article was submitted to Neuro-Oncology, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2016.00120
                4963389
                27516754
                58eac9c8-4cdc-4da0-a091-a3430427d1e5
                Copyright © 2016 Galldiks and Langen.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 11 March 2016
                : 18 July 2016
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 65, Pages: 7, Words: 5509
                Categories
                Neuroscience
                Perspective

                Neurology
                fet pet,met pet,fdopa pet,radiolabeled amino acids,pseudoprogression,pseudoresponse,radiation necrosis

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