High fluoro-D-glucose Uptake Research Articles

Metabolic factors associated with the prognosis of oligometastatic patients treated with stereotactic body radiotherapy.

Over the past two decades, it has been established that cancer patients with oligometastases, i.e., only a few detectable metastases confined to one or a few organs, may benefit from an aggressive local treatment approach such as the application of high-precision stereotacticbody radiotherapy (SBRT). Specifically, some studies have indicated that achieving long-term local tumor control of oligometastases is associated with prolonged overall survival. This motivates investigations into which factors may modify the dose-response relationship of SBRT by making metastases more or less radioresistant. One such factor relates to the uptake of the positron emission tomography tracer 2-deoxy-2-[18F]fluoro-D-glucose (FDG) which reflects the extent of tumor cell glycolysis or the Warburg effect, respectively. Here we review the biological mechanisms how the Warburg effect drives tumor cell radioresistance and metastasis and draw connections to clinical studies reporting associations between high FDG uptake and worse clinical outcomes after SBRT for oligometastases. We further review the evidence for distinct metabolic phenotypes of metastases preferentially seeding to specific organs and their possible translation into distinct radioresistance. Finally, evidence that obesity and hyperglycemia also affect outcomes after SBRT will be presented. While delivered dose is the main determinant of a high local tumor control probability, there might be clinical scenarios when metabolic targeting could make the difference between achieving local control or not, for example when doses have to be compromised in order to spare neighboring high-risk organs, or when tumors are expected to be highly therapy-resistant due to heavy pretreatment such as chemotherapy and/or radiotherapy.

Serum glucose excretion after Roux-en-Y gastric bypass: a potential target for diabetes treatment

ObjectiveThe mechanisms underlying type 2 diabetes resolution after Roux-en-Y gastric bypass (RYGB) are unclear. We suspected that glucose excretion may occur in the small bowel based on observations in humans....

Clinical implications of increased uptake in bone marrow and spleen on FDG-PET in patients with bacteremia

PurposeTo investigate which clinical factors and laboratory values are associated with high FDG uptake in the bone marrow and spleen on 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) in patients with bacteremia.MethodsOne hundred forty-five consecutive retrospective patients with bacteremia who underwent FDG-PET/CT between 2010 and 2017 were included. Mean standard uptake values (SUVmean) of FDG in bone marrow, liver, and spleen were measured. Bone marrow-to-liver SUV ratios (BLR) and spleen-to-liver SUV ratios (SLR) were calculated. Linear regression analyses were performed to examine the association of BLR and SLR with age, gender, hemoglobin, leukocyte count, platelets, glucose level, C-reactive protein (CRP), microorganism, days of antibiotic treatment before FDG-PET/CT, infection focus, use of immunosuppressive drugs, duration of hospital stay (after FDG-PET/CT), ICU admission, and mortality.ResultsC-reactive protein (p = 0.006), a cardiovascular or musculoskeletal focus of infection (p = 0.000 for both), and bacteremia caused by Gram-negative bacteria (p = 0.002) were independently and positively associated with BLR, while age (p = 0.000) and glucose level before FDG-PET/CT (p = 0.004) were independently and negatively associated with BLR.For SLR, CRP (p = 0.001) and a cardiovascular focus of infection (p = 0.020) were independently and positively associated with SLR, while age (p = 0.002) and glucose level before FDG-PET/CT (p = 0.016) were independently and negatively associated with SLR.ConclusionHigh FDG uptake in the bone marrow is associated with a higher inflammatory response and younger age in patients with bacteremia. In patients with high FDG uptake in the bone marrow, a cardiovascular or musculoskeletal focus of infection is more likely than other foci, and the infection is more often caused by Gram-negative species. High splenic FDG uptake is associated with a higher inflammatory response as well, and a cardiovascular focus of infection is also more likely in case of high splenic FDG uptake.

Indeterminate Findings on Oncologic PET/CT: What Difference Does PET/MRI Make?

Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) has become the standard of care for the initial staging and subsequent treatment response assessment of many different malignancies. Despite this success, PET/CT is often supplemented by MRI to improve assessment of local tumor invasion and to facilitate detection of lesions in organs with high background FDG uptake. Consequently, PET/MRI has the potential to expand the clinical value of PET examinations by increasing reader certainty and reducing the need for subsequent imaging. This study evaluates the ability of FDG-PET/MRI to clarify findings initially deemed indeterminate on clinical FDG-PET/CT studies. A total of 190 oncology patients underwent whole-body PET/CT, immediately followed by PET/MRI utilizing the same FDG administration. Each PET/CT was interpreted by our institution's nuclear medicine service as a standard-of-care clinical examination. Review of these PET/CT reports identified 31 patients (16%) with indeterminate findings. Two readers evaluated all 31 PET/CT studies, followed by the corresponding PET/MRI studies. A consensus was reached for each case, and changes in interpretation directly resulting from PET/MRI review were recorded. Interpretations were then correlated with follow-up imaging, pathology results, and other diagnostic studies. In 18 of 31 cases with indeterminate findings on PET/CT, PET/MRI resulted in a more definitive interpretation by facilitating the differentiation of infection/inflammation from malignancy (15/18), the accurate localization of FDG-avid lesions (2/18), and the characterization of incidental non-FDG-avid solid organ lesions (1/18). Explanations for improved reader certainty with PET/MRI included the superior soft tissue contrast of MRI and the ability to assess cellular density with diffusion-weighted imaging. The majority (12/18) of such cases had an appropriate standard of reference; in all 12 cases, the definitive PET/MRI interpretation proved correct. These 12 patients underwent six additional diagnostic studies to clarify the initial indeterminate PET/CT findings. In the remaining 13 of 31 cases with indeterminate findings on both PET/CT and PET/MRI, common reasons for uncertainty included the inability to distinguish reactive from malignant lymphadenopathy (4/13) and local recurrence from treatment effect (2/13). Indeterminate PET/CT findings can result in equivocal reads and additional diagnostic studies. PET/MRI may reduce the rate of indeterminate findings by facilitating better tumor staging, FDG activity localization, and lesion characterization. In our study, PET/MRI resulted in more definitive imaging interpretations with high accuracy. PET/MRI also showed potential in reducing the number of additional diagnostic studies prompted by PET/CT findings. Our results suggest that whole-body PET/MRI provides certain diagnostic advantages over PET/CT, promotes more definitive imaging interpretations, and may improve the overall clinical utility of PET.

High FDG uptake areas on pre-radiotherapy PET/CT identify preferential sites of local relapse after chemoradiotherapy for locally advanced oesophageal cancer.

The high failure rates in the radiotherapy (RT) target volume suggest that patients with locally advanced oesophageal cancer (LAOC) would benefit from increased total RT doses. High 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) uptake (hotspot) on pre-RT FDG positron emission tomography (PET)/CT has been reported to identify intra-tumour sites at increased risk of relapse after RT in non-small cell lung cancer and in rectal cancer. Our aim was to confirm these observations in patients with LAOC and to determine the optimal maximum standardized uptake value (SUVmax) threshold to delineate smaller RT target volumes that would facilitate RT dose escalation without impaired tolerance. The study included 98 consecutive patients with LAOC treated by chemoradiotherapy (CRT). All patients underwent FDG PET/CT at initial staging and during systematic follow-up in a single institution. FDG PET/CT acquisitions were coregistered on the initial CT scan. Various subvolumes within the initial tumour (30, 40, 50, 60, 70, 80 and 90% SUVmax thresholds) and in the subsequent local recurrence (LR, 40 and 90% SUVmax thresholds) were pasted on the initial CT scan and compared[Dice, Jaccard, overlap fraction (OF), common volume/baseline volume, common volume/recurrent volume]. Thirty-five patients had LR. The initial metabolic tumour volume was significantly higher in LR tumours than in the locally controlled tumours (mean 25.4 vs 14.2 cc; p = 0.002). The subvolumes delineated on initial PET/CT with a 30-60% SUVmax threshold were in good agreement with the recurrent volume at 40% SUVmax (OF = 0.60-0.80). The subvolumes delineated on initial PET/CT with a 30-60% SUVmax threshold were in good to excellent agreement with the core volume (90% SUVmax) of the relapse (common volume/recurrent volume and OF indices 0.61-0.89). High FDG uptake on pretreatment PET/CT identifies tumour subvolumes that are at greater risk of recurrence after CRT in patients with LAOC. We propose a 60% SUVmax threshold to delineate high FDG uptake areas on initial PET/CT as reduced target volumes for RT dose escalation.

Positron Emission Tomography with [18F]-3′-Deoxy-3′fluorothymidine (FLT) as a Predictor of Outcome in Patients with Locally Advanced Resectable Rectal Cancer: a Pilot Study

This pilot study was performed to evaluate whether tumor uptake of (18)F-labeled 3'-deoxy-3'fluorothymidine (FLT), a proliferative radiotracer, at baseline and early during therapy, is predictive of outcome in locally advanced rectal cancer. Fourteen patients underwent positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and FLT before therapy and PET with FLT approximately 2weeks after initiating neoadjuvant chemoradiotherapy. FLT and FDG uptake were evaluated qualitatively and by maximum standardized uptake value (SUV(max)). Tumor FLT and FDG uptake were correlated with disease-free survival (DFS). Thirteen patients underwent surgery after therapy, one died before surgery with progressive disease. FDG-PET/computed tomography detected regional lymph node metastases in five and FLT-PET was positive in one. High pretherapy FDG uptake (SUV(max) ≥ 14.3), low during-therapy FLT uptake (SUV(max) < 2.2), and high percentage change in FLT uptake (≥60%) were predictive of improved DFS (p < 0.05 for all three values). Pretherapy FDG uptake, during-therapy FLT uptake, and percentage change in FLT uptake were equally predictive of DFS.

Characterization of a novel rat cholangiocarcinoma cell culture model-CGCCA

To characterize a culture model of rat CCA cells, which were derived from a transplantable TTA-induced CCA and designated as Chang Gung CCA (CGCCA). The CGCCA cells were cultured at in vitro passage 12 times on a culture dish in DMEM medium. To measure the doubling time, 10(3) cells were plated in a 96-well plate containing the growth medium. The cells were harvested 4 to 10 d after seeding, and a standard MTT assay was used to measure the growth. The phenotype of CACCA cell and xenograft was determined by immunohistochemical study. We also determine the chromosomal alterations of CGCCA, G-banding and spectral karyotyping studies were performed. The CGCCA cell line was transplanted into the nude mice for examining its tumorigenicity. 2-Deoxy-2-((18)F)fluoro-D-glucose (FDG) autoradiography was also performed to evaluate the FDG uptake of the tumor xenograft. The doubling time for the CGCCA cell line was 32 h. After transplantation into nude mice, FDG autoradiography showed that the tumors formed at the cell transplantation site had a latency period of 4-6 wk with high FDG uptake excluding necrosis tissue. Moreover, immunohistochemical staining revealed prominent cytoplasmic expression of c-erb-B2, CK19, c-Met, COX-II, EGFR, MUC4, and a negative expression of K-ras. All data confirmed the phenotypic features of the CGCCA cell line coincide with the xenograft mice tumors, indicating cells containing the tumorigenicity of CCA originated from CCA. In addition, karyotypic banding analysis showed that the diploid (2n) cell status combines with ring and giant rod marker chromosomes in these clones; either both types simultaneously appeared or only one type of marker chromosome in a pair appeared in a cell. The major materials contained in the marker chromosome were primarily identified from chromosome 4. The current CGCCA cell line may be used as a non-K-ras effect CCA model and to obtain information and reveal novel pathways for CCA. Further applications regarding tumor markers or therapeutic targeting of CCA should be addressed accordingly.

PET-CT Evaluation of 2-Deoxy-2-[ 18F]Fluoro-D-Glucose Myocardial Uptake: Effect of Respiratory Motion

PURPOSE: Using combined positron emission tomography (PET) and computerized tomography (CT) instrumentation, PET measurements of myocardial tracer uptake performed with CT attenuation correction may differ from estimates using 68Germanium transmission correction due to differences in respiratory motion during acquisition. The purpose of this study is to evaluate the effects of respiratory motion on the CT acquisition and emission corrected images, and to evaluate the correlation of diaphragm position with regional differences in myocardial 2-deoxy-2-[ 18F]fluoro-D-glucose (FDG) uptake in clinical studies. METHODS: A canine myocardial FDG-PET study was performed with controlled ventilation. Attenuation correction was performed with CT scans acquired at end expiration and end inspiration, and throughout multiple respiratory cycles with conventional 68Germanium transmission scan. The mean myocardial FDG activity was evaluated in multiple short axis regions of interest (n = 40) using each of these three AC maps. Differences in emission during CT acquisitions were identified and expressed as bias (%) compared to 68Germanium corrected data. Ten patient studies with high myocardial FDG uptake were retrospectively selected from a clinical population referred for whole body oncology studies. All subjects had both CT and 68Germanium AC. After analysis for diaphragm misregistration defined by imaging and diaphragm position, subjects were divided into two groups: Group A controls (n = 5) with no or mild misregistration, and Group B (n = 5) with moderate or severe diaphragm misregistration. Regional emission bias (n = 400 regions) from CT correction was defined by using the 68Germanium attenuation corrected emission as the standard. RESULTS: The canine study using end-expiration CT for attenuation correction showed regional overestimation of activity (1.8%±0.7% for inferior; 2.0%±0.5% for inferolateral) compared to the 68Germanium corrected images. Conversely, the study using end-inspiration CT attenuation correction showed underestimation (−3.9%±0.5% for inferior; −4.0%±0.6% for inferolateral) of myocardial activity compared to 68Germanium corrected images. In subjects, Group B showed significant relative underestimation of FDG myocardial activity compared to Group A in the regions adjacent to the diaphragm including the inferior ( P = 0.0003), inferoseptal ( P = 0.008), and inferolateral ( P<0.0001) regions. CONCLUSIONS: In canine myocardium, differences in respiration influenced CT attenuation maps and subsequent CT attenuation corrected PET images in the inferolateral and lateral regions. In clinical PET-CT studies, diaphragm misregistration is associated with relative decreased emission activity in inferior, inferoseptal, and inferolateral walls. Nonuniformity of bias in the emission data can affect quantitative accuracy, and therefore, the interpretation of myocardial viability. Further studies are required to determine if the frequency of these findings warrants the use of 68Germanium transmission attenuation correction in myocardial FDG-PET. The quantitative differences between these techniques were typically modest.

Contribution of PET in the detection of liver metastases from pancreatic tumours

AIM: Although uptake of 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) in the liver is basically high, metastatic liver tumours are known to be positive on positron emission tomography (PET). The purpose of this study is to evaluate the diagnostic accuracy of FDG-PET in detecting hepatic metastases from pancreatic cancer. METHODS: Thirty-four patients with histologically proven malignant tumours of the pancreas underwent FDG-PET, computed tomography (CT) and transabdominal ultrasound (US). The findings of PET, CT and US were compared with the histopathologic findings at surgery or with clinical follow-up and the diagnostic accuracy of PET was evaluated. RESULTS: PET showed 28 regions of high FDG uptake (SUV = 3.3−9.1) in 13 patients. Twenty-six foci were metastatic lesions confirmed by surgery ( n = 11), clinical follow-up ( n = 10) or autopsy ( n = 5). FDG-PET accurately differentiated seven metastatic lesions from cysts when the diagnosis by US or CT was unreliable because of the small size of the lesion. In two patients who had areas of high uptake in the liver, no metastases were detected by surgery. FDG-PET showed no areas of increased uptake in 21 patients. Surgery revealed no metastatic lesions in the liver in 20 of 21 patients, but a liver metastasis was found at surgery in one patient. The diagnostic accuracy of FDG-PET was 90%, which was comparable with that of US or CT. CONCLUSION: Our data suggest that PET is reliable in detecting liver, metastases from pancreatic cancer.

PET imaging of primary mediastinal tumours

Mediastinal masses include a wide variety of tumours and remain an interesting diagnostic challenge for radiologist. We performed positron emission tomography (PET) studies of primary mediastinal tumours in order to predict the malignancy of these tumours preoperatively. Twenty-two patients with primary mediastinal tumours were studied with PET using 2-deoxy-2-[18F]fluoro-D-glucose (FDG). The histological findings of surgical pathology or biopsy, or mediastinoscopy were compared with those of computerised tomography (CT) and PET. PET images were evaluated semiquantitatively using the differential uptake ratio (DUR). Increased FDG uptake was observed in nine of ten patients with malignant tumours, including thymic carcinomas, lymphomas, invasive thymomas and a case of sarcoidosis. A moderate level of FDG uptake was found in a myeloma, non-invasive thymomas, and a schwannoma, whereas a low uptake was observed in a teratoma and various benign cysts. The mean FDG uptake of malignant tumours was significantly higher than that of benign tumours. Both thymic cancer and invasive thymoma showed a high FDG uptake. CT examination resulted in three false-negative and two false-positive cases when used in predicting tumour invasion, while PET was associated with a false-positive and a false-negative case. In conclusion, the use of FDG with PET is clinically helpful in evaluating the malignant nature of primary mediastinal tumours. Our results also suggest that a high FDG uptake reflects the invasiveness of malignant nature of thymic tumours.