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Breast tumours responding to chemotherapy exhibit decreased [(18)F]fluoro-2-deoxy-D-glucose ([(18)F]FDG) incorporation. Underlying mechanisms of these changes is poorly understood. Here, in MCF-7 cells, responding to chemotherapy drugs commonly utilised in the treatment of breast cancer, [(18)F]FDG incorporation and several pivotal factors associated with [(18)F]FDG incorporation investigated. Methods. IC50 and subclinical doxorubicin, docetaxel, and tamoxifen doses determined using MTT assay. [(18)F]FDG incorporation by cells treated with IC50 drug doses for 48 hours and 72 hours were determined and FDG dephosphorylation estimated by measuring loss of 18F from [(18)F]FDG-preincubated cells (pulse-chase). Glucose transport determined by measuring initial uptake rate of non-metabolised glucose analogue omethylglucose; hexokinase activity and ATP content measured in cell homogenates; Cell cycle distribution determined using flow cytometry of propidium iodide stained nuclei. Results. [(18)F]FDG incorporation and ATP content decreased in cells after 72 hours treatment with IC50 doses of tamoxifen, doxorubicin, and docetaxel compared with untreated controls. Decreased glucose transport and/or hexokinase activity accompanied decreased [(18)F]FDG incorporation by MCF-7 cells treated with tamoxifen or doxorubicin but not docetaxel. Conclusions. Tumour cell [(18)F]FDG incorporation along with ATP content decreased by treatment with tamoxifen, doxorubicin and docetaxel paralleling clinical observations for solid tumours. Effect of each treatment on glucose transport and hexokinase activity was chemotherapy-drug dependent.

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AIMS: The aim of this review is to consolidate our knowledge on an important and rapidly expanding area of expertise. Numerous methods for predicting response (in terms of pathological response and survival) to neoadjuvant therapy (chemotherapy/chemo-radiotherapy) in oesophageal and junctional cancers have been proposed. This review concerns itself only with the use of positron emission tomography for such a purpose. At present there are no standardised criteria amongst PET trials as to what determines a response according to PET, what is the optimal time to perform PET in relation to the timing of neoadjuvant therapy, and what is the ideal method of quantifying PET tracer uptake. METHODS: An electronic search was performed of PubMed, Ovid and Embase websites to identify studies, in the English language, using the search terms: PET; oesophageal; oesophago-gastric; survival; cancer; response; chemotherapy and chemo-radiotherapy. The reference lists were searched manually to identify further relevant studies. RESULTS: Twenty-two studies were identified, all using (18)FDG as the tracer, using PET to predict response in terms of pathological response and survival following neoadjuvant therapy (chemotherapy/chemo-radiotherapy). PET had a varying degree of success in predicting both pathological response and survival outcomes, with only one study using PET to influence management decisions. CONCLUSIONS: PET seems a promising technique, but large-scale conclusions are hindered by small study numbers, lack of criteria as to what constitutes a response and markedly differing PET imaging times. A large randomised trial concerning a homogeneous group of patients and tumours is required before PET might be used to influence management.

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BACKGROUND: The aim of the study was to investigate whether pre-therapy vascular delivery assessment [using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI)] can predict reduction in breast cancer metabolism [detected using 2-[(18)F] fluoro-2-deoxy-D-glucose positron emission tomography ((18)F(-)FDG-PET)] after a single cycle of chemotherapy. Reduction in (18)F-FDG PET metabolism has previously been shown to correlate with histological response to primary chemotherapy. PATIENTS AND METHODS: Seventeen patients with large or locally advanced invasive ductal carcinomas of the breast were imaged using DCE-MRI and (18)F-FDG-PET prior to therapy and 20 days after the first cycle of chemotherapy. MRI data were analysed using a multi-compartment model. PET data were analysed using standardised uptake value (SUV) analysis. RESULTS: A significant association (P <0.05) was observed between pre-therapy DCE-MRI vascular parameters and the reduction in PET metabolism resulting from administration of one cycle of chemotherapy. CONCLUSIONS: A relationship was demonstrated between pre-therapy DCE-MRI vascular parameters and the reduction in PET metabolism after a single cycle of chemotherapy. This suggests that reduction in PET metabolism as a result of chemotherapy may be dependent, at least in part, on pre-therapy vascular delivery. These pre-therapy vascular characteristics may be suitable for use as a surrogate measure for initial chemotherapy delivery, a key factor in chemotherapeutic efficacy.

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BACKGROUND: Hibernating myocardium is associated with increased cardiovascular events. Increased QT dispersion on the surface electrocardiogram is a marker for serious ventricular arrhythmias. In this study, we determine whether hibernating myocardium is associated with increased QT dispersion in patients with coronary artery disease and impaired left ventricular contraction. METHODS: Positron emission tomography with (13)N-ammonia and (18)F-fluorodeoxyglucose determined the presence of metabolic-perfusion mismatch defect. QT dispersion was measured by means of a digitizing tablet with validated software. QT intervals were measured on two separate occasions by two investigators blinded to the result of the positron emission tomography scans. RESULTS: Forty-two patients with impaired left ventricular contraction were studied. They were divided into two groups: group A was made up of patients with mismatch defects (n = 26) and group B was made up of patients with no mismatch defects (n = 16). The mean (SD) QT dispersion measurements were 61.7 +/- 29.8 ms and 70 +/- 24.6 ms for groups A and B, respectively (not significant). When the patients were divided according to the dominant viability status of the impaired myocardial segment, a similar result was found. The patients whose impaired myocardium was dominantly hibernating (n = 19) had a mean QT dispersion of 66.4 +/- 31.9 ms compared with 63.6 +/- 24.8 ms in the patients whose impaired myocardium was mainly scarred (not significant). CONCLUSIONS: QT dispersion is not affected by the presence of hibernating myocardium and is therefore not clinically useful in identifying patients with this phenomenon. This is in contrast with recent reports by other groups and calls for further investigation of this dichotomy.

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PURPOSE: To determine whether [(18)F]-fluorodeoxy-D-glucose ([(18)F]-FDG) positron emission tomography (PET) can predict the pathologic response of primary and metastatic breast cancer to chemotherapy. PATIENTS AND METHODS: Thirty patients with noninflammatory, large (> 3 cm), or locally advanced breast cancers received eight doses of primary chemotherapy. Dynamic PET imaging was performed immediately before the first, second, and fifth doses and after the last dose of treatment. Primary tumors and involved axillary lymph nodes were identified, and the [(18)F]-FDG uptake values were calculated (expressed as semiquantitative dose uptake ratio [DUR] and influx constant [K]). Pathologic response was determined after chemotherapy by evaluation of surgical resection specimens. RESULTS: Thirty-one primary breast lesions were identified. The mean pretreatment DUR values of the eight lesions that achieved a complete microscopic pathologic response were significantly (P =.037) higher than those from less responsive lesions. The mean reduction in DUR after the first pulse of chemotherapy was significantly greater in lesions that achieved a partial (P =.013), complete macroscopic (P =.003), or complete microscopic (P =.001) pathologic response. PET after a single pulse of chemotherapy was able to predict complete pathologic response with a sensitivity of 90% and a specificity of 74%. Eleven patients had pathologic evidence of lymph node metastases. Mean pretreatment DUR values in the metastatic lesions that responded did not differ significantly from those that failed to respond (P =.076). However, mean pretreatment K values were significantly higher in ultimately responsive cancers (P =.037). The mean change in DUR and K after the first pulse of chemotherapy was significantly greater in responding lesions (DUR, P =.038; K, P =.012). CONCLUSION: [(18)F]-FDG PET imaging of primary and metastatic breast cancer after a single pulse of chemotherapy may be of value in the prediction of pathologic treatment response.

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OBJECTIVE: To investigate whether QRS morphology on the surface ECG can be used to predict myocardial viability. DESIGN: ECGs of 58 patients with left ventricular impairment undergoing positron emission tomography (PET) were studied. (13)N-Ammonia (NH(3)) and (18)F-fluorodeoxyglucose (FDG) were the perfusion and the metabolic markers, respectively. The myocardium is scarred when the uptake of both markers is reduced (matched defect). Reduced NH(3) uptake with persistent FDG uptake (mismatched defect) represents hibernating myocardium. First, the relation between pathological Q waves and myocardial scarring was investigated. Second, the significance of QR and QS complexes in predicting hibernating myocardium was determined. RESULTS: As a marker of matched PET defects, Q waves were specific (79%) but not sensitive (41%), with a 77% positive predictive accuracy and a poor (43%) negative predictive accuracy. The mean size of the matched PET defect associated with Q waves was 20% of the left ventricle. This was not significantly different from the size of the matched PET defects associated with no Q waves (18%). Among the regions associated with Q waves on the ECG, there were 16 regions with QR pattern (group A) and 23 regions with QS pattern (group B). The incidence of mismatched PET defects was 19% of group A and 30% of group B (NS). CONCLUSIONS: Q waves are specific but not sensitive markers of matched defects representing scarred myocardium. Q waves followed by R waves are not more likely to be associated with hibernating myocardium than QS complexes.

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Breast cancer is the commonest malignancy to affect women. The malignant process may present clinicians with problems in establishing the diagnosis expeditiously, accurately staging the disease and assessing tumour response to primary systemic chemotherapy. Considerable recent interest has focused on the application of imaging techniques that utilize tumour-specific gamma-ray-emitting radiopharmaceuticals to resolve these problems. The wide availability of gamma camera systems makes single photon-imaging techniques, using radiopharmaceuticals incorporating conventional isotopes, attractive options. However, results concerning the detection of the primary breast cancer and the staging of axillary lymph nodes suggest that these techniques would appear to offer no significant advantages, when compared with those obtained using standard diagnostic methods. Dual gamma-ray-emission imaging by positron emission tomography (PET) may offer an alternative solution. Studies performed show that PET can accurately detect primary breast cancers, stage locoregional lymph nodes and visualize distant tumour metastases. Furthermore, PET may be able to monitor early tumour response to chemotherapy agents. It would appear, therefore, that dual gamma emission might have an important role to play in the management of patients with breast cancer.

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