Does the association of 18F-FDG uptake intensity and lesion topography reveal histological phenotype and tumor differentiation in esophageal cancer?

In daily clinical practice, the esophageal squamous cell cancer (ESCC) is considered to be more (18)F-FDG avid than adenocarcinoma (EAD). To date, the few studies concerning the existence of a real metabolic difference based on esophageal cancer (EC) histology, show divergent and not definitive results. A retrospective analysis of (18)F-FDG PET/CT of 87 patients with ESCC and EAD was performed to investigate the role played by both histopathological subtype and tumor differentiation in the characterization of glucose metabolic profile of EC. Esophageal squamous cell cancer was well differentiated (WD) in 42 cases and poorly differentiated (PD) in 12 patients. Twenty-one of the 33 patients had WD EAD, while 12 had a PD EAD. The (18)F-FDG maximal standardized uptake value (SUV(max)) was determined for all lesions and used for inter and intra-group comparison. In ESCC, the SUV(max) ranged from 4 to 31 with a mean value of 16±6. In EAD, the SUV(max) ranged from 2 to 25 with a mean value of 10±6. A statistically significant difference (P<0.0001) was found between ESCC and EAD. According to histological classification and tumor differentiation, we obtained the following results: a) the SUV(max) values of WD ESCC and WD EAD were 17±5 (range: 7-31) and 7±3 (range: 2-12) respectively (P<0.00001), b) the SUV(max) values of PD ESCC and PD EAD were 11±4 (range: 4-19) and 17±6 (range: 7-25) respectively (P<0.05). Moreover, a statistically significant difference of SUV(max) values was found between WD and PD ESCC (P<0.005) as well as between WD and PD differentiated EAD (P<0.0001). In order to predict tumor histology (ESCC, EAD) from both SUV(max) and lesion location, a multivariate discriminant analysis was performed on the whole population with a resulting diagnostic accuracy equal to 82% (P<0.00001). In conclusion, we provide additional arguments about (18)F-FDG uptake difference between ESCC and EAD as well as between poorly and well-differentiated forms of both EC histological subtypes.     

Selective intra-arterial administration of 18F-FDG to the rat brain — effects on hemispheric uptake

Introduction

The purpose of this study was to investigate the radioligand uptake and iodine contrast distribution in the intra- and extracranial circulation of the rat, after intra-arterial injections to the common carotid artery and different parts of the internal carotid artery.

Methods

All animal experiments were carried out in accordance with Karolinska Institutet’s guidelines and were approved by the local laboratory animal ethics committee. We used clinical neurointerventional systems to place microcatheters in the extra- or intracranial carotid artery of 15 Sprague–Dawley rats. Here, injection dynamics of iodine contrast was assessed using digital subtraction angiography. Maintaining the catheter position, the animals were placed in a micro PET and small-animal positron emission tomography (PET) was used to analyze injections [2-¹⁸F]-2-fluoro-2-deoxy-d-glucose (¹⁸F-FDG).

Results

Microcatheters had to be placed in the intracranial carotid artery (iICA) for the infusate to distribute to the brain. Selective injection via the iICA resulted in a 9-fold higher uptake of ¹⁸F-FDG in the injected hemisphere (p?<?0.005) compared to both intravenous and more proximal carotid artery injections. Furthermore, selective injection gave a dramatically improved contrast between the brain and extracranial tissue.

Conclusion

Intra-arterial injection increases the cerebral uptake of a radiotracer dramatically compared to systemic injection. This technique has potential applications for endovascular treatment of malignancies allowing intra-interventional modifications of injection strategy, based on information on tumor perfusion and risk to surrounding normal parenchyma. Furthermore the technique may increase diagnostic sensitivity and avoid problems due to peripheral pharmacological barriers and first passage metabolism of labile tracers.     

Abnormally increased uptake of 18F-FDG in the forearm and hand following intra-arterial injection — hot forearm and hot hand signs

The aim of this study is to describe the appearance of intra-arterial administration of 18F-fluorodeoxyglucose (18F-FDG). The effect of this finding on the standard uptake values (SUVs) is also briefly discussed. Three cases of 18F-FDG positron emission tomography (PET) scans, detected over 2 years (2004–2006), with different presentations producing hot forearm and hot hand signs are described. It was shown that intra-arterial injections of 18F-FDG producing “the hot forearm sign” and the hot hand sign” are similar to the glove pattern of uptake noted following intra-arterial administration of technetium-99m methylene diphosphonate. Following intra-arterial injection, uptake of 18F-FDG is accentuated by hypoxia and exercise. A comparison is also made with the pattern of soft-tissue uptake seen following true intravenous injections with similar pre-injection vein enhancement techniques to the intra-arterial injections. Evaluation of the maximum intensity projection (MIP) and transaxial PET/CT fusion images of the arm, forearm and hand helps to confirm the diagnosis. Hands are often not included in PET/CT imaging and therefore cases might be missed. In conclusion, intra-arterial injection of 18F-FDG produces a “hot forearm sign” and “hot hand sign”. Hands are often not included in PET/CT imaging, and therefore the presence of hot forearm sign should suggest further investigation. It should be mentioned in the radiology report, as it may alter the sensitivity and specificity of the SUV value.Inadvertent intra-arterial injections of various radiopharmaceuticals are well known. A bone imaging agent, such as technetium-99m (⁹⁹Tc^m) methylene diphosphonate (MDP), when injected into the artery at the antecubital fossa or wrist results in a “glove phenomenon” or “glove-like pattern” of distribution of radioactivity [1–4]. Here, the intra-arterial injection of 18F-fluorodeoxyglucose (18F-FDG) and its uptake in the tissues distal to the injection are described.     

Biodistribution and breast tumor uptake of 16α-[18F]-fluoro-17β-estradiol in rat

To evaluate the usefulness of 16alpha-[18F]-fluoro-17beta-estradiol (FES) for the assessment of estrogen receptor (ER), we examined the tissue distribution and kinetics of FES in immature female Sprague-Dawley rats and then examined FES uptake in rat breast tumors induced by 7,12-dimethylbenz(a) anthracene (DMBA). The FES uptake by the uterus, an ER-rich tissue, was highly selective and it was 3.34 +/- 0.79%ID/g at 60 minutes and 1.57 +/- 0.57%ID/g at 120 minutes after injection. The FES uptakes in ER-negative tissues were 0.12 +/- 0.05%ID/g or less and 0.05 +/- 0.03%ID/g or less, respectively. Coadministration of unlabeled beta-estradiol showed marked depression of uterine FES uptake. The FES uptake by rat breast tumors was 0.14 +/- 0.06%ID/g at 60 min and 0.12 +/- 0.09%ID/g at 120 min. The FES uptake by rat breast tumors correlated with the ER concentration (r = 0.45, p < 0.05). In conclusion, these results suggest that the FES uptake by tissue is mainly ER mediated and FES is thus useful for detecting ER positive breast tumors.     

Extensive skeletal muscle uptake of 18F-FDG: relation to immunosuppressants?

A case of gross skeletal muscle uptake of 18F-FDG during PET is described. The clinical context of immunosuppression after heart and lung transplantation and the absence of any other known association make the former a likely etiologic factor.     

Prognostic value of 18 F-FDG uptake by regional lymph nodes on pretreatment PET/CT in patients with resectable colorectal cancer

Purpose

We evaluated the ability of pretreatment ¹⁸?F-FDG uptake by regional lymph nodes to predict the survival of patients with resectable colorectal cancer.

Methods

The records of 78 patients with AJCC stage III colorectal cancer (pathologically confirmed node-positive disease without evidence of distant metastasis) treated with surgery and adjuvant chemotherapy were retrospectively reviewed. The maximum standardized uptake values of the primary tumor (SUVp) and regional lymph nodes (SUVn) were measured by pretreatment ¹⁸?F-FDG PET/CT. The ROC curve analyses and the Cox proportional hazard model were used to analyze whether SUVp, SUVn, and clinicopathologic parameters could predict disease-free survival.

Results

Although there were no significant differences between the median SUVp in the event group and that in the non-event group, the median SUVn was significantly higher in the event group (1.7) than in the non-event group (0.8, p?=?0.023). Based on the ROC curve analysis, SUVn predicted the event for disease-free survival (AUC?=?0.668, p?=?0.02) with the optimal criterion, sensitivity, specificity, and accuracy of?>?1.2, 71 %, 63 %, and 65 %, respectively. However, SUVp did not predict disease-free survival (AUC?=?0.570, p?=?0.349). Univariate analysis revealed that SUVn (p?=?0.011) and venous invasion (p?=?0.016) were associated with disease-free survival, but pathologic N stage was not (p?=?0.09). By multivariate analysis, only SUVn?>?1.2 independently shortened the disease-free survival (relative risk, 2.97; 95 % CI, 1.14–7.74, p?=?0.026).

Conclusion

SUVn before surgery may be a useful prognostic marker in patients with AJCC stage III colorectal cancer.     

Glucose uptake of the muscle and adipose tissues in diabetes and obesity disease models: evaluation of insulin and β3-adrenergic receptor agonist effects by <Superscript>18</Superscript>F-FDG

Objective

One of the major causes of diabetes and obesity is abnormality in glucose metabolism and glucose uptake in the muscle and adipose tissue based on an insufficient action of insulin. Therefore, many of the drug discovery programs are based on the concept of stimulating glucose uptake in these tissues. Improvement of glucose metabolism has been assessed based on blood parameters, but these merely reflect the systemic reaction to the drug administered. We have conducted basic studies to investigate the usefulness of glucose uptake measurement in various muscle and adipose tissues in pharmacological tests using disease-model animals.

Methods

A radiotracer for glucose, ¹⁸F-2-deoxy-2-fluoro-d-glucose (¹⁸F-FDG), was administered to Wistar fatty rats (type 2 diabetes model), DIO mouse (obese model), and the corresponding control animals, and the basal glucose uptake in the muscle and adipose (white and brown) tissues were compared using biodistribution method. Moreover, insulin and a β3 agonist (CL316,243), which are known to stimulate glucose uptake in the muscle and adipose tissues, were administered to assess their effect. ¹⁸F-FDG uptake in each tissue was measured as the radioactivity and the distribution was confirmed by autoradiography.

Results

In Wistar fatty rats, all the tissues measured showed a decrease in the basal level of glucose uptake when compared to Wistar lean rats. On the other hand, the same trend was observed only in the white adipose tissue in DIO mice, while brown adipose tissue showed increments in the basal glucose uptake in this model. Insulin administration stimulated glucose uptake in both Wistar lean and fatty rats, although the responses were inhibited in Wistar fatty rats. The same tendency was shown also in control mice, but clear increments in glucose uptake were not observed in the muscle and brown adipose tissue of DIO mice after insulin administration. β3 agonist administration showed the similar trend in Wistar lean and fatty rats as insulin, while the responses were inhibited in the adipose tissues of Wistar fatty rats.

Conclusion

A system to monitor tissue glucose uptake with ¹⁸F-FDG enabled us to detect clear differences in basal glucose uptake between disease-model animals and their corresponding controls. The responses in the tissues to insulin or β3 agonist could be identified. Taken as a whole, the biodistribution method with ¹⁸F-FDG was confirmed to be useful for pharmacological evaluation of anti-diabetic or anti-obesity drugs using disease-model animals.

     

Do high glucose levels have differential effect on FDG uptake in inflammatory and malignant disorders?

BACKGROUND: The association of hyperglycaemia with reduced fluorodeoxyglucose (FDG) uptake by tumour cells is well established. Therefore, it is standard practice that all patients must fast for at least several hours prior to FDG positron emission tomography (PET) imaging. However, the effect of hyperglycaemia on FDG uptake by inflammatory and infectious lesions is unknown. The aim of this study was to investigate this important issue. METHODS: For in vitro studies human mononuclear cells were isolated from 12 normal volunteers and FDG uptake was determined in medium containing differing concentrations of glucose. FDG uptake by human mesothelioma cells was also measured for comparison. For studies involving patients, 416 FDG PET scans of patients with confirmed malignancy (n=321) or benign lesions (n=95) were reviewed retrospectively. The relationship between serum glucose level and FDG uptake by the lesions was assessed utilizing the standardized uptake value (SUV) technique. RESULTS: In the in vitro studies, while FDG uptake by mesothelioma cells decreased as glucose concentration increased, there was no differential uptake of FDG uptake by mononuclear cells at glucose concentrations less than 250 mg x dl(-1). In clinical patients, FDG uptake by malignant lesions was slightly, but negatively affected by serum glucose level (r= -0.21, P<0.01) (glucose range 49-187 mg x dl(-1)). In contrast, FDG uptake by inflammatory lesions was positively associated with serum glucose level (r=0.43, P<0.01) (glucose range 54-215 mg x dl(-1)). DISCUSSION AND CONCLUSION: While the degree of FDG uptake is primarily influenced by the nature of the underlying lesion, serum glucose concentration appears to have a small effect on FDG uptake, which differs between malignant disorders and inflammatory processes. Our data suggest that below a certain level, elevated glucose concentration might not have a negative effect on FDG uptake in inflammatory cells, contrary to that observed in malignant disorders.     

Suppression of myocardial 18F-FDG uptake with a preparatory “Atkins-style” low-carbohydrate diet

Objectives

Physiological myocardial uptake of 18F-FDG during positron emission tomography can mask adjacent abnormal uptake in mediastinal malignancy and inflammatory cardiac diseases. Myocardial uptake is unpredictable and variable. This study evaluates the impact of a low-carbohydrate diet in reducing myocardial FDG uptake.

Method

Patients attending for clinically indicated oncological FDG PET were asked to have an “Atkins-style” low-carbohydrate diet (less than 3 g) the day before examination and an overnight fast. A total of 120 patients following low-carbohydrate diet plus overnight fast were compared with 120 patients prepared by overnight fast alone. Patients having an Atkins-style diet also completed a diet compliance questionnaire. SUV_max and SUV_mean for myocardium, blood pool and liver were measured in both groups.

Results

Myocardial SUV_max fell from 3.53?±?2.91 in controls to 1.77?±?0.91 in the diet-compliant group. 98 % of diet-compliant patients had a myocardial SUV_max less than 3.6 compared with 67 % of controls. Liver and blood pool SUV_max rose from 2.68?±?0.49 and 1.82?±?0.30 in the control group to 3.14?±?0.57 and 2.06?±?0.30.

Conclusion

An Atkins-style diet the day before PET, together with an overnight fast, effectively suppresses myocardial FDG uptake.

Key Points

? Low-carbohydrate diet (LCD) the day before PET suppresses myocardial FDG uptake. ? LCD before PET increases liver and blood pool SUV _max and SUV _mean . ? Suppression of myocardial uptake may improve PET imaging of thoracic disease. ? Suppression of myocardial uptake may help imaging cardiac inflammatory disease with PET.     

The effect of renal artery stenting on hypertension and renal function in patients with atherosclerotic renovascular disease

IntroductionAtheroscleroticrenal arterystenosisisassociatedwithhypertension ,progressivelossofrenalfunctionandrecurrentpulmonaryedema [1 3].Althoughsurgicalrevascularizationhasbeenshowntoimprovebloodpressurecontrol,preserveorstabilizerenalfunction [4 ],andreverseend stagerenalfailure[5 ],itsmorbidityandmortalityrateshavebeenhigherthanthoseofstentrevascularization [6 ].Stentrevascularizationhasbeenshowntobesuperiorto“balloononly”angioplastyandsurgicalrevascularization [7].Thisstudyevaluatesth…     

Radiosensitizing effect of epothilone?B on human epithelial cancer cells

Background

A combined modality treatment employing radiation and chemotherapy plays a central role in the management of solid tumors. In our study, we examined the cytotoxic and radiosensitive effect of the microtubule stabilizer epothilone?B on two human epithelial tumor cell lines in vitro and its influence on the microtubule assembly.

Methods

Cancer cells were treated with epothilone?B in proliferation assays and in combination with radiation in colony-forming assays. For the analysis of ionizing radiation-induced DNA damage and the influence of the drug on its repair a ??H2AX foci assay was used. To determine the effect of epothilone?B on the microtubule assembly in cells and on purified tubulin, immunofluorescence staining and tubulin polymerization assay, respectively, were conducted.

Results

Epothilone?B induced a concentration- and application-dependent antiproliferative effect on the cells, with IC₅₀?values in the low nanomolar range. Colony forming assays showed a synergistic radiosensitive effect on both cell lines which was dependent on incubation time and applied concentration of epothilone?B. The ??H2AX assays demonstrated that ionizing radiation combined with the drug resulted in a concentration-dependent increase in the number of double-strand breaks and suggested a reduction in DNA repair capacity. Epothilone?B produced enhanced microtubule bundling and abnormal spindle formation as revealed by immunofluorescence microscopy and caused microtubule formation from purified tubulin.

Conclusion

The results of this study showed that epothilone?B displays cytotoxic antitumor activity at low nanomolar concentrations and also enhances the radiation response in the tumor cells tested; this may be induced by a reduced DNA repair capacity triggered by epothilone?B. It was also demonstrated that epothilone?B in fact targets microtubules in a more effective manner than paclitaxel.     

The effect of instructions on postural–suprapostural interactions in three working memory tasks

Examining postural control while simultaneously performing a cognitive, or suprapostural task, has shown a fairly consistent trend of improving postural control in young healthy adults and provides insight into postural control mechanisms used in everyday life. However, the role of attention driven by explicit verbal instructions while dual-tasking is less understood. Therefore, the purpose of this investigation is to determine the effects of explicit verbal instructions on the postural–suprapostural interactions among various domains of working memory. A total of 22 healthy young adults with a heterogeneous history of ankle sprains volunteered to participate (age: 22.2 ± 5.1 years; n = 10 history of ankle sprains, n = 12 no history). Participants were asked to perform single-limb balance trials while performing three suprapostural tasks: backwards counting, random number generation, and the manikin test. In addition, each suprapostural task was completed under three conditions of instruction: no instructions, focus on the postural control task, focus on the suprapostural task. The results indicate a significant effect of instructions on postural control outcomes, with postural performance improving in the presence of instructions across all three cognitive tasks which each stress different aspects of working memory. Further, postural–suprapostural interactions appear to be related to the direction or focus of an individual’s attention as instructions to focus on the suprapostural task resulted in the greatest postural control improvements.Thus, attention driven by explicit verbal instructions influence postural–suprapostural interactions as measured by a temporal–spatial postural control outcome, time-to-boundary, regardless of the suprapostural task performed.     

The effect of abnormality-prevalence expectation on naïve observer performance and visual search

ObjectiveTo measure the effect of abnormality-prevalence expectation on naïve observer performance during lesion detection on chest radiographs.MethodsA multi-reader, fixed-case receiver-operating characteristic (ROC) and eye-position analysis study to assess the effect of prevalence expectation on observer performance was conducted. Sixteen diagnostic radiography students (naïve observers) were divided into four prevalence expectation groups (four in each group) and each was asked to interpret thirty (15 abnormal) postero-anterior (PA) identical chest image sets twice to decide if pulmonary nodular lesions were present. Prior to each viewing they were told that the images contained a specific number of abnormal images: group 1: 9 & 15; group 2: 15 & 22; group 3: 9 & 22; group 4:15 & 15.ResultsROC-analysis demonstrated that no significant effect could be measured as a function of prevalence (p > 0.05). However, sensitivity analysis showed a significant change in Group 3 (p = 0.0237). Eye-positional analysis showed one significant change, which was found in Group 1 for mean fixation duration on a lesion (p = 0.0458).ConclusionOverall, the findings of this study showed evidence that the rudimentary performance of naïve observers is altered due to changing prevalence expectation rates.