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  • 1
    Keywords: SURVIVAL ; CELL ; Germany ; THERAPY ; MORTALITY ; RISK ; PATIENT ; TRANSPLANTATION ; INDUCTION ; treatment ; TRIAL ; EQUIVALENT ; DESIGN ; AGE ; leukemia ; HIGH-RISK ; LOW-RISK ; PROGENITOR CELLS ; allogeneic ; BONE-MARROW-TRANSPLANTATION ; PROGNOSTIC-SIGNIFICANCE ; STRATEGIES ; study design ; ABNORMALITIES ; RISK GROUP ; ALLOGENEIC TRANSPLANTATION ; stem cell transplantation ; STEM-CELL TRANSPLANTATION ; MULTICENTER ; COMPLETE REMISSION ; ETOPOSIDE ; PHASE-II ; ACUTE MYELOGENOUS LEUKEMIA ; acute myeloid leukemia ; DOSE CYTOSINE-ARABINOSIDE ; INDUCTION THERAPY ; INTENSIVE CHEMOTHERAPY ; MYELODYSPLASTIC SYNDROME ; NORMAL CYTOGENETICS ; POSTREMISSION THERAPY ; risk-adapted postremission therapy ; STUDY-GROUP ULM
    Abstract: The objective of the AML HD93 treatment trial was to evaluate the outcome in young adults with acute myeloid leukemia (AML) after postremission therapy was stratified according to cytogenetically defined risk. The rationales for the study design were based (i) on previous favorable results with high-dose cytarabine in AML with t(8; 21), inv/t(16q22) and in AML with normal karyotype, and ii) on encouraging results obtained in several phase II trials using autologous stem cell transplantation (SCT). Between July 1993 and January 1998, 223 eligible patients, 16 - 60 years of age with newly diagnosed AML other than French - American - British type M3/M3v, were entered into the trial. Risk groups were defined as follows: low risk: t( 8; 21) or inv/t( 16q22); intermediate risk: normal karyotype; high risk: all other chromosomal abnormalities. Following intensive double induction therapy with idarubicin, cytarabine and etoposide, all patients in complete remission (CR) received a first consolidation therapy with high-dose cytarabine and mitoxantrone ( HAM). A second consolidation therapy was stratified according to the risk group: low risk: HAM; intermediate risk: related allogeneic SCT or sequential HAM; high risk: related allogeneic or autologous SCT. Double induction therapy resulted in a high CR rate of 74.5%, and 90% of the responding patients were eligible for consolidation therapy. Survival for all 223 trial entrants was 40%, and for the 166 patients who entered CR, disease-free (DFS) and overall survival were 40 and 51% after 5 years, respectively. Within the low-, intermediate- and high-risk groups, DFS and survival after 5 years were 62.5 and 87, 40 and 49 and 17 and 26% respectively, without advantage for allogeneic transplantation in the intermediate- and high-risk groups. Postremission therapy-related mortality was 0, 7 and 14%, respectively. This study demonstrates the feasibility of cytogenetically defined risk-adapted consolidation therapy. The overall trial results are at least equivalent to those of published trials supporting the risk-adapted treatment strategy
    Type of Publication: Journal article published
    PubMed ID: 12886238
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  • 2
    Keywords: CANCER ; tumor ; carcinoma ; CLASSIFICATION ; COHORT ; DISTINCT ; GENE ; GENES ; TUMORS ; PATIENT ; prognosis ; treatment ; FREQUENCY ; SUSCEPTIBILITY ; BREAST ; DESIGN ; AGE ; BRCA1 ; OVARIAN-CANCER ; WOMEN ; MUTATION ; REPRODUCIBILITY ; p53 ; MUTATIONS ; MORPHOLOGY ; adenocarcinoma ; CARRIERS ; CANCER-RESEARCH ; SERIES ; POOR-PROGNOSIS ; FEATURES ; BRCA2 GENE ; GRADE ; MUTATION CARRIERS ; GERM-LINE MUTATIONS ; FAMILIAL BREAST-CANCER
    Abstract: Purpose: Germline mutations in the BRCA1 and BRCA2 genes confer increased susceptibility to ovarian cancer. There is evidence that tumors in carriers may exhibit a distinct distribution of pathological features, but previous studies on the pathology of such tumors have been small. Our aim was to evaluate the morphologies and immunophenotypes in a large cohort of patients with familial ovarian cancer.Experimental Design: We performed a systematic review of ovarian tumors from 178 BRCA1 mutation carriers, 29 BRCA2 mutation carriers, and 235 controls with a similar age distribution. Tumors were evaluated by four pathologists blinded to mutation status. Both morphological features and immunochemical staining for p53 and HER2 were evaluated.Results: Tumors in BRCA1 mutation carriers were more likely than tumors in age-matched controls to be invasive serous adenocarcinomas (odds ratio, 1.84; 95% confidence interval, 1.21-2.79) and unlikely to be borderline or mucinous tumors. Tumors in BRCA1 carriers were of higher grade (P 〈 0.0001), had a higher percentage solid component (P 0.001), and were more likely to stain strongly for p53 (P = 0.018). The distribution of pathological features in BRCA2 carriers was similar to that in BRCA1 carriers.Conclusions: Use of pathological features can substantially improve the targeting of predictive genetic testing. Results also suggest that BRCA1 and BRCA2 tumors are relatively. aggressive and may be expected to have poor prognosis, although this may be treatment dependent
    Type of Publication: Journal article published
    PubMed ID: 15073127
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  • 3
    Keywords: Germany ; THERAPY ; FOLLOW-UP ; DISEASE ; NEW-YORK ; PATIENT ; treatment ; AGE ; MUSCLE ; INDIVIDUALS ; MANAGEMENT ; PAIN ; STRENGTH ; SCALE ; THERAPIES ; DISABILITY ; FATIGUE ; late effects depression ; POLIO SURVIVORS ; POLIOMYELITIS ; postpolio syndrome ; SEQUELAE
    Abstract: Postpolio syndrome is defined as a clinical syndrome of new pareses in individuals who had been affected by acute paralytic poliomyelitis years before. The objective of this study was to describe neurologic and psychiatric signs of the disease. We evaluated the clinical signs and treatment of 16 patients with postpolio syndrome. Possible symptoms of depression were evaluated by the Hamilton and Geriatric Depression Scales. Postpolio syndrome manifested at a median age of 57.5 years (range 25-73) in a median of 41 years (range 16-70 years) after acute poliomyelitis. Muscles already affected during acute poliomyelitis were affected in all patients with postpolio syndrome. Six of 16 patients (37.5%) developed paresis in muscles formerly not affected by acute poliomyelitis. In eight of 15 patients (53%), depressive episodes were recognized according to the ICD-10 criteria. Symptoms of depression should be recognized in patients with postpolio syndrome and incorporated in therapy based on physiotherapy
    Type of Publication: Journal article published
    PubMed ID: 15088090
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  • 4
    Keywords: brain ; measurement ; radiotherapy ; tumor ; BLOOD ; Germany ; PERFUSION ; THERAPY ; FOLLOW-UP ; follow-up studies ; imaging ; QUANTIFICATION ; VOLUME ; TISSUE ; NUCLEAR-MEDICINE ; radiation ; PATIENT ; BLOOD-FLOW ; blood flow ; FLOW ; MRI ; SEQUENCE ; treatment ; stereotactic ; radiosurgery ; STEREOTACTIC RADIOSURGERY ; DECREASE ; metastases ; CEREBRAL-BLOOD-FLOW ; PREDICTION ; NORMAL TISSUE ; nuclear medicine ; brain metastases ; GLIOMAS ; LOBE EPILEPSY ; QUIPSS-II ; radiology ; RE ; THERAPIES ; IMAGING TECHNIQUES ; TUMOR VOLUME ; ARTERIAL ; neoplasm metastasis ; relative regional cerebral blood flow ; VOLUME MAPS
    Abstract: Rationale and Objectives: To assess if preradiation and early follow-up measurements of relative regional cerebral blood flow (rrCBF) can predict treatment outcome in patients with cerebral metastases and to evaluate rrCBF changes in tumor and normal tissue after stereotactic radiosurgery using arterial spin-labeling (ASL) and first-pass dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion MRI. Methods: In 25 patients with a total of 28 brain metastases, DSC MRI and ASL perfusion MRI using the Q2TIPS sequence were performed with a 1.5-T unit. Measurements were performed prior to and at 6 weeks. 12 weeks, and 24 weeks after stereotactic radiosurgery. Follow-up examinations were completely available in 25 patients for Q2TIPS and 17 patients with 18 metastases for DSC MRI. The rrCBF of the metastases and the normal brain tissue was determined by a region-of-interest analysis. rrCBF values were correlated with the treatment outcome that was classified according to tumor volume changes at 6 months. Results: The alteration of the rrCBF at the 6-week follow-up was highly predictive for treatment outcome. A decrease of the rrCBF value predicted tumor response correctly in all metastases for Q2TIPS and in 13 of 16 metastases for DSC MRI. The pretherapeutic rrCBF was not able to predict treatment outcome. The rrCBF values in normal brain tissue affected by radiation doses less than 0.5 Gy remained unchanged after therapy. Conclusion: These preliminary results suggest that ASL and DSC MRI techniques determining rrCBF changes in brain metastases after stereotactic radiosurgery allow the prediction of treatment outcome
    Type of Publication: Journal article published
    PubMed ID: 15087722
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  • 5
    Keywords: brain ; tumor ; Germany ; MODEL ; CLASSIFICATION ; imaging ; QUANTIFICATION ; TOOL ; TUMORS ; PATIENT ; IMPACT ; MRI ; LESIONS ; PARAMETERS ; Jun ; INVOLVEMENT ; DIFFUSION ; INFILTRATION ; RE ; BRAIN-TUMORS ; brain tumors ; PROFILES ; SIGNATURE ; CEREBRAL GLIOMAS ; Diffusion Tensor Imaging ; EXTENT ; corpus callosum ; DTI ; primary brain tumors
    Abstract: Diffusion tensor imaging (DTI) has been advocated as a promising tool for delineation of the extent of tumor infiltration by primary brain tumors. First reports show conflicting results mainly due to difficulties in reproducible determination of DTI-derived parameters. A novel method based on probabilistic voxel classification for a user-independent analysis of DTI-derived parameters is presented and tested in healthy controls and patients with primary brain tumors. The proposed quantification method proved to be highly reproducible both in healthy controls and patients. Fiber integrity in the corpus callosum (CC) was measured using this quantification method, and the profiles of fractional anisotropy (FA) provided additional information of the possible extent of infiltration of primary brain tumors when compared to conventional imaging. This yielded additional information on the nature of ambiguous contralateral lesions in patients with primary brain tumors. The results show that DTI-derived parameters can be determined reproducibly and may have a strong impact on evaluation of contralateral extent of primary brain tumors. (c) 2006 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 16478665
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  • 6
    Keywords: IN-VITRO ; Germany ; IN-VIVO ; VITRO ; VIVO ; IMAGES ; GENE ; TIME ; PATIENT ; MR ; MRI ; SEQUENCE ; SIGNAL ; MAGNETIC-RESONANCE ; MUTATION ; inactivation ; MUTATIONS ; MUSCLE ; ALPHA-SUBUNIT ; HUMAN SKELETAL-MUSCLE ; IMPLEMENTATION ; INCREASE ; technique ; correlation ; in vivo ; MR-IMAGES ; H1 ; NA+ ; HYPERKALEMIC PERIODIC PARALYSIS ; III-IV LINKER ; MYOTONIA-FLUCTUANS ; PARAMYOTONIA-CONGENITA ; POTASSIUM ; SODIUM-CHANNEL MUTATIONS
    Abstract: Background: Muscle channelopathies such as paramyotonia, hyperkalemic periodic paralysis, and potassium-aggravated myotonia are caused by gain-of-function Na+ channel mutations. Methods: Implementation of a three-dimensional radial Na-23 magnetic resonance (MR) sequence with ultra-short echo times allowed the authors to quantify changes in the total muscular Na-23 signal intensity. By this technique and T2-weighted H-1 MRI, the authors studied whether the affected muscles take up Na+ and water during episodes of myotonic stiffness or of cold- or exercise-induced weakness. Results: A 22% increase in the Na-23 signal intensity and edema-like changes on T2-weighted H-1 MR images were associated with cold-induced weakness in all 10 paramyotonia patients; signal increase and weakness disappeared within 1 day. A 10% increase in Na-23, but no increase in the T2-weighted H-1 signal, occurred during cold- or exercise-induced weakness in seven hyperkalemic periodic paralysis patients, and no MR changes were observed in controls or exercise-induced stiffness in six potassium-aggravated myotonia patients. Measurements on native muscle fibers revealed provocation-induced, intracellular Na+ accumulation and membrane depolarization by -41 mV for paramyotonia, by -30 mV for hyperkalemic periodic paralysis, and by -20 mV for potassium-aggravated myotonia. The combined in vivo and in vitro approach showed a close correlation between the increase in Na-23 MR signal intensity and the membrane depolarization (r = 0.92). Conclusions: The increase in the total Na-23 signal intensity reflects intracellular changes, the cold-induced Na+ shifts are greatest and osmotically relevant in paramyotonia patients, and even osmotically irrelevant Na+ shifts can be detected by the implemented Na-23 MR technique
    Type of Publication: Journal article published
    PubMed ID: 16931510
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  • 7
    Keywords: BLOOD ; Germany ; MODEL ; PERFUSION ; DIAGNOSIS ; IMAGES ; QUANTIFICATION ; VOLUME ; PATIENT ; BLOOD-FLOW ; blood flow ; FLOW ; MR ; MRI ; SIGNAL ; magnetic resonance imaging ; AGE ; WOMEN ; MEN ; MUSCLE ; PARAMETERS ; SKELETAL-MUSCLE ; ULTRASONOGRAPHY ; KINETICS ; sensitivity ; specificity ; BIOPSY ; ultrasound ; INCREASE ; replenishment kinetics ; analysis ; methods ; MYOPATHY ; muscle perfusion ; replenishment kinetics of microbubbles ; Sensitivity and Specificity ; EVALUATE ; UNIT ; myopathies ; MR-IMAGES ; contrast-enhanced ultrasound ; BIOPSIES ; DERMATOMYOSITIS ; INFLAMMATORY MYOPATHIES ; POLYMYOSITIS ; MYOSITIS ; SKELETAL-MUSCLE PERFUSION
    Abstract: Objective To evaluate prospectively contrast-enhanced ultrasound (CEUS) in patients suspected of having dermatomyositis or polymyositis. Methods In 35 patients (23 women, 12 men; mean age, 51 years +/- 16 years) who were suspected of having dermatomyositis or polymyositis, perfusion in clinically affected skeletal muscles was quantified with contrast-enhanced intermittent power Doppler ultrasound. By applying a modified model that analyzed the replenishment kinetics of microbubbles, the perfusion-related parameters blood flow, local blood volume and blood flow velocity were measured. Findings were compared with muscle biopsy appearances and with the results of MRI that was performed with a 1.5-Tesla unit. Receiver operating characteristic analysis was performed and optimum thresholds for diagnosis of myositis were determined. Results Eleven patients had histologically confirmed dermatomyositis or polymyositis and showed significantly higher blood flow velocity (P = .01 for dermato- and P 〈 .001 for polymyositis), blood flow (P 〈 .001 for dermato- and polymyositis), and blood volume (P = .007 for dermato- and P 〈 .001 for polymyositis) on contrast-enhanced ultrasound than those who did not have myositis. An increase in signal intensity on T2-weighted MR images was found in all patients with myositis. MRI had a sensitivity, specificity, positive (PPV), and negative predicting values (NPV) of 100%, 88%, 77%, and 100% for diagnosis of myositis, respectively. CEUS blood flow was the best ultrasound measure for diagnosis of dermato- or polymyositis with sensitivity, specificity, PPV, and NPV of 73%, 91%, 80%, and 88%, respectively. Conclusions Increased skeletal muscle perfusion measured by CEUS could serve as an additional measurer for the diagnosis of an inflammatory myopathy
    Type of Publication: Journal article published
    PubMed ID: 17219033
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  • 8
    Keywords: EXPRESSION ; SURVIVAL ; CELL ; Germany ; KINASE ; imaging ; NEW-YORK ; PATIENT ; ACTIVATION ; MARKER ; prognosis ; QUALITY ; TYPE-1 ; MAGNETIC-RESONANCE ; magnetic resonance imaging ; FIBER COMPOSITION ; BREAST-CANCER ; NO ; PERFORMANCE ; PLASMA ; AGE ; genetics ; FIBER ; MUSCLE ; PARAMETERS ; MORPHOLOGY ; SKELETAL-MUSCLE ; PREDICTION ; BODY ; POOR-PROGNOSIS ; heredity ; OXYGEN ; BIOPSY ; exercise ; MASSES ; BODIES ; REGRESSION ; INCREASE ; WEIGHT ; LIFE ; PHYSICAL-ACTIVITY ; HEIGHT ; QUALITY-OF-LIFE ; LEVEL ; MYOPATHY ; PLASMA-LEVELS ; technique ; USA ; LOSSES ; uptake ; correlation ; cachexia ; myopathies ; PREDICT ; BIOPSIES ; INCREASES ; - ; RESONANCE ; CANCER DIAGNOSIS ; TRACK ; FOXO TRANSCRIPTION FACTORS ; cancer cachexia ; muscle biopsy ; muscle morphology ; muscle wasting
    Abstract: Progressive muscle wasting is a central feature of cancer-related cachexia and has been recognized as a determinant of poor prognosis and quality of life. However, until now, no easily assessable clinical marker exists that allows to predict or to track muscle wasting. The present study evaluated the potential of myoglobin (MG) plasma levels to indicate wasting of large locomotor muscles and, moreover, to reflect the loss of MG-rich fiber types, which are most relevant for daily performance. In 17 cancer-cachectic patients (weight loss 22%) and 27 age- and gender-matched healthy controls, we determined plasma levels of MG and creatine kinase (CK), maximal quadriceps muscle cross-sectional area (CSA) by magnetic resonance imaging, muscle morphology and fiber composition in biopsies from the vastus lateralis muscle, body cell mass (BCM) by impedance technique as well as maximal oxygen uptake (VO(2)max). In cachectic patients, plasma MG, muscle CSA, BCM, and VO(2)max were 30-35% below control levels. MG showed a significant positive correlation to total muscle CSA (r=0.65, p 〈 0.001) and to the CSA fraction formed by type 1 and 2a fibers (r=0.80, p 〈 0.001). However, when adjusted for body height and age by multiple regression, MG yielded a largely improved prediction of total CSA (multiple r=0.83, p 〈 0.001) and of fiber type 1 and 2a CSA (multiple r=0.89, p 〈 0.001). The correlations between CK and these muscle parameters were weaker, and elevated CK values were observed in 20% of control subjects despite a prior abstinence from exercise for 5 days. In conclusion, plasma MG, when adjusted for anthropometric parameters unaffected by weight, may be considered as a novel marker of muscle mass (CSA) indicating best the mass of MG-rich type 1 and 2a fibers as well as VO(2)max as an important functional readout. CK plasma levels appear to be less reliable because prolonged increases are observed in even subclinical myopathies or after exercise. Notably, cancer-related muscle wasting was not associated with increases in plasma MG or CK in this study
    Type of Publication: Journal article published
    PubMed ID: 17605115
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  • 9
    Keywords: tumor ; BLOOD ; Germany ; PERFUSION ; FOLLOW-UP ; imaging ; VOLUME ; DISEASE ; NEW-YORK ; TISSUE ; TUMORS ; NUCLEAR-MEDICINE ; PATIENT ; BLOOD-FLOW ; prognosis ; blood flow ; FLOW ; HIGH-RESOLUTION MEASUREMENT ; MR ; MRI ; TRACER BOLUS PASSAGES ; spectroscopic imaging ; PROGRESSION ; MAGNETIC-RESONANCE SPECTROSCOPY ; chemotherapy ; REGION ; PARAMETERS ; PREDICTION ; magnetic resonance imaging (MRI) ; nuclear medicine ; ASTROCYTOMAS ; GLIOMAS ; radiology ; BRAIN-TUMORS ; GRADE ; TUMOR TISSUE ; analysis ; methods ; NUCLEAR ; fractionated stereotactic radiotherapy ; USA ; MRSI ; female ; Male ; EVALUATE ; CONTRAST-ENHANCED MR ; blood volume ; MEDICINE ; BLOOD-VOLUME MAPS ; DSC-MRI ; MR-perfusion ; perfusion imaging ; WHO grade II astrocytomas
    Abstract: Background. This study evaluates whether MR perfusion imaging and spectroscopic imaging (MRSI) can depict anaplastic areas in WHO grade II astrocytomas, whether these areas are co-localized, and whether the prognosis can be better predicted. Material and methods. Fifteen patients (nine female, six male, aged 42 +/- 14 years) with WHO grade II astrocytomas but without preceding radio- or chemotherapy were examined every 3 months with MR perfusion imaging and MRSI (mean follow-up 18 months). Using a region of interest analysis, the regional relative cerebral blood volume (rrCBV) and blood flow (rrCBF) were measured in tumor tissue. In the same areas, choline/creatine (Cho/Cr) and choline/N-acetyl-aspartate (Cho/NAA) ratios were quantified. Results. During follow-up, nine patients had stable disease. In six patients, the tumor showed progression and contrast-enhancement. The progressing tumors had already had higher perfusion (rrCBF 2.1 +/- 1.4; rrCBV 1.9 +/- 1.1) parameters than the stable astrocytomas (rrCBF 1.2 +/- 0.6, p=0.01; rrCBV 1.4 +/- 0.8, p=0.05) at first examination. However, the Cho/NAA and Cho/Cr ratios only tended to be higher than in stable astrocytomas (Cho/NAA 2.4 +/- 1.0 vs. 2.0 +/- 1.5, p=0.23; Cho/Cr 1.7 +/- 0.6 vs. 1.4 +/- 0.5, p=0.06). In all six progressing tumors, areas of maximum perfusion and maximum Cho/NAA and Cho/Cr ratio were co-localized. During follow-up, contrast-enhancement was observed in these areas. Conclusions. MR perfusion imaging can depict anaplastic areas in WHO grade II astrocytomas earlier than conventional MRI and thus enables a better prediction of prognosis
    Type of Publication: Journal article published
    PubMed ID: 16924439
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  • 10
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    Journal of Nuclear Medicine 49 (Suppl. 2), 43S-63S 
    Keywords: CANCER ; CANCER CELLS ; CELLS ; tumor ; CELL ; CLINICAL-TRIAL ; Germany ; THERAPY ; imaging ; METABOLISM ; NUCLEAR-MEDICINE ; radiation ; PATIENT ; ACTIVATION ; MECHANISM ; IMPACT ; mechanisms ; MRI ; MAGNETIC-RESONANCE-SPECTROSCOPY ; molecular imaging ; ACID ; TRIAL ; TRIALS ; CLINICAL-TRIALS ; CANCER-CELLS ; ONCOGENE ; POSITRON-EMISSION-TOMOGRAPHY ; GLUCOSE ; treatment planning ; PET ; nuclear medicine ; MANAGEMENT ; PROTON MR SPECTROSCOPY ; MAMMARY EPITHELIAL-CELLS ; radiology ; molecular ; review ; ADVANCED BREAST-CANCER ; THERAPIES ; monitoring ; ALPHA-METHYL TYROSINE ; MOLECULAR-MECHANISMS ; NUCLEAR ; HIGH-GRADE GLIOMAS ; technique ; optical imaging ; USA ; MEDICINE ; clinical trial ; FATTY-ACID SYNTHASE ; VA ; glucose metabolism ; amino acid metabolism ; CHOLINE KINASE-ALPHA ; lipid metabolism ; RECURRENT PROSTATE-CANCER
    Abstract: 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
    Type of Publication: Journal article published
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