10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Kinetic Modeling Application to 18F-fluoroethylcholine Positron Emission Tomography in Patients with Primary and Recurrent Prostate Cancer Using Two-tissue Compartmental Model

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Although 18F-fludeoxyglucose-positron emission tomography (PET) is the most applied diagnostic method in tumor staging, its role in prostate cancer (PCA) is limited because glucose metabolism tends to be low unless PCA has high Gleason score. Alternatively, choline PET was introduced as a valuable imaging method. Kinetic analysis of PET acquisition has increasingly gained momentum as an investigative tool because it provides a non-invasive approach to obtain kinetic and metabolic data from tissues of interest including transport and metabolism of the administered material. In this regard, we sought to apply it in 18F-fluoroethylcholine (FECH)-PET/computed tomography (CT) in patients with PCA. 64 patients, the mean age 69 (range: 47-87 years) with primary/recurrent PCA were encompassed. They underwent 18F-FECH-PET started with a dynamic acquisition using a 20-frame each 30 s over the prostate region and followed at 1 h post-injection by a static whole body imaging. The kinetic evaluation of the data was performed using the software package PMOD (PMOD Technologies Ltd., Zürich, Switzerland). Significant increase in mean values for K1, K3, FD, standardized uptake value (SUV) and global influx in tumor tissue versus normal tissue ( P < 0.05). Moderate but significant correlation ( r: 0.28, P = 0.023) between SUV and K1. By contrast, no correlation between SUV and K3 ( r: −0.08, P = 0.79). In patients with recurrent tumors, there is no significant difference in all kinetic parameters and SUV ( P > 0.1) between the different types of recurrences. The kinetic analysis of dynamic FECH-PET provides a novel method in primary PCA diagnosis and could be of potential value in the delineation of tumor focus.

          Related collections

          Most cited references26

          • Record: found
          • Abstract: found
          • Article: not found

          Malignant transformation alters membrane choline phospholipid metabolism of human mammary epithelial cells.

          Transduction of mitogenic signals in cells can be mediated by molecules derived from the synthesis and breakdown of the major membrane phospholipid, phosphotidylcholine. Studies were performed on human mammary epithelial cells in culture to understand the impact of malignant transformation and progression on membrane phospholipid metabolism. In the model system used here, phosphocholine levels and total choline-containing phospholipid metabolite levels increased with progression from normal to immortalized to oncogene-transformed to tumor-derived cells. These changes occurred independently of cell doubling time. A "glycerophosphocholine to phosphocholine switch" was apparent with immortalization. This alteration in phenotype of increased phosphocholine relative to glycerophosphocholine was observed in oncogene-transformed and for all human breast tumor cell lines analyzed. The results demonstrate that progression of human mammary epithelial cells from normal to malignant phenotype is associated with altered membrane choline phospholipid metabolism.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Alterations of choline phospholipid metabolism in ovarian tumor progression.

            Recent characterization of abnormal phosphatidylcholine metabolism in tumor cells by nuclear magnetic resonance (NMR) has identified novel fingerprints of tumor progression that are potentially useful as clinical diagnostic indicators. In the present study, we analyzed the concentrations of phosphatidylcholine metabolites, activities of phosphocholine-producing enzymes, and uptake of [methyl-14C]choline in human epithelial ovarian carcinoma cell lines (EOC) compared with normal or immortalized ovary epithelial cells (EONT). Quantification of phosphatidylcholine metabolites contributing to the 1H NMR total choline resonance (3.20-3.24 ppm) revealed intracellular [phosphocholine] and [total choline] of 2.3 +/- 0.9 and 5.2 +/- 2.4 nmol/10(6) cells, respectively, with a glycerophosphocholine/phosphocholine ratio of 0.95 +/- 0.93 in EONT cells; average [phosphocholine] was 3- to 8-fold higher in EOC cells (P < 0.0001), becoming the predominant phosphatidylcholine metabolite, whereas average glycerophosphocholine/phosphocholine values decreased significantly to < or =0.2. Two-dimensional (phosphocholine/total choline, [total choline]) and (glycerophosphocholine/total choline, [total choline]) maps allowed separate clustering of EOC from EONT cells (P < 0.0001, 95% confidence limits). Rates of choline kinase activity in EOC cells were 12- to 24-fold higher (P < 0.03) than those in EONT cells (basal rate, 0.5 +/- 0.1 nmol/10(6) cells/h), accounting for a consistently elevated (5- to 15-fold) [methyl-14C]choline uptake after 1-hour incubation (P < 0.0001). The overall activity of phosphatidylcholine-specific phospholipase C and phospholipase D was also higher ( approximately 5-fold) in EOC cells, suggesting that both biosynthetic and catabolic pathways of the phosphatidylcholine cycle likely contribute to phosphocholine accumulation. Evidence of abnormal phosphatidylcholine metabolism might have implications in EOC biology and might provide an avenue to the development of noninvasive clinical tools for EOC diagnosis and treatment follow-up.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              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.
                Bookmark

                Author and article information

                Journal
                World J Nucl Med
                World J Nucl Med
                WJNM
                World Journal of Nuclear Medicine
                Medknow Publications & Media Pvt Ltd (India )
                1450-1147
                1607-3312
                Sep-Dec 2013
                : 12
                : 3
                : 101-110
                Affiliations
                [1 ]Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg
                [2 ]Department of Nuclear Medicine and Radiology, Knappschaft Hospital, 66280 Sulzbach, Germany
                Author notes
                Address for correspondence: Dr. Mustafa Takesh, University Heidelberg, Department of Nuclear Medicine, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. E-mail: takesh@ 123456stud.uni-heidelberg.de
                Article
                WJNM-12-101
                10.4103/1450-1147.136734
                4145150
                3e41405c-e5fb-40fc-a10b-cbad36059293
                Copyright: © World Journal of Nuclear Medicine

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Original Article

                Radiology & Imaging
                choline-positron emission tomography,kinetic modeling,prostate cancer
                Radiology & Imaging
                choline-positron emission tomography, kinetic modeling, prostate cancer

                Comments

                Comment on this article