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      The Potential Benefit by Application of Kinetic Analysis of PET in the Clinical Oncology

      review-article
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      ISRN Oncology
      International Scholarly Research Network

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          Abstract

          PET is an appropriate method to display the functional activities in target tissue using many types of traces. The visual assessment of PET images plus the semiquantitative parameter (SUV) are the main diagnostic standards considered in identifying the malignant lesion. However, these standards lack occasionally the proper specificity and/or sensitivity. That emphasizes the importance of considering supplemental diagnostic criteria such as the kinetic parameter. The latter gives the way to image the ongoing metabolic processes within the target tissue as well as to identify the alterations occurring at the microscale level before they become observable in the conventional PET-imaging. The importance of kinetic analysis of PET imaging has increased with newly developed PET devices that offer images of good quality and high spatial resolution. In this paper, we highlighted the potential contribution of kinetic analysis in improving the diagnostic accuracy in intracranial tumour, lung tumour, liver tumour, colorectal tumour, bone and soft tissue tumours, and prostate cancer. Moreover, we showed that the appropriate therapy monitoring can be best achieved after considering the kinetic parameters. These promising results indicate that the kinetic analysis of PET imaging may become an essential part in preclinical and clinical molecular imaging as well.

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          Most cited references75

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          Choline transport for phospholipid synthesis.

          Choline is an essential nutrient for all cells because it plays a role in the synthesis of the membrane phospholipid components of the cell membranes, as a methyl-group donor in methionine metabolism as well as in the synthesis of the neurotransmitter acetylcholine. Choline deficiency affects the expression of genes involved in cell proliferation, differentiation, and apoptosis, and it has been associated with liver dysfunction and cancer. Abnormal choline transport and metabolism have been implicated in a number of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Therefore, the study of choline transport and the characteristics of choline transporters are of central importance to understanding the mechanisms that underlie membrane integrity and cell signaling in such disorders. Kinetic studies with radiolabeled choline and inhibitors distinguish three systems for choline transport: (i) low-affinity facilitated diffusion, (ii) high-affinity, Na+-dependent transport, and (iii) intermediate-affinity, Na+-independent transport. It is only recently, however, that the proteins having transport characteristics of at least one of these systems have been identified. They include (i) polyspecific organic cation transporters (OCTs) with low affinity for choline, (ii) high-affinity choline transporters (CHT1s), and (iii) intermediate-affinity choline transporter-like (CTL1) proteins. CHT1 and CTL1 but not OCT transporters are selectively inhibited with hemicholinium-3 and essentially display characteristics of specialized transporters for targeted choline metabolism. CHT1 is abundant in neurons and almost exclusively supplies choline for acetyl-choline synthesis. The focus here is more on newly-discovered CTL1 choline transporters. They are expressed in different organisms and cell types, apparently not for the biosynthesis of acetylcholine but for the production of the most abundant metabolite of choline, the membrane lipid phosphatidylcholine.
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            Tumor cell metabolism imaging.

            Molecular imaging of tumor metabolism has gained considerable interest, since preclinical studies have indicated a close relationship between the activation of various oncogenes and alterations of cellular metabolism. Furthermore, several clinical trials have shown that metabolic imaging can significantly impact patient management by improving tumor staging, restaging, radiation treatment planning, and monitoring of tumor response to therapy. In this review, we summarize recent data on the molecular mechanisms underlying the increased metabolic activity of cancer cells and discuss imaging techniques for studies of tumor glucose, lipid, and amino acid metabolism.
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              18F-FDOPA PET imaging of brain tumors: comparison study with 18F-FDG PET and evaluation of diagnostic accuracy.

              We evaluated the amino acid and glucose metabolism of brain tumors by using PET with 3,4-dihydroxy-6-(18)F-fluoro-l-phenylalanine ((18)F-FDOPA) and (18)F-FDG. Eighty-one patients undergoing evaluation for brain tumors were studied. Initially, 30 patients underwent PET with (18)F-FDOPA and (18)F-FDG within the same week. Tracer kinetics in normal brain and tumor tissues were estimated. PET uptake was quantified by use of standardized uptake values and the ratio of tumor uptake to normal hemispheric tissue uptake (T/N). In addition, PET uptake with (18)F-FDOPA was quantified by use of ratios of tumor uptake to striatum uptake (T/S) and of tumor uptake to white matter uptake. The accuracies of (18)F-FDOPA and (18)F-FDG PET were determined by comparing imaging data with histologic findings and findings of clinical follow-up of up to 31 mo (mean, 20 mo). To further validate the accuracy of (18)F-FDOPA PET, (18)F-FDOPA PET was performed with an additional 51 patients undergoing brain tumor evaluation. Tracer uptake in tumors on (18)F-FDOPA scans was rapid, peaking at approximately 15 min after intravenous injection. Tumor uptake could be distinguished from that of the striatum by the difference in peak times. Both high-grade and low-grade tumors were well visualized with (18)F-FDOPA. The sensitivity for identifying tumors was substantially higher with (18)F-FDOPA PET than with (18)F-FDG PET at comparable specificities, as determined by simple visual inspection, especially for the assessment of low-grade tumors. Using receiver-operating-characteristic curve analysis, we found the optimal threshold for (18)F-FDOPA to be a T/S of greater than 1.0 (sensitivity, 96%; specificity, 100%) or a T/N of greater than 1.3 (sensitivity, 96%; specificity, 86%). The high diagnostic accuracy of (18)F-FDOPA PET at these thresholds was confirmed with the additional 51 patients (a total of 81 patients: sensitivity, 98%; specificity, 86%; positive predictive value, 95%; negative predictive value, 95%). No significant difference in tumor uptake on (18)F-FDOPA scans was seen between low-grade and high-grade tumors (P = 0.40) or between contrast-enhancing and nonenhancing tumors (P = 0.97). Radiation necrosis was generally distinguishable from tumors on (18)F-FDOPA scans (P < 0.00001). (18)F-FDOPA PET was more accurate than (18)F-FDG PET for imaging of low-grade tumors and evaluating recurrent tumors. (18)F-FDOPA PET may prove especially useful for imaging of recurrent low-grade tumors and for distinguishing tumor recurrence from radiation necrosis.
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                Author and article information

                Journal
                ISRN Oncol
                ISRN Oncol
                ISRN.ONCOLOGY
                ISRN Oncology
                International Scholarly Research Network
                2090-5661
                2090-567X
                2012
                26 December 2012
                : 2012
                : 349351
                Affiliations
                Nuclear Medicine Department, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
                Author notes

                Academic Editors: S. Honoré and T. Yokoe

                Article
                10.5402/2012/349351
                3541563
                23326682
                cb68ab40-7407-47fc-9925-23ac62ca07d3
                Copyright © 2012 Mustafa Takesh.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 4 November 2012
                : 25 November 2012
                Categories
                Review Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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