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      18F-FIMP: a LAT1-specific PET probe for discrimination between tumor tissue and inflammation

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          Abstract

          Positron emission tomography (PET) imaging can assist in the early-phase diagnostic and therapeutic evaluation of tumors. Here, we report the radiosynthesis, small animal PET imaging, and biological evaluation of a L-type amino acid transporter 1 (LAT1)-specific PET probe, 18F-FIMP. This probe demonstrates increased tumor specificity, compared to existing tumor-specific PET probes ( 18F-FET, 11C-MET, and 18F-FDG). Evaluation of probes by in vivo PET imaging, 18F-FIMP showed intense accumulation in LAT1-positive tumor tissues, but not in inflamed lesions, whereas intense accumulation of 18F-FDG was observed in both tumor tissues and in inflamed lesions. Metabolite analysis showed that 18F-FIMP was stable in liver microsomes, and mice tissues (plasma, urine, liver, pancreas, and tumor). Investigation of the protein incorporation of 18F-FIMP showed that it was not incorporated into protein. Furthermore, the expected mean absorbed dose of 18F-FIMP in humans was comparable or slightly higher than that of 18F-FDG and indicated that 18F-FIMP may be a safe PET probe for use in humans. 18F-FIMP may provide improved specificity for tumor diagnosis, compared to 18F-FDG, 18F-FET, and 11C-MET. This probe may be suitable for PET imaging for glioblastoma and the early-phase monitoring of cancer therapy outcomes.

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          Value of 11C-methionine PET in imaging brain tumours and metastases.

          (11)C-methionine (MET) is the most popular amino acid tracer used in PET imaging of brain tumours. Because of its characteristics, MET PET provides a high detection rate of brain tumours and good lesion delineation. This review focuses on the role of MET PET in imaging cerebral gliomas. The Introduction provides a clinical overview of what is important in primary brain tumours, recurrent brain tumours and brain metastases. The indications for radiotherapy and the results and problems arising after chemoradiotherapy in relation to imaging (pseudoprogression or radionecrosis) are discussed. The working mechanism, scan interpretation and quantification possibilities of MET PET are then explained. A literature overview is given of the role of MET PET in primary gliomas (diagnostic accuracy, grading, prognosis, assessment of tumour extent, biopsy and radiotherapy planning), in brain metastases, and in the differentiation between tumour recurrence and radiation necrosis. Finally, MET PET is compared to other nuclear imaging possibilities in brain tumour imaging.
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            FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models.

            Although FDG uptake is closely related to the expression of the glucose transporter (GLUT) in malignant tumors, such a relationship has not been fully investigated in inflammatory lesions. The aim of our study was to determine the expression of GLUT subtypes in experimental inflammatory lesions and to compare the results with those in malignant tumors in relation to FDG accumulation. Rats were inoculated with a suspension of Staphylococcus aureus or allogenic hepatoma cells (KDH-8) into the left calf muscle. Five days after S. aureus inoculation (n = 9) and 14 d after KDH-8 inoculation (n = 11), [(14)C]FDG was injected intravenously and its accumulation in the infectious and tumor tissues was determined as the percentage activity of the injected dose per gram of tissue (%ID/g). The expression of glucose transporters (GLUT-1 to GLUT-5) was investigated by immunostaining the infectious tissues (n = 6) and the tumor tissues (n = 6). Immunohistochemical grading was assessed semiquantitatively by 5 observers. The [(14)C]FDG uptake was significantly higher in the tumor lesion than in the inflammatory lesion (2.04 +/- 0.38 %ID/g vs. 0.72 +/- 0.15 %ID/g; P < 0.0001). The tumor and inflammatory tissues highly expressed GLUT-1 and GLUT-3. The GLUT-1 expression level was significantly higher in the tumor tissue than in the inflammatory tissue (P < 0.05). The results based on our models showed a high FDG uptake and high GLUT-1 expression level not only in the tumor lesion but also in the inflammatory lesion. The higher GLUT-1 expression level in the tumor lesion may partially explain the higher FDG accumulation in the tumor than in the inflammatory lesion.
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              Normal variants, artefacts and interpretative pitfalls in PET imaging with 18-fluoro-2-deoxyglucose and carbon-11 methionine.

              Interpretation of studies from all imaging modalities requires a knowledge of the possible pitfalls that may occur due to normal variation, artefacts and processes which may mimic pathology. The applications and use of not only 18-fluoro-2-deoxyglucose but also l-[methyl-(11)C] methionine positron emission tomography (PET) are widening and it is timely that the currently recognised interpretative pitfalls are reviewed as the number of dedicated PET scanners and coincidence gamma cameras increases.
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                Author and article information

                Contributors
                yywata@riken.jp
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                31 October 2019
                31 October 2019
                2019
                : 9
                : 15718
                Affiliations
                [1 ]Laboratory for Pathophysiological and Health Science, RIKEN Center for Biosystems Dynamics Research and Center for Life Science Technologies, Kobe, Hyogo 650-0047 Japan
                [2 ]Novel PET Diagnostics Laboratory, RIKEN Innovation Center, Hyogo, 650-0047 Japan
                [3 ]Laboratory for Labeling Chemistry, RIKEN Center for Biosystems Dynamics Research and Center for Life Science Technologies, Kobe, Hyogo 650-0047 Japan
                Author information
                http://orcid.org/0000-0001-9778-5841
                Article
                52270
                10.1038/s41598-019-52270-x
                6823354
                31673030
                474009cf-0cb2-4e82-9c86-05af78b1e647
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 6 June 2019
                : 10 October 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/100009619, Japan Agency for Medical Research and Development (AMED);
                Funded by: FundRef https://doi.org/10.13039/501100001700, Ministry of Education, Culture, Sports, Science and Technology (MEXT);
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized
                cancer imaging,diagnostic markers
                Uncategorized
                cancer imaging, diagnostic markers

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