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  • 1
    Keywords: SURVIVAL ; tumor ; MODEL ; DIAGNOSIS ; QUANTIFICATION ; IMPACT ; chemotherapy ; SOFT-TISSUE SARCOMAS ; PREDICTION ; FEASIBILITY ; F-18-FDG ; FDG ; F-18-FDG PET ; compartment modeling
    Abstract: F-18-FDG kinetics are quantified by a 2-tissue-compartment model. The routine use of dynamic PET is limited because of this modality's 1-h acquisition time. We evaluated shortened acquisition protocols up to 0-30 min regarding the accuracy for data analysis with the 2-tissue-compartment model. Methods: Full dynamic series for 0-60 min were analyzed using a 2-tissue-compartment model. The time-activity curves and the resulting parameters for the model were stored in a database. Shortened acquisition data were generated from the database using the following time intervals: 0-10, 0-16, 0-20, 0-25, and 0-30 min. Furthermore, the impact of adding a 60-min uptake value to the dynamic series was evaluated. The datasets were analyzed using dedicated software to predict the results of the full dynamic series. The software is based on a modified support vector machines (SVM) algorithm and predicts the compartment parameters of the full dynamic series. Results: The SVM-based software provides user-independent results and was accurate at predicting the compartment parameters of the full dynamic series. If a squared correlation coefficient of 0.8 (corresponding to 80% explained variance of the data) was used as a limit, a shortened acquisition of 0-16 min was accurate at predicting the 60-min 2-tissue-compartment parameters. If a limit of 0.9 (90% explained variance) was used, a dynamic series of at least 0-20 min together with the 60-min uptake values is required. Conclusion: Shortened acquisition protocols can be used to predict the parameters of the 2-tissue-compartment model. Either a dynamic PET series of 0-16 min or a combination of a dynamic PET/CT series of 0-20 min and a 60-min uptake value is accurate for analysis with a 2-tissue-compartment model
    Type of Publication: Journal article published
    PubMed ID: 21321263
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  • 2
    Keywords: CANCER ; proliferation ; cell cycle ; gene expression ; SOFT-TISSUE SARCOMAS ; PET ; FDG ; gene array ; F-18-FDG KINETICS ; PET DATA
    Abstract: INTRODUCTION: Glucose transporters and hexokinases determine the kinetics of 2-deoxy-2-[(18)F]fluoro-D: -glucose (FDG). However, the genes controlling these proteins are not independent and may be modulated from other biological processes, e.g., like angiogenesis and proliferation. The impact of cell-proliferation-related genes on the FDG kinetics was assessed in colorectal tumors in this study. METHODS: Patients with primary colorectal tumors (n = 25) were examined with positron emission tomography and FDG within 2 days prior to surgery. Tissue specimens were obtained from the colorectal tumor and the normal colon by surgery and gene expression was assessed using gene arrays. RESULTS: Overall, an increase of the expression of proliferation associated genes was observed by a factor of 2-5.3 for the colorectal tumors as compared with the normal colon. Correlation analysis revealed an impact of cdk2 on K1, thus directing to a modulation of the FDG uptake into the cells. The correlations were generally higher for the FDG influx as compared with the standardized uptake value (SUV). The influx was mainly correlated with proliferation inhibiting genes (cyclin G2, cdk inhibitor 1 C, cdk inhibitor 2B). It was possible to predict the expression of cyclin D2 using a multiple linear regression function and the parameters of the FDG kinetics with r = 0.67. Using a group based analysis it was possible to demonstrate, that tumors with an SUV 〉12 are associated with a high expression of cyclin D2 in the colorectal tumors. If the gene expression data for cyclin D1, cyclin G2, cdk2, cdk6 and cdk inhibtor 2B were used, the overall FDG uptake as measured by the SUV could be predicted with r = 0.75. CONCLUSIONS: The results suggest that the FDG kinetics is modulated by proliferation associated genes. Especially K1, the parameter for the FDG transport into the cells, is modulated by cdk2. Tumors with a SUV exceeding 12 have usually a higher expression of cyclin D2. The parameters of the FDG kinetics can be used to predict the expression of proliferation associated genes individually.
    Type of Publication: Journal article published
    PubMed ID: 21153447
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  • 3
    Keywords: ANGIOGENESIS ; tumor ; GENE-EXPRESSION ; POSITRON-EMISSION-TOMOGRAPHY ; PET ; F-18-FDG ; MDA-MB-231 breast cancer cells ; FDG ; BONE METASTASES ; cell invasion ; INTEGRIN ALPHA-V-BETA-3 ; Cilengitide ; PRIMARY CHEMOTHERAPY ; RGD PEPTIDES ; SIALOPROTEIN
    Abstract: The purpose of this study was the assessment of the feasibility of dynamic positron emission tomography (PET) studies with fluorine-18 fluorodeoxyglucose (F-18-FDG) to quantify effects of the cyclic Arg-Gly-Asp peptide cilengitide, which targets the alpha v beta 3 and alpha v beta 5 integrin receptors in rats with breast cancer bone metastases. Rats were inoculated with MDA-MB-231 breast cancer cells, followed by the development of lytic lesions in the hind leg. Rats with lytic lesions were treated with cilengitide five times weekly on a continuous basis from days 30 to 55 after tumor cell inoculation. Dynamic PET studies with 18F-FDG were performed in untreated (n=9), controlled (n=4) and treated rats (n=6). The data were assessed using learning-machine two-tissue compartmental analysis. The F-18-FDG kinetic parameters obtained by two-tissue compartmental model learning-machine showed significant differences when individual parameters were compared between the control group and treated animals. Quantitative assessment of the tracer kinetics and the application of classification analysis to the data provided us with evidence to identify those tumors that demonstrated effect of cilengitide treatment. The transport rate K1 and the phosphorylation rate k3 were significantly different (P=0.033 and 0.038, respectively). Classification analysis based on support vector machines ranking feature elimination of the combination of PET parameters revealed an overall accuracy of 80.0% between treated animals and the control group. We were able to identify 83.3% treated animals compared with the control group based on k2 and VB. In conclusion, the results revealed that cilengitide treatment of experimental breast cancer bone metastases had a significant therapeutics impact on F-18-FDG kinetics
    Type of Publication: Journal article published
    PubMed ID: 21512659
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