FDG PET/CT in staging of advanced epithelial ovarian cancer: frequency of supradiaphragmatic lymph node metastasis challenges the traditional pattern of disease spread.

OBJECTIVE: Epithelial ovarian cancer (EOC) spreads intra-abdominally and to the retroperitoneal lymph nodes. A greater number of distant metastases are revealed by (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) compared to conventional imaging methods. We aimed to investigate the presence and anatomic distribution of supradiaphragmatic lymph node metastasis (LNM) detected with pretreatment FDG PET/CT. METHODS: Thirty women with advanced stage (IIC-IV) EOC were scanned with whole body contrast-enhanced FDG PET/CT prior to surgery/neoadjuvant chemotherapy. We performed PET/CT analysis qualitatively and quantitatively. Additionally, contrast-enhanced CT was analyzed blinded to PET/CT scan. Intra-abdominal dissemination was verified by surgery and histopathology. Metabolically active lymph nodes were biopsied when possible. The clinical characteristics of patients with and without supradiaphragmatic LNM were compared. RESULTS: In 20/30 patients (67%) FDG PET/CT detected supradiaphragmatic LNM in one or more locations, whereas conventional CT found LNM in 10 patients (33%). Fourteen patients had parasternal, 14 cardiophrenic, 8 other mediastinal, 6 axillar, and 1 subclavian LNM. Microscopy of all four biopsied lymph nodes (three axillar and one subclavian) confirmed metastatic dissemination. The patients with supradiaphragmatic LNM had significantly more ascites (p<0.01), higher CA 125 levels, and more frequent subdiaphragmal carcinomatosis (p<0.03) compared to patients without supradiaphragmatic LNM in preoperative FDG PET/CT. CONCLUSIONS: A significant number of patients with advanced EOC showed supradiaphragmatic LNM in pre-treatment PET/CT. Our findings suggest that the route of EOC cells from the peritoneal cavity to the lymphatic system permeates the diaphragm mainly to the cardiophrenic and continues to parasternal lymph nodes.

Diet intervention reduces uptake of αvß3 integrin-targeted PET tracer 18F-galacto-RGD in mouse atherosclerotic plaques.

BACKGROUND: Expression of α(v)ß(3) integrin has been proposed as a marker for atherosclerotic lesion inflammation. We studied whether diet intervention reduces uptake of α(v)ß(3) integrin-targeted positron emission tomography tracer (18)F-galacto-RGD in mouse atherosclerotic plaques. METHODS AND RESULTS: Hypercholesterolemic LDLR(-/-) ApoB(100/100) mice on high-fat diet for 4 months were randomized to further 3 months on high-fat diet (high-fat group, n = 8) or regular mouse chow (intervention group, n = 7). Intima-media ratio describing plaque burden was comparable between intervention and high-fat groups (2.0 ± 0.5 vs 2.3 ± 0.8, P = .5). Uptake of (18)F-galacto-RGD in the aorta was lower in the intervention than high-fat group (%ID/g 0.16 vs 0.23, P < .01). Autoradiography showed 35% lower uptake of (18)F-galacto-RGD in the atherosclerotic plaques in the intervention than high-fat group (P = .007). Uptake of (18)F-galacto-RGD in plaques correlated with uptake of (3)H-deoxyglucose and nuclear density, which was lower in the intervention than high-fat group (P = .01). Flow cytometry demonstrated macrophages expressing α(v) and ß(3) integrins in the aorta. CONCLUSIONS: Uptake of (18)F-galacto-RGD in mouse atherosclerotic lesions was reduced by lipid-lowering diet intervention. Expression of α(v)ß(3) integrin is a potential target for evaluation of therapy response in atherosclerosis.

Visual assessment of [(11)C]PIB PET in patients with cognitive impairment.

PURPOSE: The aim of this study was to evaluate the visual assessment of positron emission tomography images of N-[methyl-11C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB) in a patient population with mild to moderate memory impairment or dementia. METHODS: We compared the visual ratings of two readers using kappa statistics and correlated the results of visual and quantitative region of interest (ROI) analyses. The one reader had good experience in evaluating PIB images and the other had little previous experience. The sensitivity and specificity of the visual assessment was determined using quantitative data from 18 healthy controls previously examined: [11C]PIB uptake was considered as abnormal if it was more than 2 SD above the mean of the healthy subjects. RESULTS: The evaluation of visual classification as "normal" or "abnormal" showed good interobserver agreement (kappa = 0.90). There was a clear correlation between visual and quantitative analysis (r = 0.47-0.79, p < 0.001). The most difficult visually assessed brain area was the putamen (kappa = 0.11; correlation with quantitative analysis: reader A r = 0.22; reader B r = 0.60). CONCLUSION: Our study shows that visual evaluation of [(11)C]PIB images conforms with quantitative analyses also in a clinical patient population supporting the feasibility of visual evaluation in clinical settings.

Myocardial perfusion quantitation with 15O-labelled water PET: high reproducibility of the new cardiac analysis software (Carimas).

PURPOSE: Carimas (Cardiac Image Analysis System) is a new software package developed at the Turku PET Centre for the quantitation of PET studies of the heart with a broad range of tracers. The goal of this study was to assess the reproducibility of results the package provides for myocardial perfusion (MP) quantitation using (15)O-labelled water. METHODS: Four observers with various levels of experience in nuclear medicine independently analysed 20 MP studies (10 rest flow: "rest", 10 adenosine-induced hyperaemia: "stress"). Each study was analysed twice. The linear mixed model for repeated measures was fitted to the data to calculate intraclass correlation coefficients (ICC), differences between the repeats (the intraobserver differences) and differences between the observers (the interobserver differences). Also, Pearson correlation coefficients (r) were calculated and Bland-Altman plots were drawn. The reproducibility of MP was assessed on global, regional and segmental levels. Thereafter, this analysis was applied in 48 consecutive clinical patients with suspected coronary heart disease (CHD). RESULTS: For the experienced observer the Pearson r for all segments was 0.974 at rest and 0.978 at stress (p < 0.0001), and the repeatability coefficients were 0.145 ml/g per min (15.5% of the average) and 0.389 ml/g per min (14.9%), correspondingly. The ICC reflected very good overall reproducibility. The intraobserver and interobserver differences were small, and the difference between the most and the least experienced observers at stress was 8.5% for the global MP. The clinical accuracy of the perfusion in the detection of CHD was excellent (positive predictive value 91% and negative predictive value 88%) against invasive angiography. CONCLUSION: The results demonstrate high reproducibility of myocardial perfusion quantitation with (15)O-labelled water PET using Carimas. The results support the feasibility of robust analysis and good clinical accuracy.

C-11 acetate has excellent reproducibility for quantification of myocardial oxidative metabolism.

AIMS: C-11 acetate PET imaging allows quantification of myocardial oxidative metabolism. We sought to assess the reproducibility of such analysis with the Carimas software. METHODS AND RESULTS: The myocardial oxygen consumption rate was assessed via a kmono index--the clearance rate constant of a mono-exponential function fitted to a C-11 acetate clearance curve. Two observers of different experience levels--a novice and an expert--analysed 53 C-11 acetate PET studies--each study twice. These results were compared using Bland-Altman (BA) plots with the global kmono-s obtained earlier with a validated reference method. We also assessed intra- and interobserver reproducibility on global, regional, and segmental [17-segment model (AHA)] levels--a linear mixed model for the repeated measures was fitted to our data--using intraclass correlation coefficients (ICCs) and differences between repeats and the observers. Carimas kmono values were lower than the reference--by 10.7% in the novice and by 9.6% in the expert, and were in substantial agreement with it--R(2) values were 0.944 and 0.943 correspondingly; the coefficients of repeatability--1.96 SD of biases in BA plots--were 11.2% in both the observers. The intra- and interobserver ICCs were high on global and regional levels--above 0.99 in the novice and 0.96 in the expert. The intra- and interobserver differences were low on global and regional levels, the most pronounced being the left anterior descending artery (LAD) interobserver difference of 2.2%. CONCLUSION: The study showed extremely good reproducibility-both intra- and interobserver-for C-11 acetate PET analysis of myocardial oxidative metabolism.

Comparison of five parathyroid scintigraphic protocols.

Objectives. We compared five parathyroid scintigraphy protocols in patients with primary (pHPT) and secondary hyperparathyroidism (sHPT) and studied the interobserver agreement. The dual-tracer method ((99m)Tc-sestamibi/(123)I) was used with three acquisition techniques (parallel-hole planar, pinhole planar, and SPECT/CT). The single-tracer method ((99m)Tc-sestamibi) was used with two acquisition techniques (double-phase parallel-hole planar, and SPECT/CT). Thus five protocols were used, resulting in five sets of images. Materials and Methods. Image sets of 51 patients were retrospectively graded by four experienced nuclear medicine physicians. The final study group consisted of 24 patients (21 pHPT, 3 sHPT) who had been operated upon. Surgical and histopathologic findings were used as the standard of comparison. Results. Thirty abnormal parathyroid glands were found in 24 patients. The sensitivities of the dual-tracer method (76.7-80.0%) were similar (P = 1.0). The sensitivities of the single-tracer method (13.3-31.6%) were similar (P = 0.625). All differences in sensitivity between these two methods were statistically significant (P < 0.012). The interobserver agreement was good. Conclusion. This study indicates that any dual-tracer protocol with (99m)Tc-sestamibi and (123)I is superior for enlarged parathyroid gland localization when compared with single-tracer protocols using (99m)Tc-sestamibi alone. The parathyroid scintigraphy was found to be independent of the reporter.

Planar scintigraphy with 123I/99mTc-sestamibi, 99mTc-sestamibi SPECT/CT, 11C-methionine PET/CT, or selective venous sampling before reoperation of primary hyperparathyroidism?

UNLABELLED: All patients with primary hyperparathyroidism should undergo localization studies before reoperation, but it is not known which method is most accurate. The purpose of this prospective study was to compare the performance of planar scintigraphy with (123)I/(99m)Tc-sestamibi, (99m)Tc-sestamibi SPECT (SPECT/CT), (11)C-methionine PET/CT, and selective venous sampling (SVS) in persistent primary hyperparathyroidism. METHODS: Twenty-one patients referred for reoperation of persistent hyperparathyroidism were included and investigated with (123)I/(99m)Tc-sestamibi, SPECT/CT (n = 19), (11)C-methionine PET/CT, and SVS (n = 18) before reoperation. All patients had been operated on 1-2 times previously because of hyperparathyroidism. The results of the localization studies were compared with operative findings, histology, and biochemical cure. RESULTS: Eighteen (86%) of 21 patients were biochemically cured. Nineteen parathyroid glands (9 adenomas, 1 atypical adenoma, and 9 hyperplastic glands) were removed from 17 patients, and 1 patient who was biochemically cured had an unclear histology result. The accuracy for localizing a pathologic parathyroid gland to the correct side of the neck was 59% (95% confidence interval [CI], 36%-79%) for (123)I/(99m)Tc-sestamibi, 19% (95% CI, 5%-42%) for SPECT/CT, 65% (95% CI, 43%-84%) for (11)C-methionine PET/CT, and 40% (95% CI, 19%-65%) for SVS (P < 0.01 for (123)I/(99m)Tc-sestamibi vs. SPECT/CT). The corresponding accuracy for the correct quadrant or more specific site was 48% (95% CI, 27%-69%) for (123)I/(99m)Tc-sestamibi, 14% (95% CI, 3%-36%) for SPECT/CT, 61% (95% CI, 39%-80%) for (11)C-methionine PET/CT, and 25% (95% CI, 9%-49%) for SVS (P < 0.02 for (123)I/(99m)Tc-sestamibi vs. SPECT/CT). In the 3 patients not cured, preoperative (123)I/(99m)Tc-sestamibi and SPECT/CT remained negative, SVS was false predictive in all, and (11)C-methionine PET/CT in 1. (11)C-methionine PET/CT accurately revealed the pathologic gland in 4 of 8 (50%) patients with a negative (123)I/(99m)Tc-sestamibi scan result, all of whom were biochemically cured after reoperation. CONCLUSION: Planar scintigraphy with (123)I/(99m)Tc-sestamibi performs well in complicated primary hyperparathyroidism and is recommended as first-line imaging before reoperation. (11)C-methionine PET/CT provides valuable additional information if (123)I/(99m)Tc-sestamibi scan results remain negative. (99m)Tc-sestamibi SPECT/CT and SVS provide no additional information, compared with the combined results of (123)I/(99m)Tc-sestamibi and (11)C-methionine PET/CT imaging.

Measurement of brown adipose tissue mass using a novel dual-echo magnetic resonance imaging approach: a validation study.

OBJECTIVE: The aim of this study was to evaluate and validate magnetic resonance imaging (MRI) for the visualization and quantification of brown adipose tissue (BAT) in vivo in a rat model. We hypothesized that, based on differences in tissue water and lipid content, MRI could reliably differentiate between BAT and white adipose tissue (WAT) and could therefore be a possible alternative for (18)F-Fluorodeoxyglucose Positron Emission Tomography ((18)FDG-PET), the current gold standard for non-invasive BAT quantification. MATERIALS/METHODS: Eleven rats were studied using both (18)FDG-PET/CT and MRI (1.5 T). A dual echo (in-and-out-of-phase) sequence was used, both with and without spectral presaturation inversion recovery (SPIR) fat suppression (DUAL-SPIR) to visualize BAT, after which all BAT was surgically excised. The BAT volume measurements obtained via (18)FDG-PET/CT and DUAL-SPIR MR were quantitatively compared with the histological findings. All study protocols were reviewed and approved by the local ethics committee. RESULTS: The BAT mass measurements that were obtained using DUAL-SPIR MR subtraction images correlated better with the histological findings (P=0.017, R=0.89) than did the measurements obtained using (18)FDG-PET/CT (P=0.78, R=0.15), regardless of the BAT metabolic activation state. Additionally, the basic feasibility of the DUAL-SPIR method was demonstrated in three human pilot subjects. CONCLUSIONS: This study demonstrates the potential for MRI to reliably detect and quantify BAT in vivo. MRI can provide information beyond that provided by (18)FDG-PET imaging, and its ability to detect BAT is independent of its metabolic activation state. Additionally, MRI is a low-cost alternative that does not require radiation.

Complementary roles of 18F-DOPA PET/CT and 18F-FDG PET/CT in medullary thyroid cancer.

UNLABELLED: Serum calcitonin and carcinoembryonic antigen (CEA) are markers of recurrent or persistent disease in medullary thyroid cancer (MTC). However, conventional imaging often fails to localize metastatic disease. Our aim was to compare fluorine-labeled dihydroxyphenylalanine ((18)F-DOPA) and (18)F-FDG PET/CT with multidetector CT (MDCT) and MRI in recurrent or persistent MTC. METHODS: Nineteen MTC patients with increased calcitonin or CEA on follow-up (mean ± SD, 93 ± 91 mo; range, 4-300 mo) after primary therapy were prospectively imaged with 4 techniques: (18)F-DOPA PET/CT, (18)F-FDG PET/CT, MDCT, and MRI. Images were analyzed for pathologic lesions, which were surgically removed when possible. The correlation between the detection rate for each method and the calcitonin and CEA concentrations and histopathologic findings was investigated. RESULTS: On the basis of histology and follow-up, one or more imaging methods accurately localized metastatic disease in 12 (63%) of 19 patients. The corresponding figures for (18)F-DOPA PET/CT, (18)F-FDG PET/CT, MDCT, and MRI were 11 (58%) of 19, 10 (53%) of 19, 9 (47%) of 19, and 10 (59%) of 17, respectively. Calcitonin and CEA correlated with (18)F-DOPA PET/CT (P = 0.0007 and P = 0.0263, respectively) and (18)F-FDG PET/CT findings (both P < 0.0001). In patients with an unstable calcitonin doubling time (n = 8), (18)F-DOPA and (18)F-FDG PET/CT were equally sensitive. In contrast, for patients with an unstable CEA doubling time (n = 4), (18)F-FDG PET/CT was more accurate. CONCLUSION: For most MTC patients with occult disease, (18)F-DOPA PET/CT accurately detects metastases. In patients with an unstable calcitonin level, (18)F-DOPA PET/CT and (18)F-FDG PET/CT are complementary. For patients with an unstable CEA doubling time, (18)F-FDG PET/CT may be more feasible. MRI is sensitive but has the highest rate of false-positive results.

Does initial breastfeeding lead to lower blood cholesterol in adult life? A quantitative review of the evidence.

BACKGROUND: Earlier studies have suggested that infant feeding may program long-term changes in cholesterol metabolism. OBJECTIVE: We aimed to examine whether breastfeeding is associated with lower blood cholesterol concentrations in adulthood. DESIGN: The study consisted of a systematic review of published observational studies relating initial infant feeding status to blood cholesterol concentrations in adulthood (ie, aged >16 y). Data were available from 17 studies (17 498 subjects; 12 890 breastfed, 4608 formula-fed). Mean differences in total cholesterol concentrations (breastfed minus formula-fed) were pooled by using fixed-effect models. Effects of adjustment (for age at outcome, socioeconomic position, body mass index, and smoking status) and exclusion (of nonexclusive breast feeders) were examined. RESULTS: Mean total blood cholesterol was lower (P = 0.037) among those ever breastfed than among those fed formula milk (mean difference: -0.04 mmol/L; 95% CI: -0.08, 0.00 mmol/L). The difference in cholesterol between infant feeding groups was larger (P = 0.005) and more consistent in 7 studies that analyzed "exclusive" feeding patterns (-0.15 mmol/L; -0.23, -0.06 mmol/L) than in 10 studies that analyzed nonexclusive feeding patterns (-0.01 mmol/L; -0.06, 0.03 mmol/L). Adjustment for potential confounders including socioeconomic position, body mass index, and smoking status in adult life had minimal effect on these estimates. CONCLUSIONS: Initial breastfeeding (particularly when exclusive) may be associated with lower blood cholesterol concentrations in later life. Moves to reduce the cholesterol content of formula feeds below those of breast milk should be treated with caution.

Does initial breastfeeding lead to lower blood cholesterol in adult life? A quantitative review of the evidence

Objective: We aimed to examine whether breastfeeding is associated with lower blood cholesterol concentrations in adulthood...