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  • 1
    Keywords: CANCER ; CANCER CELLS ; CELLS ; INHIBITOR ; tumor ; BLOOD ; CELL ; Germany ; KINASE ; MODEL ; PATHWAY ; imaging ; SYSTEM ; SYSTEMS ; liver ; GENE ; PROTEIN ; PROTEINS ; METABOLISM ; TUMORS ; NUCLEAR-MEDICINE ; PATIENT ; MECHANISM ; mechanisms ; protein kinase ; PROTEIN-KINASE ; treatment ; SIGNAL ; ANTITUMOR-ACTIVITY ; TARGET ; metastases ; RESECTION ; CANCER-CELLS ; positron emission tomography ; POSITRON-EMISSION-TOMOGRAPHY ; tomography ; GLUCOSE ; PET ; LIVER METASTASES ; imatinib ; SARCOMA ; nuclear medicine ; AKT ; GASTROINTESTINAL STROMAL TUMORS ; INHIBITORS ; targeting ; ONCOLOGY ; RE ; monitoring ; INCREASE ; F-18-FDG ; TRANSPORTER ; KINASE INHIBITORS ; LEVEL ; ENZYME ; NUCLEAR ; uptake ; female ; UNIT ; KINASE INHIBITOR ; FDG ; EMISSION-TOMOGRAPHY ; ANTITUMOR ACTIVITIES ; surgical resection ; SARCOMAS ; mTOR ; MEDICINE ; UPSTREAM ; PROTEIN-KINASE-B ; antitumor activity ; German ; EMISSION ; emission tomography ; CASCADE ; GIST ; m-TOR inhibitor ; positron ; protein kinase B ; treatment monitoring
    Abstract: Several mechanisms may influence the enhanced glucose uptake in cancer cells, including upregulation of glucose transporters, increase in the hexokinase activity and the protein kinase B, also called Akt, which appears to play key role in the control of glucose metabolism together with proteins which are involved in the signal cascade pathway, such as the mammalian target of rapamycin (mTOR). It has been demonstrated in patients with gastrointestinal stromal tumors (GIST) and other sarcomas who received treatment with imatinib that PET with F-18-FDG is appropriate for treatment monitoring. Data suggest that F-18-FDG monitoring may be used for monitoring not only imatinib but also other kinase inhibitors. A 36-year-old female patient with metastasized desmoplastic small round cells tumor after a broad surgical resection of the tumor area and due to related enzyme findings, was treated with the mTOR-inhibitor everolimus (Certican((R)), Novartis, Basel, Switzerland) at an initial dose of 3 x 0.5 mg per day targeting at a blood level of 〉 11 ng/ml. A baseline F-18-FDG-PET demonstrated an enhanced FDG uptake in three large liver metastases and in another metastatic lesion in the pelvic area. A dynamic F-18-FDG-PET study performed six weeks later, demonstrated non-response to the mTOR-inhibitor. Despite the antiproliferative activity of mTOR-inhibitors in experimental model systems, its antitumor activity in patients may be limited. In conclusion, F-18-FDG-PET seems to be a promising method for monitoring the therapeutic effect of mTOR-inhibitors
    Type of Publication: Journal article published
    PubMed ID: 17684580
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  • 2
    Keywords: CANCER ; EXPRESSION ; tumor ; COMBINATION ; Germany ; TYROSINE KINASE ; imaging ; screening ; CLONING ; TUMORS ; NUCLEAR-MEDICINE ; LIGAND ; FAMILY ; BASE ; DISCOVERY ; score ; TRIAL ; IDENTIFICATION ; EFFICIENT ; DATABASE ; LIGANDS ; PHARMACOKINETICS ; nuclear medicine ; TRACER ; INHIBITORS ; radiology ; RE ; SOFTWARE ; methods ; NUCLEAR ; 3D ; CRITERIA ; GA-68-DOTATOC ; docking ; SET ; MEDICINE ; modeling ; SOMATOSTATIN RECEPTOR ; IN-SILICO ; SSTR2 ; virtuals screening ; Y-90-DOTATOC THERAPY
    Abstract: New ligands are needed to improve diagnostics and treatment of SSTR2 expressing tumors. We implemented a procedure to identify ligands based on computer processing methods. A multistep procedure was used. Search entries were taken from National Cancer Institute database. Application of criteria defined by the Lipinski rules reduced the initial data set. Then a pharmacophore criterion including Lys and Trp residues was the next step of the hierarchical filtering, and the ligands considered were transformed from 2D to 3D. Finally, dedicated software was applied for docking ligand studies. Our results have shown that by virtual screening and trial docking, we identified novel ligands with better scores of docked poses compared with previously reported ligands. In conclusion, the use of a focused library that incorporates an initial probe, improved the possibility of a successful virtual screening as compared with random screening and is cost efficient by further combination of trial docking
    Type of Publication: Journal article published
    PubMed ID: 18815664
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  • 3
    Keywords: CANCER ; radiotherapy ; SURVIVAL ; tumor ; carcinoma ; Germany ; CT ; FOLLOW-UP ; imaging ; INFORMATION ; QUANTIFICATION ; SYSTEM ; SYSTEMS ; METABOLISM ; TUMORS ; ACCURACY ; SURGERY ; NUCLEAR-MEDICINE ; PATIENT ; MRI ; molecular imaging ; RECURRENCE ; POSITRON-EMISSION-TOMOGRAPHY ; HEAD ; PET ; FLOW-CYTOMETRY ; nuclear medicine ; NECK-CANCER ; molecular ; RE ; F-18-FDG ; NUCLEAR ; MASS ; RADIOPHARMACEUTICALS ; FDG-PET ; MEDICINE ; quantitative ; SCAN
    Abstract: PET and PET/CT are the procedures of choice for molecular imaging in the head and neck area. The current data of the literature show, that functional imaging with fluorine-18-deoxyglucose (F-18-FDG) provides the possibility to obtain information about the viability of malignant lesions. The use of hybrid systems, PET/CT, enables physicians to assess both, morphology and function, and achieve a high diagnostic accuracy exceeding 90%. PET with F-18-FDG is the most sensitive method to detect tumor recurrence. However, false positive results must be considered due to unspecific changes following treatment, especially radiotherapy. The use of quantitative PET scans as well as the application of a second tracer, enhance the capability of PET to assess questionable masses more accurately. Follow up examinations with PET and F-18-FDG provide data about early changes in the tumor metabolism due to chemotherapeutic treatment. Studies in patients undergoing surgery and radiotherapy demonstrated, that PET with F-18-FDG can be used for the prediction of individual survival
    Type of Publication: Journal article published
    PubMed ID: 18392219
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  • 4
    Keywords: ANGIOGENESIS ; CANCER ; EXPRESSION ; GROWTH ; GROWTH-FACTOR ; proliferation ; tumor ; CELL ; Germany ; IMAGES ; imaging ; SUPPORT ; SYSTEM ; SYSTEMS ; VOLUME ; liver ; GENE ; GENE-EXPRESSION ; GENES ; SAMPLE ; SAMPLES ; TUMORS ; TIME ; PATIENT ; IMPACT ; CYCLE ; ASSOCIATION ; gene expression ; ADHESION ; CELL-ADHESION ; positron emission tomography ; POSITRON-EMISSION-TOMOGRAPHY ; PET ; KINETICS ; MANAGEMENT ; GASTROINTESTINAL STROMAL TUMORS ; AGENT ; REGRESSION ; cell adhesion ; development ; vascular endothelial growth factor ; PROGRESS ; EMISSION-TOMOGRAPHY ; gene array ; COLORECTAL TUMORS ; FACTOR BINDING PROTEIN-3 ; INTERVENTIONS ; therapeutic ; 18F-FDG
    Abstract: Nuclear medicine procedures are the methods of choice for the assessment of the tracer kinetics in a volume over time. Fluorine-18 fluoro-deoxyglucose (F-18-FDG) is primarily a marker of tumor viability and the kinetics of F-18-FDG reflects major biological factors like angiogenesis and proliferation. The correct interpretation of F-18-FDG tracer kinetics demands the knowledge about the association of quantitative positron emission tomography (PET) data and gene expression. The use of gene arrays is helpful to obtain expression data for a large number of genes from tissue samples. However, limited data are available about quantitative F-18-FDG data and gene array results. Studies in primary liver cancer patients revealed that the F-18-FDG uptake was associated with genes related to tumor cell adhesion and tumor invasion. We noted in patients with giant cell tumors a correlation of the F-18-FDG uptake, as measured by the standardized uptake value (SUV) and the cell division cycle 2 (cdc2) gene expression. The effect of therapeutic interventions is dependent on the agent used for treatment. In gastrointestinal stromal tumors the change in F-18-FDG uptake is most likely due to an antiproliferative effect. However, this may be different in other tumor types and for other treatment protocols, therefore dedicated studies of the F-18-FDG kinetics and gene expression are needed. Based on the recent data available in colorectal tumors and gene expression, we were able to demonstrate that at least two key genes of the angiogenesis, vascular endothelial growth factor (VEGF-A) and angiopoietin-2, have a major impact on the tracer kinetics. Furthermore, regression functions for the F-18-FDG kinetics and gene expression data facilitate the calculation of parametric images of the gene expression, reflecting the spatial distribution of angiogenesis in a colorectal tumor. Currently the development of information management systems for the prediction of clinical relevant information in individual patients is in progress to retrieve the optimum on information from individual F-18-FDG patient examinations to support individualization of treatment management
    Type of Publication: Journal article published
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  • 5
    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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