18F-FDG-PET/MRI in preoperative staging of oesophageal and gastroesophageal junctional cancer.

AIM: To evaluate integrated 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/magnetic resonance imaging (MRI), in comparison with the standard technique, integrated 18F-FDG-PET/computed tomography (CT), in preoperative staging of oesophageal or gastroesophageal junctional cancer. MATERIALS AND METHODS: In the preoperative staging of 16 patients with oesophageal or gastroesophageal junctional cancer, 18F-FDG-PET/MRI was performed immediately following the clinically indicated 18F-FDG-PET/CT. MRI-sequences included T1-weighted fat-water separation (Dixon's technique), T2-weighted, diffusion-weighted imaging (DWI), and gadolinium contrast-enhanced T1-weighted three-dimensional (3D) imaging. PET was performed with 18F-FDG. Two separate teams of radiologists conducted structured blinded readings of 18F-FDG-PET/MRI or 18F-FDG-PET/CT, which were then compared regarding tumour measurements and characteristics as well as assessment of inter-rater agreement (Cohen's kappa) for the clinical tumour, nodal and metastatic (TNM) stage. RESULTS: There were no medical complications. Comparison of tumour measurements revealed high correlations without significant differences between modalities. The maximum standardised uptake value (SUVmax) values of the primary tumour with 18F-FDG-PET/MRI had excellent correlation to those of 18F-FDG-PET/CT (0.912, Spearman's rho). Inter-rater agreement between the techniques regarding T-stage was only fair (Cohen's kappa, 0.333), arguably owing to relative over-classification of the T-stage using 18F-FDG-PET/CT. Agreements in the assessment of N- and M-stage were substantial (Cohen's kappa, 0.849 and 0.871 respectively). CONCLUSION: Preoperative staging with 18F-FDG-PET/MRI is safe and promising with the potential to enhance tissue resolution in the area of interest. 18F-FDG-PET/MRI and 18F-FDG-PET/CT correlated well for most of the measured values and discrepancies were seen mainly in the assessment of the T-stage. These results facilitate further studies investigating the role of 18F-FDG-PET/MRI in, e.g., predicting or determining the response to neoadjuvant therapy.

Medial temporal lobe atrophy ratings in a large 75-year-old population-based cohort: gender-corrected and education-corrected normative data.

OBJECTIVES: To find cut-off values for different medial temporal lobe atrophy (MTA) measures (right, left, average, and highest), accounting for gender and education, investigate the association with cognitive performance, and to compare with decline of cognitive function over 5 years in a large population-based cohort. METHODS: Three hundred and ninety 75-year-old individuals were examined with magnetic resonance imaging of the brain and cognitive testing. The Scheltens's scale was used to assess visually MTA scores (0-4) in all subjects. Cognitive tests were repeated in 278 of them after 5 years. Normal MTA cut-off values were calculated based on the 10th percentile. RESULTS: Most 75-year-old individuals had MTA score ≤2. Men had significantly higher MTA scores than women. Scores for left and average MTA were significantly higher in highly educated individuals. Abnormal MTA was associated with worse results in cognitive test and individuals with abnormal right MTA had faster cognitive decline. CONCLUSION: At age 75, gender and education are confounders for MTA grading. A score of ≥2 is abnormal for low-educated women and a score of ≥2.5 is abnormal for men and high-educated women. Subjects with abnormal right MTA, but normal MMSE scores had developed worse MMSE scores 5 years later. KEY POINTS: • Gender and education are confounders for MTA grading. • We suggest cut-off values for 75-year-olds, taking gender and education into account. • Males have higher MTA scores than women. • Higher MTA scores are associated with worse cognitive performance.

Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obesity.

BACKGROUND: Bile acid (BA) synthesis is regulated by BA signalling in the liver and by fibroblast growth factor 19 (FGF19), synthesized and released from the intestine. In morbid obesity, faecal excretion and hepatic synthesis of BAs and cholesterol are strongly induced and caloric restriction reduces their faecal excretion considerably. We hypothesized that the high intestinal food mass in morbidly obese subjects promotes faecal excretion of BAs and cholesterol, thereby creating a shortage of both BAs and cholesterol in the liver. METHODS: Ten morbidly obese women (BMI 42 ± 2.6 kg m-2 ) were monitored on days 0, 3, 7, 14 and 28 after beginning a low-calorie diet (800-1100 kcal day-1 ). Serum was collected and liver size and fat content determined. Synthesis of BAs and cholesterol was evaluated from serum markers, and the serum levels of lipoproteins, BAs, proprotein convertase subtilisin/kexin type 9 (PCSK9), insulin, glucose and FGF19 were monitored. Fifty-four nonobese women (BMI <25 kg m-2 ) served as controls. RESULTS: At baseline, synthesis of both BAs and cholesterol and serum levels of BAs and PCSK9 were elevated in the obese group compared to controls. Already after 3 days on a low-calorie diet, BA and cholesterol synthesis and serum BA and PCSK9 levels normalized, whereas LDL cholesterol increased. FGF19 and triglyceride levels were unchanged, and liver volume was reduced by 10%. CONCLUSIONS: The results suggest that hepatic BAs and cholesterol are deficient in morbid obesity. Caloric restriction rapidly counteracts these deficiencies, normalizing BA and cholesterol synthesis and circulating PCSK9 levels, indicating that overproduction of cholesterol in enlarged peripheral tissues cannot explain this phenotype. We propose that excessive food intake promotes faecal loss of BAs and cholesterol contributing to their hepatic deficiencies.

Validation of 3 T MRI including diffusion-weighted imaging for nodal staging of newly diagnosed intermediate- and high-risk prostate cancer.

AIM: To prospectively validate 3 T magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) for preoperative lymph node (LN) staging in a clinical setting, in intermediate- and high-risk prostate cancer (PCa) patients using laparoscopic extended LN dissection (ePLND) as the reference standard. MATERIALS AND METHODS: Between August 2011 and May 2013, 40 newly diagnosed intermediate and high-risk PCa patients underwent preoperative LN staging with 3 T MRI DWI using histopathology of ePLND as the reference standard. The sensitivity, specificity, and accuracy of MRI DWI were calculated. A subgroup analysis of proven LN-positive patients was made to investigate differences in PSA, Gleason score, number, and size of LN metastases, estimated risk of LN involvement, and if curative treatment was indicated, between the true-positive and the false-negative groups. RESULTS: A total of 728 LN were harvested from six anatomical regions per patient (external, obturator, internal) with a mean number of 18 LNs per patient (range 11-40). Twenty patients had histologically proven LN-positive disease. MRI DWI was true positive in 11 patients, false negative in nine patients, false positive in two patients, and true negative in 18 patients, resulting in 90% specificity, 55% sensitivity, and 72.5% accuracy. The true-positive patients had significantly more involved LNs (mean 6.9 versus 2.7, p=0.017), with larger diameter (mean 12.3 versus 5.2 mm, p=0.048) and fewer were treated with curative intent (six versus nine, p=0.03), compared with the false-negative group. CONCLUSION: MRI DWI LN staging has a low sensitivity but high specificity. The true-positive patients have a considerably higher burden of LN metastases compared to false-negative patients.

Comparison between MRI and CT in prediction of peritoneal carcinomatosis index (PCI) in patients undergoing cytoreductive surgery in relation to the experience of the radiologist.

BACKGROUND: To compare CT and MRI for peritoneal carcinomatosis index (PCI) assessment and to compare assessments made by the radiologist based on their experiences. METHOD AND MATERIALS: MRI and CT of abdomen and pelvis were performed on 39 prospectively followed by surgery directly. Two blinded radiologists with different experience levels evaluated PCI separately on different occasions on 19 cases initially and later on the remaining 20. The agreement between the radiologists' assessment and surgical findings in total and per site were recorded. RESULTS: Total PCI: The experienced radiologist was able to assess total tumor burden correctly on both CT and MRI (kappa = 1.0). For the inexperienced radiologist the assessment was better on CT (kappa = 0.73) compared to MRI (kappa = 0.58). Different sites: The experienced radiologist showed high agreement with kappa = 0.77 for MRI and 0.80 for CT. Corresponding figures were 0.39 and 0.60 for the inexperienced radiologist. For the second phase the agreement levels increased for the inexperienced radiologist increased to 0.80 and 0.70, respectively. CONCLUSION: CT and MRI are equal when read by experienced radiologist. CT shows better results when read by an inexperienced radiologist compared to MRI, however the results of the latter can easily be improved.

Whole-body diffusion-weighted MRI and (18)F-FDG PET/CT can discriminate between different lymphoma subtypes.

AIM: To determine whether combined 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) positron-emission tomography (PET)/computed tomography (CT) and diffusion-weighted imaging (DWI) can be used for characterisation of different lymphoma subtypes, i.e., indolent versus aggressive lymphoma, and also to assess the prognostic value of different quantitative parameters of whole-body (WB) DWI and (18)F-FDG PET/CT. MATERIALS AND METHODS: Pre-therapeutic WB magnetic resonance imaging (MRI) including DWI and (18)F-FDG PET/CT were performed in lymphoma patients. Different quantitative DWI and (18)F-FDG PET/CT parameters were evaluated for characterisation of different lymphoma subtypes. These parameters were also correlated, both separately and in combination, against overall survival (OS) and progression-free survival (PFS). A lesion-by-lesion analysis was performed for correlation analysis between maximum standardised uptake value (SUVmax), mean standardised uptake value (SUVmean) and mean apparent diffusion coefficient (ADC). RESULTS: Fifty patients were included in the study and divided into three groups: Hodgkin's lymphoma (HL), n=12; aggressive non-Hodgkin's lymphoma (NHL), n=29 (including 20 patients with diffuse large B-cell lymphoma, DLBCL); and indolent NHL, n=9. Indolent NHL showed significantly lower mean ADC values than the other two lymphoma groups (p=0.013). Aggressive NHL had a higher SUVmax than HL. The OS analysis of all patients showed a relationship (p=0.006) between increased mean ADC and longer OS. A model with both SUVmean and mean ADC, strengthened the possibility to predict PFS; however, a separate analysis of the DLBCL patients showed that none of the quantitative parameters could predict OS or PFS. CONCLUSION: ADC can discriminate between indolent and aggressive NHL. This finding can be useful in assessing possible transformation from indolent to aggressive NHL. ADC, ADC/SUV, and SUV cannot predict OS/PFS independent of lymphoma subtype.

Late-life obesity is associated with smaller global and regional gray matter volumes: a voxel-based morphometric study.

OBJECTIVE: Obesity adversely affects frontal lobe brain structure and function. Here we sought to show that people who are obese versus those who are of normal weight over a 5-year period have differential global and regional brain volumes. DESIGN: Using voxel-based morphometry, contrasts were done between those who were recorded as being either obese or of normal weight over two time points in the 5 years prior to the brain scan. In a post-hoc preliminary analysis, we compared scores for obese and normal weight people who completed the trail-making task. SUBJECTS: A total of 292 subjects were examined following exclusions (for example, owing to dementia, stroke and cortical infarcts) from the Prospective Investigation of the Vasculature in Uppsala Seniors cohort with a body mass index of normal weight (<25 kg m(-2)) or obese (30 kg m(-2)). RESULTS: People who were obese had significantly smaller total brain volumes and specifically, significantly reduced total gray matter (GM) volume (GMV) (with no difference in white matter or cerebrospinal fluid). Initial exploratory whole brain uncorrected analysis revealed that people who were obese had significantly smaller GMV in the bilateral supplementary motor area, bilateral dorsolateral prefrontal cortex (DLPFC), left inferior frontal gyrus and left postcentral gyrus. Secondary more stringent corrected analyses revealed a surviving cluster of GMV difference in the left DLPFC. Finally, post-hoc contrasts of scores on the trail-making task, which is linked to DLPFC function, revealed that obese people were significantly slower than those of normal weight. CONCLUSION: These findings suggest that in comparison with normal weight, people who are obese have smaller GMV, particularly in the left DLPFC. Our results may provide evidence for a potential working memory mechanism for the cognitive suppression of appetite that may lower the risk of developing obesity in later life.

Improved geometric accuracy of whole body diffusion-weighted imaging at 1.5T and 3T using reverse polarity gradients.

Whole body diffusion-weighted imaging (WB-DWI) is increasingly used in oncological applications, but suffers from misalignments due to susceptibility-induced geometric distortion. As such, DWI and structural images acquired in the same scan session are not geometrically aligned, leading to difficulties in e.g. lesion detection and segmentation. In this work we assess the performance of the reverse polarity gradient (RPG) method for correction of WB-DWI geometric distortion. Multi-station DWI and structural magnetic resonance imaging (MRI) data of healthy controls were acquired at 1.5T (n = 20) and 3T (n = 20). DWI data was distortion corrected using the RPG method based on b = 0 s/mm2 (b0) and b = 50 s/mm2 (b50) DWI acquisitions. Mutual information  (MI) between low b-value DWI and structural data increased with distortion correction (P < 0.05), while improvements in region of interest (ROI) based similarity metrics, comparing the position of incidental findings on DWI and structural data, were location dependent. Small numerical differences between non-corrected and distortion corrected apparent diffusion coefficient (ADC) values were measured. Visually, the distortion correction improved spine alignment at station borders, but introduced registration-based artefacts mainly for the spleen and kidneys. Overall, the RPG distortion correction gave an improved geometric accuracy for WB-DWI data acquired at 1.5T and 3T. The b0- and b50-based distortion corrections had a very similar performance.

Validation of automated whole-body analysis of metabolic and morphological parameters from an integrated FDG-PET/MRI acquisition.

Automated quantification of tissue morphology and tracer uptake in PET/MR images could streamline the analysis compared to traditional manual methods. To validate a single atlas image segmentation approach for automated assessment of tissue volume, fat content (FF) and glucose uptake (GU) from whole-body [18F]FDG-PET/MR images. Twelve subjects underwent whole-body [18F]FDG-PET/MRI during hyperinsulinemic-euglycemic clamp. Automated analysis of tissue volumes, FF and GU were achieved using image registration to a single atlas image with reference segmentations of 18 volume of interests (VOIs). Manual segmentations by an experienced radiologist were used as reference. Quantification accuracy was assessed with Dice scores, group comparisons and correlations. VOI Dice scores ranged from 0.93 to 0.32. Muscles, brain, VAT and liver showed the highest scores. Pancreas, large and small intestines demonstrated lower segmentation accuracy and poor correlations. Estimated tissue volumes differed significantly in 8 cases. Tissue FFs were often slightly but significantly overestimated. Satisfactory agreements were observed in most tissue GUs. Automated tissue identification and characterization using a single atlas segmentation performs well compared to manual segmentation in most tissues and will be valuable in future studies. In certain tissues, alternative quantification methods or improvements to the current approach is needed.

A 6-month randomized, double-blind, placebo-controlled trial of weekly exenatide in adolescents with obesity.

BACKGROUND: Pharmacological treatment options for adolescents with obesity are very limited. Glucagon-like-peptide-1 (GLP-1) receptor agonist could be a treatment option for adolescent obesity. OBJECTIVE: To investigate the effect of exenatide extended release on body mass index (BMI)-SDS as primary outcome, and glucose metabolism, cardiometabolic risk factors, liver steatosis, and other BMI metrics as secondary outcomes, and its safety and tolerability in adolescents with obesity. METHODS: Six-month, randomized, double-blinded, parallel, placebo-controlled clinical trial in patients (n = 44, 10-18 years, females n = 22) with BMI-SDS > 2.0 or age-adapted-BMI > 30 kg/m2 according to WHO were included. Patients received lifestyle intervention and were randomized to exenatide extended release 2 mg (n = 22) or placebo (n = 22) subcutaneous injections given once weekly. Oral glucose tolerance tests (OGTT) were conducted at the beginning and end of the intervention. RESULTS: Exenatide reduced (P < .05) BMI-SDS (-0.09; -0.18, 0.00), % BMI 95th percentile (-2.9%; -5.4, -0.3), weight (-3 kg; -5.8, -0.1), waist circumference (-3.2 cm; -5.8, -0.7), subcutaneous adipose tissue (-552 cm3 ; -989, -114), 2-hour-glucose during OGTT (-15.3 mg/dL; -27.5, -3.1), total cholesterol (11.6 mg/dL; -21.7, -1.5), and BMI (-0.83 kg/m2 ; -1.68, 0.01) without significant change in liver fat content (-1.36; -3.12, 0.4; P = .06) in comparison to placebo. Safety and tolerability profiles were comparable to placebo with the exception of mild adverse events being more frequent in exenatide-treated patients. CONCLUSIONS: Treatment of adolescents with severe obesity with extended-release exenatide is generally well tolerated and leads to a modest reduction in BMI metrics and improvement in glucose tolerance and cholesterol. The study indicates that the treatment provides additional beneficial effects beyond BMI reduction for the patient group.

Lipid mobilization following Roux-en-Y gastric bypass examined by magnetic resonance imaging and spectroscopy.

BACKGROUND: Recent developments of magnetic resonance imaging (MRI) and spectroscopy have made it possible to quantify lipid deposited in different tissues. To what extent an improvement of glucose tolerance shortly after Roux-en-Y gastric bypass surgery (RYGBP) is reflected in lipid levels in liver and skeletal muscle, markers of insulin resistance, has not been clarified. METHODS: Whole-body MRI and MR spectroscopy (MRS) of liver and muscle and measurements of biochemical markers of glucose and lipid metabolism were performed at baseline and 1, 6, and 12 months following surgery in seven morbidly obese women. Volumes of adipose tissue depots and liver and muscle lipids were assessed from the MRI/MRS data. RESULTS: At 1 month postoperatively, body mass index and visceral and subcutaneous adipose tissues were reduced by 9%, 26%, and 10%, respectively, whereas no reductions in intrahepatocellular or skeletal intramyocellular lipid concentrations were found. Free fatty acid and beta-hydroxybutyrate levels were elevated two- and sixfold, respectively; glucose and insulin levels were lowered, indicating increased insulin sensitivity. Further weight loss up to 1 year was associated with reductions in all investigated lipid depots investigated, with the exception of the intramyocellular compartment. CONCLUSION: RYGBP causes rapid lipid mobilization from visceral and subcutaneous adipose depots and enhanced free fatty acid flux to the liver. An exceptional disconnection between liver fat and insulin sensitivity occurs in the early dynamic phase after surgery. However, in the late phase, the energy restriction imposed by the surgical procedure also reduces the liver lipids, but not the intramyocellular lipids.

The prevalence and quantification of atherosclerosis in an elderly population assessed by whole-body magnetic resonance angiography.

OBJECTIVE: The principal aim of the present study was to explore the feasibility of using whole-body magnetic resonance angiography to assess atherosclerosis in different vascular territories in a cohort of elderly. METHODS AND RESULTS: Three hundred six 70-year-old subjects (145 women, 161 men) recruited from a population-based cohort study (Prospective Investigation of the Vasculature in Uppsala Seniors, ie, the PIVUS study) underwent 1.5-T whole-body magnetic resonance angiography with gadodiamide. The arteries were divided into 26 segments. In total, 7956 vessel segments were evaluated with 7900 segments (99.3%) possible to evaluate. Of these, 7186 segments (91%) were normal. Luminal narrowing of > or = 50% was observed in 9 (1.5%) of the renal arteries, 12 (1.8%) of the carotid arteries, in 31 segments (1.1%) of the pelvic/upper leg territories, and in 136 segments (6.2%) of territories in the lower leg. Approximately one-third of the sample had no vascular abnormalities, one-third had stenoses of < 50%, and the remainder had stenoses > or = 50% or occlusions. Six subjects (2%) had aortic aneurysms. In subjects without evident vascular disease, 26% had significant vascular abnormalities. CONCLUSIONS: Whole-body magnetic resonance angiography performed with a clinical scanner can be used for quantifying atherosclerosis in different vascular territories in a single examination in an elderly population.

Ankle brachial index <0.9 underestimates the prevalence of peripheral artery occlusive disease assessed with whole-body magnetic resonance angiography in the elderly.

BACKGROUND: Whole-body magnetic resonance angiography (WBMRA) permits noninvasive vascular assessment, which can be utilized in epidemiological studies. PURPOSE: To assess the relation between a low ankle brachial index (ABI) and high-grade stenoses in the pelvic and leg arteries in the elderly. MATERIAL AND METHODS: WBMRA was performed in a population sample of 306 subjects aged 70 years. The arteries below the aortic bifurcation were graded after the most severe stenosis according to one of three grades: 0-49% stenosis, 50-99% stenosis, or occlusion. ABI was calculated for each side. RESULTS: There were assessable WBMRA and ABI examinations in 268 (right side), 265 (left side), and 258 cases (both sides). At least one > or =50% stenosis was found in 19% (right side), 23% (left side), and 28% (on at least one side) of the cases. The corresponding prevalences for ABI <0.9 were 4.5%, 4.2%, and 6.6%. An ABI cut-off value of 0.9 resulted in a sensitivity, specificity, and positive and negative predictive value of 20%, 99%, 83%, and 84% on the right side, and 15%, 99%, 82%, and 80% on the left side, respectively, for the presence of a > or =50% stenosis in the pelvic or leg arteries. CONCLUSION: An ABI <0.9 underestimates the prevalence of peripheral arterial occlusive disease in the general elderly population.

Quantitative renal cortical perfusion in human subjects with magnetic resonance imaging using iron-oxide nanoparticles: influence of T1 shortening.

BACKGROUND: Using conventional contrast agents, the technique of quantitative perfusion by observing the transport of a bolus with magnetic resonance imaging (MRI) is limited to the brain due to extravascular leakage. PURPOSE: To perform quantitative perfusion measurements in humans with an intravascular contrast agent, and to estimate the influence of the T1 relaxivity of the contrast agent on the first-pass response. MATERIAL AND METHODS: Renal cortical perfusion was measured quantitatively in six patients with unilateral renal artery stenosis using a rapid gradient double-echo sequence in combination with an intravenous bolus injection of NC100150 Injection, an intravascular contrast agent based on iron-oxide nanoparticles. The influence of T1 relaxivity was measured by comparing perfusion results based on single- and double-echo data. RESULTS: The mean values of cortical blood flow, cortical blood volume, and mean transit time in the normal kidneys were measured to 339+/-60 ml/min/100 g, 41+/-8 ml/100 g, and 7.3+/-1.0 s, respectively, based on double-echo data. The corresponding results based on single-echo data, which are not compensated for the T1 relaxivity, were 254+/-47 ml/min/100 g, 27+/-3 ml/100 g, and 6+/-1.2 s, respectively. CONCLUSION: The use of a double-echo sequence enabled elimination of confounding T1 effects and consequent systematic underestimation of the perfusion.

Positron emission tomography studies in patients with locally advanced and/or metastatic breast cancer: a method for early therapy evaluation?

PURPOSE: To investigate if sequential positron emission tomographic (PET) scans with the glucose analog 18F-2-fluoro-2-deoxy-D-glucose (18FDG) and/or L-methyl-11C-methionine (11C-methionine) in patients with breast cancer could provide early information on the efficacy of polychemotherapy. PATIENTS AND METHODS: Sixteen patients with breast cancer (11 with locally advanced tumors, three with recurrent disease in the contralateral breast, two of them with distant and regional metastases, and two with distant metastases) underwent a baseline and two follow-up PET scans after the first and third/fourth polychemotherapy course. Tumor response was determined clinically/radiographically after three/four polychemotherapy courses. RESULTS: Five patients were investigated with 18FDG, seven with both 11C-methionine and 18FDG, and four with only 11C-methionine before polychemotherapy. 11C-methionine presented a more distinct visualization of primary/contralateral breast cancers in five of seven patients when compared with 18FDG. Twelve of 16 patients demonstrated a response using conventional methods after the third/fourth course of polychemotherapy. Eight of these 12 clinical responders had a significant decrease in tracer uptake at the first PET scan performed 6 to 13 days after the first polychemotherapy course, and these reductions were further augmented after the third/fourth course and corresponded to the conventional therapy evaluation (clinical examination, computed tomography [CT], ultrasonography, and mammography). CONCLUSION: Our data indicate that PET may be of clinical value in predicting response to chemotherapy in patients with locally advanced breast cancer and/or metastatic disease earlier than any other method used.

Positron emission tomography with 5-hydroxytryprophan in neuroendocrine tumors.

PURPOSE: Carcinoid tumors, especially those of midgut origin, produce serotonin via the precursors tryptophan and 5-hydroxytryptophan (5-HTP). We have evaluated the usefulness of positron emission tomography (PET) with carbon-11-labeled 5-HTP in the diagnosis and treatment follow-up evaluation of patients with neuroendocrine tumors. PATIENTS AND METHODS: PET using 11C-labeled 5-HTP was compared with computed tomography (CT) in 18 patients (14 midgut, one foregut, one hindgut carcinoid, and two endocrine pancreatic tumors [EPT]). In addition, 10 of 18 patients were monitored with PET examinations during treatment. RESULTS: All 18 patients, including two with normal urinary 5-hydroxyindole acetic acid (U-5-HIAA), had increased uptake of 11C-labeled 5-HTP in tumorous tissue as compared with normal tissue. Liver metastases, as well as lymph node, pleural, and skeletal metastases, showed enhanced 5-HTP uptake and PET could detect more lesions than CT in 10 patients and equal numbers in the others. Tumor visibility was better for PET than for CT due to the high and selective uptake of 5-HTP with a high tumor-to-background ratio. Binding studies indicated an irreversible trapping of 5-HTP in the tumors. Linear regression analyses showed a clear correlation (r = .907) between changes in U-5-HIAA and changes in the transport rate constant for 5-HTP during treatment. CONCLUSION: PET with 11C-labeled 5-HTP demonstrated high uptake in neuroendocrine gastrointestinal tumors and thereby allowed improved visualization compared with CT. The in vivo data on regional tumor metabolism, as expressed in 11C-5-HTP uptake and transport rate, provided additional information over conventional radiologic techniques. The close correlation between the changes in 11C-5-HTP transport rate and U-HIAA during medical treatment indicates the potential of 11C-5-HTP-PET as a means to monitor therapy.

NMR-based metabolic profiling in healthy individuals overfed different types of fat: links to changes in liver fat accumulation and lean tissue mass.

BACKGROUND: Overeating different dietary fatty acids influence the amount of liver fat stored during weight gain, however, the mechanisms responsible are unclear. We aimed to identify non-lipid metabolites that may differentiate between saturated (SFA) and polyunsaturated fatty acid (PUFA) overfeeding using a non-targeted metabolomic approach. We also investigated the possible relationships between plasma metabolites and body fat accumulation. METHODS: In a randomized study (LIPOGAIN study), n=39 healthy individuals were overfed with muffins containing SFA or PUFA. Plasma samples were precipitated with cold acetonitrile and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Pattern recognition techniques were used to overview the data, identify variables contributing to group classification and to correlate metabolites with fat accumulation. RESULTS: We previously reported that SFA causes a greater accumulation of liver fat, visceral fat and total body fat, whereas lean tissue levels increases less compared with PUFA, despite comparable weight gain. In this study, lactate and acetate were identified as important contributors to group classification between SFA and PUFA (P<0.05). Furthermore, the fat depots (total body fat, visceral adipose tissue and liver fat) and lean tissue correlated (P(corr)>0.5) all with two or more metabolites (for example, branched amino acids, alanine, acetate and lactate). The metabolite composition differed in a manner that may indicate higher insulin sensitivity after a diet with PUFA compared with SFA, but this needs to be confirmed in future studies. CONCLUSION: A non-lipid metabolic profiling approach only identified a few metabolites that differentiated between SFA and PUFA overfeeding. Whether these metabolite changes are involved in depot-specific fat storage and increased lean tissue mass during overeating needs further investigation.

Octreotide and interferon alfa: a new combination for the treatment of malignant carcinoid tumours.

24 patients with malignant carcinoid tumours received octreotide and interferon alfa (IFN-alpha). All the patients initially received octreotide 50-100 micrograms, twice daily. When progressive symptoms or increasing biochemical markers were observed, the daily dose was raised to a median 300 micrograms. If the initial dose proved ineffective or if no improvement was seen after escalation, IFN-alpha was added (median 9 MU subcutaneously per week). After the addition of IFN-alpha, 17 of the 22 patients (77%) with elevated urinary 5-hydroxyindoleacetic acid showed a significant (> 50%) reduction. Only 1 patient progressed and 4 had continuously stable biochemical disease. No significant reduction in tumour size was noted; in 5 patients, the tumour continued to grow despite decreasing hormone levels. 18 patients had carcinoid syndrome when IFN-alpha was added in 10 (56%) symptoms ameliorated. Thus, the addition of IFN-alpha is beneficial for patients with malignant carcinoid tumours that progress and/or who do not respond to octreotide.

Predicting malignancy grade with PET in non-Hodgkin's lymphoma.

UNLABELLED: Our goal was to determine whether PET with 11C-methionine and/or 18FDG could predict malignancy grade in non-Hodgkin's lymphoma (NHL). METHODS: Twenty-three patients with high-grade, low-grade or transformed low-grade NHL were investigated. Standardized uptake values (SUV), transport rate and mass influx values were calculated both for the whole tumor [mean regions of interest, (ROI)] and for the tumor area with the highest levels of activity, comprising four contiguous pixels within each tumor and designated as a hot spot. RESULTS: Both 11C-methionine and 18FDG detected all tumors. In addition, 18FDG discriminated between high- and low-grade NHL, whereas 11C-methionine did not. With 18FDG, three transformed low-grade NHLs behaved in an intermediate manner. All quantitative uptake values correlated well with each other for both tracers, except for the mean ROI SUV and transport rate of 11C-methionine. Quantifications of mean ROI uptake and hot spots were strongly correlated. CONCLUSION: The results of this study together with previous findings from other studies indicate that 18FDG but not 11C-methionine can predict malignancy grade in NHL. Further studies with a larger series of patients are needed.

Pharmacokinetics and experimental PET imaging of a bromine-76-labeled monoclonal anti-CEA antibody.

UNLABELLED: Bromine-76 is potentially useful as a radiolabel for monoclonal antibodies (MAbs) in PET imaging. The purpose of the present study was to evaluate the 76Br-labeled anticarcinoembryonic antigen (-CEA) MAb 38S1 as a tumor imaging agent in an experimental tumor model and to study the pharmacokinetics of 76Br-38S1 in comparison with 125I-38S1. METHODS: Nude rats carrying human colon carcinoma xenografts were co-injected with directly labeled 76Br-38S1 and 125I-38S1. Biodistribution of labeled 38S1 was monitored for 4 days after administration, in the case of 76Br activity, including PET imaging. In addition, catabolism of radiolabeled MAbs was analyzed by gel filtration chromatography of blood plasma and homogenized tissues. RESULTS: Tumor sites could be readily identified by PET imaging from 46 hr after administration of 76Br-38S1 and onwards. The concentration of 76Br activity in tumors, blood and most normal tissues was higher than the corresponding 125I concentration at all time points. This was mainly due to catabolism of radiolabeled MAb, resulting in free radiohalides, of which 76Br- was retained in contrast to the rapidly excreted 125I- ion. CONCLUSION: Bromine-76-labeled anti-CEA MAbs may be applied for experimental tumor imaging with PET.