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2-Deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) accumulation in inflammatory lesions can confound the diagnosis of cancer. In this study, we investigated [18F]FDG accumulation and efflux in relation to the genes and proteins involved in glucose metabolism in murine inflammation and cancer models. [18F]FDG accumulation and [18F]FDG efflux were measured in cancer cells (breast cancer, glioma, thyroid cancer, and hepatoma cells) and RAW 264.7 cells (macrophages) activated with lipopolysaccharide (LPS). The levels of mRNA expression were measured by real-time quantitative PCR (qPCR). The expression of glucose metabolism–related proteins was detected by western blotting. Dynamic [18F]FDG positron emission tomography-computed tomography (PET/CT) images were acquired for 2 h in tumor-bearing BALB/c nude mice and inflammatory mice induced by turpentine oil. [18F]FDG accumulation in MDA-MB-231 (breast cancer) increased with time, but that of HepG2 (hepatoma) reached a constant level after 120 min. [18F]FDG efflux in HepG2 was faster than that in MDA-MB-231. HepG2 strongly expressed glucose-6-phosphatase (G6Pase) compared with MDA-MB-231. [18F]FDG accumulation increased with time, and [18F]FDG efflux accelerated after the activation of RAW 264.7 cells. The expression levels of G6Pase, glucose transporter1 and glucose transporter3 (GLUT1 and GLUT3), and hexokinase II (HK II) increased after the activation of RAW 264.7 cells. [18F]FDG efflux in activated macrophages was faster than that in MDA-MB-231 cancer cells. MDA-MB-231 strongly expressed HK II protein compared with the activated RAW 264.7. In murine models, [18F]FDG accumulation in MDA-MB-231 cancer and inflammatory lesions increased with time, but that in HepG2 tumor increased until 20–30 min (SUVmeans ± SD (tumor/muscle), 3.0 ± 1.3) and then decreased (2.1 ± 0.9 at 110–120 min). There was no difference in the pattern of [18F]FDG accumulation with time in MDA-MB-231 tumors and inflammatory lesions. We found that [18F]FDG efflux accelerated in activated macrophages reflecting increased G6Pase expression after activation and lower expression of HK II protein than that in MDA-MB-231 cancer cells.

Evolving scientific evidence has begun to point towards hyperphosphorylated tau as a major neurotoxic component in the pathophysiological development of many major neurodegenerative conditions. In response to a need for accurate and reliable diagnosis and disease monitoring in clinical and trial settings, there has been great effort put into the development of tau radiotracers. While first-generation and second-generation radiotracers have provided a basis for assessing tau, concerns of inadequate specificity and selectivity have continued to motivate further study of these radiotracers and the development of novel radiopharmaceuticals. Given the prospective scientific and clinical value of a valid tau radiotracer, the molecular neuroimaging community must be aware of the most recent developments in the realm of tau radiotracer development. This brief review article will critically overview the most established tau radiotracers and, most importantly, concentrate on the progress of more recently developed tau radiotracers.

The applications of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/X-ray computed tomography (PET/CT) in the management of patients with breast cancer have been extensively studied. According to these studies, PET/CT is not routinely performed for the diagnosis of primary breast cancer, although PET/CT in specific subtypes of breast cancer correlates with histopathologic features of the primary tumor. PET/CT can detect metastases to mediastinal, axial, and internal mammary nodes, but it cannot replace the sentinel node biopsy. In detection of distant metastases, this imaging tool may have a better accuracy in detecting lytic bone metastases compared to bone scintigraphy. Thus, PET/CT is recommended when advanced-stage disease is suspected, and conventional modalities are inconclusive. Also, PET/CT has a high sensitivity and specificity to detect loco-regional recurrence and is recommended in asymptomatic patients with rising tumor markers. Numerous studies support the future role of PET/CT in prediction of response to neoadjuvant chemotherapy (NAC). PET/CT has a higher diagnostic value for prognostic risk stratification in comparison with conventional modalities. With the continuing research on the treatment planning and evaluation of patients with breast cancer, the role of PET/CT can be further extended.

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Purpose: Malignant cells exhibit increased rates of aerobic glycolysis. Here, we tested whether the accumulation of fluoro-deoxyglucose-6-phosphate (FDG6P) in ovarian cancers of differential malignancy reflects inversely correlated elevations of hexokinase (HK) and glucose-6-phosphatase (G6Pase) activities. Procedures: Twenty-nine women with suspected ovarian cancer had positron emission tomography (PET) prior to surgery. From fresh-frozen tissue, we determined the activities of HK and G6Pase, and from the PET images, we determined the tumor maximum standardized uptake value (SUVmax) of 2-deoxy-2-[18F]fluoro-D-glucose. Results: The SUVmax of malignant lesions significantly exceeded the SUVmax of benign (p < 0.005) and borderline lesions (p < 0.0005) that did not differ significantly. We found no significant correlation between measured HK or G6Pase activities and histological tumor type or SUVmax except that G6Pase activities were higher in malignant than borderline lesions (p < 0.05). Measured HK and G6Pase activities correlated inversely (p < 0.05). The slopes from the regression lines of the three correlations yielded positively correlated abscissa and ordinate intercepts, designated HKmax and G6Pasemax, respectively (r = 0.67, p < 0.0001). The positive correlations between the abscissa and ordinate intercepts with SUVmax had regression coefficients of r = 0.44, p < 0.05; and r = 0.39, p < 0.05, respectively. Conclusions: The results distinguished two ovarian cancer phenotypes, one with elevated HK activity and low G6Pase activity, and another with the opposite characteristics.

The partial volume effect (PVE) is considered as one of the major degrading factors impacting image quality and hampering the accuracy of quantitative PET imaging in clinical oncology. This effect is the consequence of the limited spatial resolution of whole-body PET scanners, which results in blurring of the generated images by the scanner's response function. A number of strategies have been devised to deal with partial volume effect. However, the lack of consensus on the clinical relevance of partial volume correction and the most appropriate technique to be used in the context of clinical oncology limited their application in clinical setting. This issue is debated in this commentary.

Purpose This systematic review and meta-analysis aimed to quantify the diagnostic performance of pancreatic venous sampling (PVS), selective pancreatic arterial calcium stimulation with hepatic venous sampling (ASVS), and 18F-DOPA positron emission tomography (PET) in diagnosing and localizing focal congenital hyperinsulinism (CHI). Procedures This systematic review and meta-analysis was conducted according to the PRISMA statement. PubMed, EMBASE, SCOPUS and Web of Science electronic databases were systematically searched from their inception to November 1, 2011. Using predefined inclusion and exclusion criteria, two blinded reviewers selected articles. Critical appraisal ranked the retrieved articles according to relevance and validity by means of the QUADAS-2 criteria. Pooled data of homogeneous study results estimated the sensitivity, specificity, likelihood ratios and diagnostic odds ratio (DOR). Results 18F-DOPA PET was superior in distinguishing focal from diffuse CHI (summary DOR, 73.2) compared to PVS (summary DOR, 23.5) and ASVS (summary DOR, 4.3). Furthermore, it localized focal CHI in the pancreas more accurately than PVS and ASVS (pooled accuracy, 0.82 vs. 0.76, and 0.64, respectively). Important limitations comprised the inclusion of studies with small sample sizes, high probability of bias and heterogeneity among their results. Studies with small sample sizes and high probability of bias tended to overestimate the diagnostic accuracy. Conclusions This systematic review and meta-analysis found evidence for the superiority of 18F-DOPA PET in diagnosing and localizing focal CHI in patients requiring surgery for this disease.

2-Deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake may be a useful surrogate marker for proliferation index, but the correlation has not always been clear-cut. Previous research by our group suggests that FDG-positron emission tomography (PET) is sensitive in detecting triple negative breast cancer. We therefore performed a pilot study to test if FDG uptake correlated with proliferation index in women with triple negative cancer. To determine whether proliferation index correlates with metabolic uptake of FDG in women with triple negative breast cancer, we performed a retrospective analysis correlating %Ki67 nuclear stain with tumor maximum standardized uptake values (SUVmax) in a group of 41 women, 22 with triple negative and 19 with non-triple negative breast cancer. As expected, [18F]-PET imaging was significantly more sensitive in detecting triple negative breast cancer than non-triple negative breast cancer, 95.5% vs 68.4% (p = 0.036). In general, SUVmax and %Ki67 nuclear stain values rise as histologic grade worsens. Histologic grade of triple negative breast cancer was more often poorly differentiated than non-triple negative cancer (p = 0.001). SUVmax correlated with %Ki67 nuclear staining in our entire cohort (spearman correlation = 0.485, p = 0.002). Moreover, this significant correlation appeared to be driven primarily by a subset of women with triple negative cancer (spearman correlation = 0.497, p = 0.019). Degree of tumor FDG uptake correlated significantly with proliferation index in women with triple negative breast cancer suggesting a potential role of FDG-PET in treatment response monitoring for this group of women. Future studies are necessary to define the role of PET imaging as a non-invasive means to monitor breast cancer treatment response in the neoadjuvant setting.

The early and accurate diagnosis of osteomyelitis in the diabetic foot is essential to provide appropriate treatment and obviate long-term complications of the disease. The currently employed non-invasive imaging modalities such as plain film radiography (PFR) lack the sensitivity to accurately exclude osteomyelitis, while magnetic resonance imaging (MRI) is limited by its low specificity and contraindications in certain patients. Therefore, accurate non-invasive detection of osteomyelitis in the diabetic foot remains a challenge. [18F]-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) has been proven useful in other settings to detect infection. In this ongoing prospective study, we assessed the diagnostic performance of FDG-PET to diagnose osteomyelitis in the diabetic foot and compared it with that of MRI and PFR. Patients who met the prespecified criteria for complicated diabetic foot underwent FDG-PET, MRI, and PFR of the feet. Each imaging study was then interpreted in a blinded fashion for presence of osteomyelitis or other abnormalities. The gold standard for diagnosis in each patient was based on surgical, microbiological, and clinical follow-up results. One hundred ten consecutive patients have been enrolled to date into this prospective project. FDG-PET correctly diagnosed osteomyelitis in 21 of 26 patients and correctly excluded it in 74 of 80, with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 81%, 93%, 78%, 94%, and 90%, respectively. MRI correctly diagnosed osteomyelitis in 20 of 22 and correctly excluded it in 56 of 72, with sensitivity, specificity, PPV, NPV, and accuracy of 91%, 78%, 56%, 97%, and 81%, respectively. PFR correctly diagnosed osteomyelitis in 15 of 24 and correctly excluded it in 65 of 75, with sensitivity, specificity, PPV, NPV, and accuracy of 63%, 87%, 60%, 88%, and 81%, respectively. FDG-PET is a highly specific imaging modality for the diagnosis of osteomyelitis in diabetic foot and, therefore, should be considered to be a useful complimentary imaging modality with MRI. In the setting where MRI is contraindicated, the high sensitivity and specificity of FDG-PET justifies its use after a negative or inconclusive PFR to aid an accurate diagnosis.

The present study was undertaken to investigate the significance of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) uptake in the intercostal muscles (ICM) and prominent visualization of right ventricle (RV) in FDG-positron emission tomography (PET) scans and its implications. Patients identified to have FDG uptake in the ICM with or without prominent visualization of the RV either incidentally or in the background of an existing explanatory cause at the time of FDG-PET studies were included in this retrospective study. These patients had undergone FDG-PET either for ruling out malignancy or for disease monitoring purposes in setting a proven malignancy. We reviewed the clinical and investigational records (including computed tomography [CT] thorax, chest X-ray, 2-D echo and pulmonary function tests, and arterial blood gas analysis) of the group with incidental FDG uptake for revelation of a pathology explaining such uptake. A total of 14 cases with 16 FDG-PET studies were identified from the retrospective examination of case records. One patient had three FDG-PET at different time points of his disease course. The patient population included 13 males and one female with age range 46–88 years. The patients were classified into two groups: (1) cases with isolated ICM uptake (n = 10); (2) cases with both ICM and RV uptake (n = 4). Among 10 patients with isolated ICM uptake, in six patients it was a serendipitous observation, whereas four patients had existing explanatory cause at the time of FDG-PET. The causes found to be associated included COPD, asthma, recent heart failure, interstitial lung disease (post external radiotherapy) and pulmonary embolism, atelectasis with pleural effusion. In all four cases with associated RV uptake, there was evidence of pulmonary hypertension (PH). Among these, in one patient this was a serendipitous observation. He had evidence of interstitial lung disease (ILD) in CT thorax, and 2-D echo showed moderate PH. The remaining three patients had cor pulmonale secondary to COPD, pneumoconiosis, and Swyer James Syndrome with associated severe PH. The SUVmax ratio of the RV-to-LV free wall ranged from 0.53 to 1.04 in the cases with prominent RV uptake. One patient had multiple FDG-PET studies and have shown reduction of RV uptake in the last scan consistent with the clinical impression of improvement of cor pulmonale. Both intercostal muscle and prominent RV uptake in FDG-PET can be associated with a spectrum of causes (including both obstructive and restrictive airway diseases) that lead to breathing exertion. These are important markers, which could signify underlying pulmonary disease and pulmonary hypertension, respectively. Associated prominent RV uptake strongly indicates presence of pulmonary hypertension and the uptake in the right heart can subserve a valuable surrogate marker in the treatment- monitoring scenario of a known PH.

This study was conducted to assess the effect of breast density, age, and menopausal status on the 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG) uptake in normal breast tissue by quantitative standardized uptake values (SUV).A total of 96 patients (premenopausal 54; postmenopausal 42) with histologically proven unilateral breast cancer who underwent FDG-positron emission tomography (PET) scans for staging were included in this study. The median age was 52+/-11 years (range 32-79 years). Fifty-nine patients had grade III or IV mammographic density (dense breast), whereas 37 patients had grade I or II breast density (nondense) according to the ACR Lexicon criteria. In the present study, we analyzed maximum and average SUVs for contralateral normal breast.Maximum and average SUVs for normal dense breasts were 1.02+/-0.30 and 0.84+/-0.27, respectively. Similar values for the nondense breasts were 0.66+/-0.24 and 0.53+/-0.23, respectively. Both maximum and average SUVs of dense breasts were significantly higher than those of nondense breasts (p0.001). There was no significant difference in SUVs of nipple in patients with dense and nondense breasts. There was no significant effect of age and menopausal status on SUVs of normal breast. However, there were trends of negative relationship, i.e., decreasing SUVs with increasing age.There was a significant difference in SUVs between the dense and nondense normal breast. However, the maximum SUVs in the dense breasts were well below the threshold of 2.5, a widely used cutoff value for malignancy. Menopausal status and age do not significantly affect the uptake of FDG.

The aim of this study is to assess a software-based method with semiautomated correction for partial volume effect (PVE) to quantify the metabolic activity of pulmonary malignancies in patients who underwent non-gated and respiratory-gated 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG)-positron emission tomography (PET)/x-ray computed tomography(CT).The study included 106 lesions of 55 lung cancer patients who underwent respiratory-gated FDG-PET/CT for radiation therapy treatment planning. Volumetric PET/CT parameters were determined by using 4D PET/CT and non-gated PET/CT images. We used a semiautomated program employing an adaptive contrast-oriented thresholding algorithm for lesion delineation as well as a lesion-based partial volume effect correction algorithm. We compared respiratory-gated parameters with non-gated parameters by using pairwise comparison and interclass correlation coefficient assessment. In a multivariable regression analysis, we also examined factors, which can affect quantification accuracy, including the size of lesion and the location of tumor.This study showed that quantification of volumetric parameters of 4D PET/CT images using an adaptive contrast-oriented thresholding algorithm and 3D lesion-based partial volume correction is feasible. We observed slight increase in FDG uptake by using PET/CT volumetric parameters in comparison of highest respiratory-gated values with non-gated values. After correction for partial volume effect, the mean standardized uptake value (SUVmean) and total lesion glycolysis (TLG) increased substantially (p value0.001). However, we did not observe a clinically significant difference between partial volume corrected parameters of respiratory-gated and non-gated PET/CT scans. Regression analysis showed that tumor volume was the main predictor of quantification inaccuracy caused by partial volume effect.Based on this study, assessment of volumetric PET/CT parameters and partial volume effect correction for accurate quantification of lung malignant lesions by using respiratory non-gated PET images are feasible and it is comparable to gated measurements. Partial volume correction increased both the respiratory-gated and non-gated values significantly and appears to be the dominant source of quantification error of lung lesions.

Advances in positron emission tomography (PET) imaging have provided opportunities to develop radiotracers specific for imaging insulin-producing pancreatic β-cells. However, a host of lingering questions should be addressed before these radiotracers are advocated for noninvasive quantification of β-cell mass (BCM) in vivo in the native pancreas. We provide an overview of tetrabenazine-based PET tracers developed to image and quantify BCM and discuss several theoretical, technical, and biological limitations of applying these tracers in clinical practice. VMAT2, a transporter protein expressed on pancreatic β-cells, has been advocated as a promising target for PET imaging tracers, such as dihydrotetrabenazine. However, the lack of radiotracer specificity for these proteins hampers their clinical application. Another important argument against their use is a striking discrepancy between radiotracer uptake and BCM in subjects with type I diabetes mellitus and healthy controls. Additionally, technical issues, such as the finite spatial resolution of PET, partial volume effects, and movement of the pancreas during respiration, impede PET imaging as a viable option for BCM quantification in the foreseeable future. The assertion that BCM can be accurately quantified by tetrabenazine derived β-cell-specific radiotracers as density per unit volume of pancreatic tissue is not justifiable at this time. The fallacy of these claims can be explained by technical as well as biological facts that have been disregarded and ignored in the literature.

This study aims to evaluate dynamic 2-deoxy-2-[18F]fluoro-d-glucose (FDG) uptake in normal tissues. Thirty male patients underwent FDG positron emission tomography (PET)/computed tomography imaging at 1, 2, and 3 h after tracer injection. Standardized uptake values (SUV) were obtained in regions of interest of normal tissues. The aorta (blood pool), liver, and spleen FDG activity demonstrated significantly and continuously decreased activity from 1 to 2 and 2 to 3 h, while FDG uptake in the lungs, pancreas, lymph nodes, and skeletal muscle decreased from 1 to 2 h only. In contrast, the left ventricular myocardium demonstrated two patterns of dynamic changes: myocardium with higher FDG uptake (SUVmax ≥ 3.25) on the initial images had more remarkable increased activity on the delayed images, while myocardium with lower FDG uptake (SUVmax

There have been several endeavors made to investigate the potential role of 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography (FDG-PET) (and tracers) and PET-computed tomography imaging in various benign disorders, particularly those related to thoracic structures. These various conditions can be broadly categorized into three groups: (a) infectious diseases (mycobacterial, fungal, bacterial infection), (b) active granulomatous disease such as sarcoidosis, and (c) other non-infectious/inflammatory conditions or proliferative disorders (e.g., radiation pneumonitis, post-lung transplant lymphoproliferative disorders, occupational pleuropulmonary complications, and post-surgical conditions), all of which can demonstrate varying degrees of FDG uptake on PET scans based upon the degree of inflammatory activity. This article reviews the current state of this very important application of FDG-PET imaging.