Association between semiquantitative PET parameters and molecular subtypes of breast invasive ductal carcinoma.

BACKGROUND: Molecular subtypes of breast cancer have been proposed since 2012. The correlation between various baseline [18F]fluorodeoxyglucose ([18F]FDG) uptake parameters, including total lesion glycolysis (TLG), and molecular subtypes of primary breast cancer lesions in patients with invasive ductal cancer will be investigated. METHODS: Staging [18F]FDG PET/CT for breast invasive ductal carcinoma were retrospectively evaluated. Breast lesions were examined for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation index (Ki-67). Breast tumors were classified into five molecular subtypes: Luminal A, Luminal B-HER2(-), Luminal B-HER2(+), HER2(+) and Basal or Triple Negative cancers. The correlations between tumor characteristics and PET semiquantitative data of primary breast lesion (SUVmean, SUVmax, Mean tumor volume (MTV), TLG) were assessed. Specific Breast Uptake Ratio (SBUR) is used as a new quantification method of breast uptake to correct for physiological background activity. RESULTS: Fifty-eight patients were included. TLG was significantly higher in triple negative group when compared with luminal A (P<0.01). Significantly higher uptake was found in triple negative lesions when compared with luminal B-HER2(-) and luminal B-HER2(+) categories using SUVmax, SUVmean and TLG (all P<0.05). Conversely, no statistically significant difference for [18F]FDG uptake was observed between all other molecular subtypes. No value of SBUR in terms of correlation with histopathological parameters was demonstrated. CONCLUSIONS: TLG was superior to SUVmax and SUVmean in differentiating between triple negative breast cancer lesions and all other molecular subtypes. SBUR was not different statistically between various molecular subtypes.

Effect of prolonged fasting and low molecular weight heparin or warfarin therapies on 2-deoxy-2-[18F]-fluoro-D-glucose PET cardiac uptake.

BACKGROUND: Whether anticoagulants other than unfractionated heparin are able to suppress cardiac PET uptake of 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) is unknown. METHODS: One-hundred-seventy-four patients without history and clinical evidence of cardiac dysfunction and/or coronary heart disease underwent a 18F-FDG PET/CT study. All patients were studied with a >12-hours fasting and divided into 2 groups: group-1 without anticoagulant therapy (n:75); group-2 patients on low molecular weight heparin (n:60) or warfarin therapy (n:39). Cardiac 18F-FDG uptake was estimated qualitatively using a 4-point scale and semiquantitatively as total LV glycolysis (LVG) and metabolic volume (MV), drawing isocontour volume of interest (VOI) including the whole LV. RESULTS: Qualitatively, LV 18-FDG uptake was scored 0 or 1, indicating a good suppression, in 10/75 (13%) patients of group-1 and 77/99 (78%) of group-2 (p < .001). Semiquantitatively, patients of group-1 showed higher values of 18-FDG uptake than patients of group-2, assessed as LVG (802,649 ± 468,442 vs 198,989 ± 261,439, p < .0001) or MV (219 ± 77 vs 57 ± 48 cm3, p < .0001). Subanalysis for anticoagulant drugs showed similar results. CONCLUSIONS: Prolonged fasting combined to anticoagulants other than unfractionated heparin is able to minimize glucose cardiac metabolism. Our data confirm previous observation on the possibility to influence the metabolic pattern of the heart before the PET scan and broadens the spectrum of pharmacological options.

Food addiction distinguishes an overweight phenotype that can be reversed by low calorie diet.

Similarities in neural activation patterns in obese and substance-dependent subjects led to the food addiction concept, but studies exploiting this issue for obesity stratification are missing. We assessed brain activation in response to food cues using 18 F-2-fluoro-2-deoxy-glucose-PET in 36 overweight women, stratified by low or high food addiction groups according to the Yale Food Addiction Scale (YFAS). Assessments were repeated after a 3-month diet. We found greater activation in thalamus, hypothalamus, midbrain, putamen, and occipital cortex (reward), but not in prefrontal and orbitofrontal cortices (control/reward receipt) in the high-YFAS versus low-YFAS group. In high-YFAS subjects, orbitofrontal responsiveness was inversely related to YFAS severity and hunger rating, and positive associations were observed between regional brain activation and lipid intake. A 3-month diet abolished group differences in brain activation. Our data suggest that food addiction distinguishes an overweight phenotype that can be reversed by diet, opening to personalized strategies in obesity treatment.

Evaluation of ischaemia in obese patients: feasibility and accuracy of a low-dose protocol with a cadmium-zinc telluride camera.

PURPOSE: Obesity is a significant and independent risk factor for cardiovascular disease, and assessing ischaemia in obese patients is clinically important but sometimes difficult because of imaging artefacts. The aim of this study was to evaluate the feasibility and diagnostic accuracy of stress/rest imaging with a cadmium-zinc telluride (CZT) camera using a low-dose protocol in a series of consecutive obese patients referred for the evaluation of coronary artery disease. METHODS: We considered 148 consecutive obese patients (mean BMI 39 ± 7 kg/m(2)) with known or suspected coronary artery disease referred to our laboratory for stress/rest myocardial perfusion imaging. A subgroup of 103 of the 148 patients underwent invasive coronary angiography for clinical reasons. All patients underwent a single-day stress/rest low-dose ultrafast protocol. Patients were injected with (99m)Tc-tetrofosmin at a dose in the range 185-222 MBq during bicycle exercise or dipyridamole stress, and underwent the first scan with an acquisition time of 7 min starting 15 min after the end of the stress. The rest scan with an acquisition time of 6 min was started from 30 to 45 min after (99m)Tc-tetrofosmin injection at a dose in the range 370-444 MBq. Images were visually inspected, and the summed stress score (SSS) and summed rest score (SRS) were obtained. RESULTS: Image quality was graded very good or excellent in all patients. Of the 103 patients who underwent coronary angiography, 12 (12 %), 26 (25 %) and 56 (54 %) showed one-, two- and three-vessel disease, and 9 showed normal coronary vessels. In the 103 patients submitted to coronary angiography, the mean SSS and SRS were 7 ± 6 and 2 ± 3, respectively. Semiquantitative regional and global SSS was a good discriminant of coronary artery disease and the area under the overall ROC curve was 0.848 (95 % CI 0.723-0.975). CONCLUSION: In obese patients, a single-day stress/rest low-dose ultrafast protocol with a CZT camera is clinically feasible and provides high image quality.

Abnormal glucose and lipid control in non-ischemic left ventricular dysfunction.

BACKGROUND: Cardiovascular risk factors are classically associated with coronary atherosclerosis. We sought to investigate whether risk factors are also associated with left ventricular (LV) dilatation, contractile impairment and reduced myocardial blood flow (MBF) in patients with non-ischemic LV dysfunction. METHODS: We studied 81 patients (59 males, age 60 ± 9 years) with mild-to-severe LV dysfunction (mean ejection fraction 37%, range 19%-50%), no history of diabetes and normal coronary arteries. Absolute MBF was measured by positron emission tomography and (13)N-ammonia at rest and after dipyridamole (0.56 mg/kg I.V. over 4 min). RESULTS: Overt LV dysfunction (LV end-diastolic diameter >60 mm associated with LV ejection fraction <45%) was present in 42 patients (52%); severely depressed hyperemic MBF (<1.09 mL · min(-1) · g(-1)) was present in 41 patients (51%). Using multivariate logistic regression analysis, low high-density lipoprotein cholesterol (HDL-C, P < .036), newly diagnosed non-insulin-dependent diabetes or insulin-resistance (NIDD/IR, P < .019) and the use of diuretics (P = .001) were independently associated with overt LV dysfunction. Low HDL-C (P = .015) and NIDD/IR (P = .048) were also independently associated with severely depressed hyperemic MBF. CONCLUSIONS: Low HDL-C and NIDD/IR are associated with more severe LV impairment and reduced hyperemic MBF in non-ischemic LV dysfunction.

Striatal Dopamine Transporter Modulation After Rotigotine: Results From a Pilot Single-Photon Emission Computed Tomography Study in a Group of Early Stage Parkinson Disease Patients.

INTRODUCTION: Several in vitro data have reported negative interference by dopamine-agonists on the expression of dopamine transporter (DAT), whereas the majority of imaging studies have shown that neither L-dopa nor dopamine-agonists interfere with DAT availability. As yet, there are no in vivo studies on DAT expression after treatment with rotigotine. METHODS: We evaluated presynaptic nigrostriatal function in 8 patients with de novo Parkinson disease (age, 59 ± 6.2 years; male/female sex, 5/3) using 123-I- N-ω-fluoropropyl-2-ß-carbomethoxy-3-ß-(4-iodophenyl)nortropane (FP-CIT) single-photon emission computed tomography before and after 3 months of treatment with rotigotine (mean dose, 7.75 ± 1.98 mg). For data analysis, specific (left and right caudate, left and right putamen) to nonspecific (occipital cortex) binding ratios, putamen-to-caudate ratios, and asymmetry indices were calculated. RESULTS: After rotigotine, motor symptoms improved in all patients (Unified Parkinson Disease Rating Scale III mean score, 11.88 ± 2.59 vs 7.63 ± 1.92 on therapy; P = 0.0022). Striatal FP-CIT levels showed a significant improvement in every patient at the follow-up scan. Comparisons between before and after treatment in the whole group revealed a significant improvement in FP-CIT uptake in both caudate and putamen (P < 0.001 in each nucleus). Putamen-to-caudate ratio and asymmetry indices did not show any significant difference before and after treatment. DISCUSSION: Although the study population was small, we found DAT overexpression after chronic treatment with rotigotine, presumably related to its pharmacological profile. The DAT upregulation by rotigotine in an opposite direction with respect to early Parkinson disease compensatory mechanisms might reduce the risk of dyskinesia, but it could imply less motor benefit because of less stimulation by the dopamine itself on dopaminergic receptors.

Is recombinant human TSH as effective as thyroid hormone withdrawal in the detection and treatment of metastatic differentiated thyroid cancer?

Evaluation of: Van Nostr D, Khorjekav GR, O'Neil J et al. Recombinant human thyroid-stimulating hormone versus thyroid hormone withdrawal in the identification of metastasis in differentiated thyroid cancer with 131I planar whole body imaging and 124I PET. J. Nucl. Med 53(3), 359-362 (2012). In a recent article, Van Nostrand et al. compared two methods of patient preparation, that is, recombinant human thyroid-stimulating hormone and thyroid hormone withdrawal, for the detection of metastasis in patients previously treated for differentiated thyroid cancer, using both 131I whole-body imaging and 124I positron emission tomography. The major finding of this prospective study was that the number of patients and the number of foci for patient positive at 131I whole-body imaging and 124I PET performed after thyroid hormone withdrawal was significantly higher when compared with that related to patients prepared with recombinant human thyroid-stimulating hormone.

Structural abnormalities of the coronary arterial wall--in addition to luminal narrowing--affect myocardial blood flow reserve.

UNLABELLED: Multislice CT provides information on coronary luminal narrowing and on the structural abnormalities of the coronary arterial wall using densitometric analysis. We sought to investigate the effects of coronary luminal narrowing, structural abnormalities of the coronary arterial wall, and cardiovascular risk factors on regional and global myocardial blood flow (MBF) reserve. METHODS: We studied 68 patients (mean age ± SD, 61 ± 10 y; 41 men, 27 women) with an intermediate probability of coronary artery disease. We measured the severity of coronary stenoses and the fibroadipose, fibromuscular, and calcium components of the coronary arterial wall by 64-row multislice CT coronary angiography. We also measured regional and global MBF reserve by PET using (13)N-ammonia as a flow tracer at rest and after dipyridamole. RESULTS: One or more significant coronary stenoses (≥50% luminal narrowing) was present in 32 patients (47%), and nonsignificant stenoses were present in 15 patients (22%). Regional MBF reserve was significantly different in the territories perfused by normal coronary arteries, nonsignificant coronary stenoses, and significant coronary stenoses (P < 0.001). Calcium content was higher in the coronary arteries with significant or nonsignificant stenoses (0.95% ± 1.08% and 0.73% ± 0.93%, respectively) than in those without stenoses (0.11% ± 0.38%, P < 0.001). Significant coronary stenosis (P = 0.047) and calcium content (P = 0.017) were the only independent determinants of impaired regional MBF reserve using multivariate analysis. At multiple logistic regression analysis, the Framingham risk score, an index of global cardiovascular risk burden, was the only significant determinant of global MBF reserve (P = 0.028). CONCLUSION: Coronary stenoses and coronary calcium content independently affect regional MBF reserve. Framingham risk score is the only significant determinant of global MBF reserve.