The value of 18F-fluorodeoxyglucose PET (18F-FDG PET) and MRI spectroscopy in underpinning suspicious breast cancer

The aim of this study was to evaluate the value of MRI spectroscopy and association with the altered glucose metabolism on 18-FDG PET/CT in patients with suspicious breast cancer. Eight selected breast cancer patients with BIRADS 4 or 5 on mammogram were recruited and patients underwent 18F-FDG PET/CT MRI (spectroscopy). The standardise uptake value (SUVmax) was analysed to determine the degree of the altered glucose metabolism on the PET. The metabolites of tumor lesions were measured using in vivo proton MR spectroscopy (MRS) of the breast. There were eight females with a mean age of 55.3±12.2 years with a biopsy result of invasive ductal carcinoma (2), lobular carcinoma (1) and benign lesion (5). There was a significant difference between the mean of the malignant tumour (SUVmax 4.28±3.74 g/ml) and the mean of the benign tumour (SUVmax: 2.33±0.9 g/ml). On the per-lesional basis of the MRS correlate with SUVmax, the suspicious breast tissue exhibited raised creatinine metabolites (mean: 3.39±0.54u) with significant correlation SUVmax mean 3.06±2.34 as compared to N-acetyl Aspartate (NAA), (mean: 2.84±0.99u) and choline (mean: 2.46± 0.70 u). This study showed that high SUVmax was associated with malignant cancer and the high creatinine metabolite that correlated with the SUVmax could potentially be utilised as a surrogate marker in detecting breast cancer

HIF-1 ACTIVATION AND INFLAMMATORY RESPONSES TO HYPOXIA

Acute hypoxia is a significant physiological danger during high-altitude flying and military aircraft missions. The human brain requires a constant supply of oxygen to function properly, and is susceptible to settings with low availability of air oxygen. Hypoxia can influence inflammatory signalling, and both central and systemic responses can activate HIF pathway genes. HIFs are critical molecules that regulate inflammation andhypoxia, ensuring appropriate cell function and survival. Hypoxia is the condition in which insufficient oxygen reaches the body\u27s tissues. It can be caused by a decrease in partial oxygen pressure (PO2) in the environment, problems with breathing and/or oxygen transport, or the inability of tissues to utilise oxygen. Different organs are hypoxic due to differences in tissue oxygen tensions, which are determined by differences in aerobic metabolism. Extremely hypoxic individuals have the most dramatic systemic and neurological adaptations to persistent hypoxia. In this review, we provide an overview of central and systemic responses to hypoxia and discuss the activation of HIF-1 pathway

Breast cancer aggressiveness, miRNA and choline

The level of choline kinase in human breast cancer cells was found to be overexpress as compared to normal human mammary epithelial cells. This book presents a study that we investigated the potential expression of choline in 18F-FCH PET/CT as compared to F18Fluorodeoxyglucose PET/CT and correlations with expression of miRNA, CD47 and histo-immunochemical markers of estrogen, progesterone and HER2 in detecting aggressiveness of breast cancer.Twenty one patients with Birads 4 or 5 on mammogram and recurrent breast carcinoma underwent imaging of 18F-Fluorocholine and 18F-Fluorodeoxyglucose PET/CT. Tissue biopsy and histo-immunochemical results with blood sampling of expression of miRNA-21,miRNA-155 and CD47 were recorded. The data were evaluated by experienced nuclear imaging using the biopsy and histo-immunochemical findings as a gold standard. There were 21 females with a mean age of 52.82 ± 10.71 years. There is a significant evidence of high uptake of 18F-Fluorocholine PET/CT in the metastatic lesions (2.27±3.19) as compare to 18F-Fluorodeoxyglucose (1.74±2.32, p=0.004). While there is a significant association between high 18F-Fluorocholine uptake (3.53±3.51,p=0.005) with HER2-ve (1.98±2.14, p=0.009) in metastatic lesions and lymph node. High uptake of 18F-Fluorocholine showed a significant correlation with expression of miRNA-21 in lymph node (1.81±2.21,p=0.05) and metastasis lesions (3.33±3.61,p=0.02). There is also a significant correlation between high choline uptake with expression of miRNA-155 (1.47±1.99,p=0.01) and CD47 (0.85±0.23,p=0.008) in lymph node and 18F-Fluorocholine showed high sensitivity and specificity (40%,68.8%) compared to 18F-Fluorodeoxyglucose (27.3%,60%). There is a significant association miRNA-155 between patients with recurrent breast cancer and non-recurrent breast cancer (p=0.026) and expression of HER2 –ve (p=0.042).We concluded that higher choline uptake in 18F-Fluorocholine would potentially be used as novel surrogate marker for detection and prediction of an aggressive breast cancer with strong correlation with the protein overexpression of miRNA-155, miRNA-21,CD47 and HER2-ve

PET-MRI imaging of cellular trafficking of lipid metabolism and its association with inflammatory and genetic markers in breast cancer

The tumour landscapes are varied, and depending on the orchestration of specific molecular pathways, signaling of its early manifestation could be understood. The conventional ways to signal the metabolic expression of cancers are notably via recognizing the altered glycolytic pathways in the cells whereby the transport of glucose is unchecked by the high demand of the ATP production by the cancer cells. It is notwithstanding that by relying on the glucose analogue (flurodeoxyglucose, FDG) signaling in cells, there are other cellular mechanism deemed to be explored, that is, the cell membrane or lipid metabolism. Molecular imaging–based nanoparticles are proving useful for cell trafficking studies, whereas radionuclide- and optical-based molecular–genetic reporters are yet to be determined. On the other hand, for receptor- or enzyme-based imaging or for studying the pharmacokinetic disposition of chemotherapeutic agents, the radionuclide-based techniques predominate. This review highlights the utility of the molecular imaging techniques in expressing the altered lipid metabolism, that is, choline transport in cells as an index of tumour aggressiveness in breast cancer

The association of FDG-PET (SUVmax) and inflammatory marker in predicting tumour aggressiveness

Chronic inflammation is associated with processes that contribute to the onset or progression of cancer. This study examined the correlation between dichotomised patients with malignant tumours and inflammatory markers based on the altered glucose metabolism measured by the FDG SUVmax that underpins the degree of tumour aggressiveness. Thirty-one patients underwent 18F-FDG PET/CT for various carcinoma along with blood inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL6), lipid profile and fasting blood glucose (FBG) levels were obtained in retrospective study. Patients were dichotomised by the cut-off SUVmax value of 6.0 dl/ml derived from curve analysis (P=-0.025). The mean age of the subjects were 53.16 ± 12.06 years and mean SUVmax of 8.80±6.27 g/ml. Significant correlation was noted between the SUVmax and CRP and IL6 (r=0.361; P 6.0 dl/ml was inversely related to IL-6 (OR: 0.049, with p<0.005). Serum inflammatory markers and endogenous glucose are associated with a potentially more aggressive malignant cancer. In particular, IL6 may be used as a useful surrogate marker for tumour aggressiveness with an important prognostic value

Vulnerable plaque detection: The role of 18-fluorine fluorodeoxyglucose in identifying high risk patients

Positron emission tomography computed tomography (PET-CT) is a combined functional and structural multi modality imaging tool that can be utilized to detect vulnerable and atherosclerotic plaques. In this study we observe the prevalence of active and calcified plaques in selected arteries during whole-body 18F-FDG PET-CT and correlate the findings with risk factors in developing coronary artery disease. There was a significant relationship between patients with high body mass index and vulnerable plaques. We concluded that 18F-FDG PET-CT can be utilized in detecting focal high FDG uptake within vascular plaque in early recognition of high risk patients having vascular accidents

Choline as a molecular imaging biomarker for assessing breast cancer aggressiveness

The level of choline kinase in human breast cancer cells was found to be overexpress as compared to normal human mammary epithelial cells. In this study we investigated the potential expression of choline in 18F-FCH PET/CT as compared to F18Fluorodeoxyglucose PET/CT and correlations with expression of miRNA, CD47 and histo-immunochemical markers of estrogen, progesterone and HER2 in detecting aggressiveness of breast cancer. Twenty one patients with Birads 4 or 5 on mammogram and recurrent breast carcinoma underwent imaging of 18F-Fluorocholine and 18F-Fluorodeoxyglucose PET/CT. Tissue biopsy and histo-immunochemical results with blood sampling of expression of miRNA-21,miRNA-155 and CD47 were recorded. The data were evaluated by experienced nuclear imaging using the biopsy and histo-immunochemical findings as a gold standard. There were 21 females with a mean age of 52.82 ± 10.71 years. There is a significant evidence of high uptake of 18F-Fluorocholine PET/CT in the metastatic lesions (2.27±3.19) as compare to 18F-Fluorodeoxyglucose (1.74±2.32, p=0.004).While there is a significant association between high 18F-Fluorocholine uptake (3.53±3.51,p=0.005) with HER2-ve (1.98±2.14, p=0.009) in metastatic lesions and lymph node. High uptake of 18F-Fluorocholine showed a significant correlation with expression of miRNA-21 in lymph node (1.81±2.21,p=0.05) and metastasis lesions (3.33±3.61,p=0.02). There is also a significant correlation between high choline uptake with expression of miRNA-155 (1.47±1.99,p=0.01) and CD47 (0.85±0.23,p=0.008) in lymph node and 18F-Fluorocholine showed high sensitivity and specificity (40%,68.8%) compared to 18F-Fluorodeoxyglucose (27.3%,60%). There is a significant association miRNA-155 between patients with recurrent breast cancer and non recurrent breast cancer (p=0.026) and expression of HER2 –ve (p=0.042). We concluded that higher choline uptake in 18F-Fluorocholine would potentially be used as novel surrogate marker for detection and prediction of an aggressive breast cancer with strong correlation with the protein overexpression of miRNA-155, miRNA-21,CD47 and HER2-ve

Role of 18fluorine fluorodeoxyglucose in vulnerable plaque detection for identifying high risk patients

FDG-PET/CT is a combined functional and structural multi modality imaging tool that can be utilized to detect atherosclerotic plaques. This study observed the prevalence of active and calcified plaques in selected arteries during whole-body 18F-FDG PET-CT and correlate the findings with risk factors in coronary artery disease. Beside that, the relationship of active and calcified plaque activity with inflammatory biomarker were determine from the blood marker. The record of 47 patients, which were divided into 17 patients retrospectively and 30 patient prospectively alongside serum inflammatory marker (eg.IL-6 and CRP) and cholesterol (eg lipid profile) undergone whole body FDG PET-CT study in various oncology cases were reviewed. To evaluate the cutoff value for abnormal uptake, retrospective study was conducted to identify patient at risk of developing vascular disease. Mean age was 58±10.3 years old. The presence of 18F-FDG uptake and calcification in selected vascular walls were evaluated. The composition of plaque were recorded using CT value in Housfield unit (HU max). The intensity of 18F-FDG uptake was measured as maximum blood-normalized standardize uptake value (SUVmax). 18F-FDG uptake (SUVmax) and calcification (HUmax) was significantly highest in the carotid walls with (1.91±0.11) and (631.7±215.5) respectively. There was significant relationship between high BMI (overweight) with 18FDG uptake, while calcified artery significant related with hyperlipidemia, diabetes mellitus and hypertension. However the blood marker (such as C-reactive protein) showed significant with high 18FDG uptake and high calcified artery. Beside that, calcified artery showed there was no significant and direct correlation with inflamed vascular wall (SUVmax). This study showed that 18F-FDG PET-CT can be utilized in detecting focal high FDG uptake within vascular plaque in early recognition of high risk patients having coronary artery disease