Differentiation of suprasellar meningiomas from non-functioning pituitary macroadenomas by 18F-FDG and 13N-Ammonia PET/CT.

BACKGROUND: Differentiation of suprasellar meningiomas (SSMs) from non-functioning pituitary macroadenomas (NFPMAs) is useful for clinical management. We investigated the utility of 13N-ammonia combined with 18F-FDG positron emission tomography (PET)/computed tomography (CT) in distinguishing SSMs from NFPMAs retrospectively. METHODS: Fourteen NFPMA patients and eleven SSM patients with histopathologic diagnosis were included in this study. Every patient underwent both 18F-FDG and 13N-ammonia PET/CT scans. The tumor to gray matter (T/G) ratios were calculated for the evaluation of tumor uptake. RESULTS: The uptake of 18F-FDG was higher in NFPMAs than SSMs, whereas the uptake of 13N-ammonia was obviously lower in NFPMAs than SSMs. The differences of 18F-FDG and 13N-ammonia uptake between the two groups were significant respectively (0.92[0.46] vs 0.59[0.29], P < 0.05, 18F-FDG; 1.58 ± 0.56 vs 2.80 ± 1.45, P < 0.05, 13N-ammonia). Tumor classification demonstrated a high overall accuracy of 96.0% for differential diagnosis. When the two traces were combined, only 1 SSM was misclassified into the NFPMA group. CONCLUSION: SSMs and NFPMAs have different metabolic characteristics on 18F-FDG and 13N-ammonia PET images. The combination of these two tracers can effectively distinguish SSMs from NFPMAs.

Diagnostic accuracy of 13N-ammonia PET, 11C-methionine PET and 18F-fluorodeoxyglucose PET: a comparative study in patients with suspected cerebral glioma.

BACKGROUND: The treatment of patients with glioma depended on the nature of the lesion and on histological grade of the tumor. Positron emission tomography (PET) using 13N-ammonia (NH3), 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) have been used to assess brain tumors. Our aim was to compare their diagnostic accuracies in patients with suspected cerebral glioma. METHODS: Ninety patients with suspicion of glioma based on previous CT/MRI, who underwent NH3 PET, MET PET and FDG PET, were prospectively enrolled in the study. The reference standard was established by histology or clinical and radiological follow-up. Images were interpreted by visual evaluation and semi-quantitative analysis using the lesion-to-normal white matter uptake ratio (L/WM ratio). RESULTS: Finally, 30 high-grade gliomas (HGG), 27 low-grade gliomas (LGG), 10 non-glioma tumors and 23 non-neoplastic lesions (NNL) were diagnosed. On visual evaluation, sensitivity and specificity for differentiating tumors from NNL were 62.7% (42/67) and 95.7% (22/23) for NH3 PET, 94.0% (63/67) and 56.5% (13/23) for MET PET, and 35.8% (24/67) and 65.2% (15/23) for FDG PET. On semi-quantitative analysis, brain tumors showed significantly higher L/WM ratios than NNL both in NH3 and MET PET (both P < 0.001). The sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic (ROC) analysis, respectively, were 64.2, 100% and 0.819 for NH3; and 89.6, 69.6% and 0.840 for MET. Besides, the L/WM ratios of NH3, MET and FDG PET in HGG all significantly higher than that in LGG (all P < 0.001). The predicted (by ROC) accuracy of the tracers (AUC shown in parentheses) were 86.0% (0.896) for NH3, 87.7% (0.928) for MET and 93.0% (0.964) for FDG. While no significant differences in the AUC were seen between them. CONCLUSION: NH3 PET has remarkably high specificity for the differentiation of brain tumors from NNL, but low sensitivity for the detection of LGG. MET PET was found to be highly useful for detection of brain tumors. However, like FDG, high MET uptake is frequently observed in some NNL. NH3, MET and FDG PET all appears to be valuable for evaluating the histological grade of gliomas.

Myocardial Microvascular Dysfunction in Rheumatoid ArthritisQuantitation by 13N-Ammonia Positron Emission Tomography/Computed Tomography.

BACKGROUND: The goal of this study was to assess the prevalence of myocardial microvascular dysfunction in rheumatoid arthritis (RA) patients without clinical cardiovascular disease and its association with RA characteristics and measures of cardiac structure and function. METHODS: Participants with RA underwent rest and vasodilator stress N-13 ammonia positron emission tomography and echocardiography. Global myocardial blood flow was quantified at rest and during peak hyperemia. Myocardial flow reserve (MFR) was calculated as peak stress myocardial blood flow/rest myocardial blood flow. A small number of asymptomatic and symptomatic non-RA controls were also evaluated. RESULTS: In RA patients, mean±SD MFR was 2.9±0.8, with 29% having reduced MFR (<2.5). Male sex and higher interleukin-6 were significantly associated with lower MFR, while the use of tumor necrosis factor inhibitors was associated with higher MFR. Lower MFR was associated with higher left ventricle mass index and higher left ventricle volumes but not with ejection fraction or diastolic dysfunction. RA and symptomatic controls had comparable MFR (mean±SD: 2.9±0.8 versus 2.55±0.6; P=0.48). In contrast, MFR was higher in the asymptomatic controls (mean±SD: 3.25±0.7) although not statistically different. CONCLUSIONS: Reduced MFR was observed in a third of RA patients without clinical cardiovascular disease and was associated with a measure of inflammation and with higher left ventricle mass and volumes. MFR in RA patients was similar to controls referred for clinical scans (symptomatic controls). Whether reduced MFR contributes to the increased risk for heart failure in RA remains unknown.

Myocardial bridging of the left anterior descending coronary artery is associated with reduced myocardial perfusion reserve: a 13N-ammonia PET study.

Myocardial Bridging (MB) refers to the band of myocardium that abnormally overlies a segment of a coronary artery. This paper quantitatively evaluates the influence of MB of the left anterior descending artery (LAD) on myocardial perfusion of the entire left ventricle. We studied 131 consecutive patients who underwent hybrid rest/stress 13N-ammonia positron emission tomography (PET) and coronary computed tomography angiography (CCTA) due to suspected myocardial ischemia. Patients with previous myocardial infarction and/or significant coronary artery disease (≥ 50% stenosis) were excluded. Myocardial perfusion measurements were compared between patients with and without LAD-MB. Additionally, we evaluated the relationship between anatomical characteristics (length and depth) of LAD-MB and myocardial perfusion measurements. 17 (13%) patients presented a single LAD-MB. Global myocardial perfusion reserve (MPR) was lower in patients with LAD-MB than in patients without LAD-MB (1.9 ± 0.5 vs. 2.3 ± 0.6, p < 0.01). Global stress myocardial blood flow (MBF) was similar in patients with and without LAD-MB (2.2 ± 0.4 vs. 2.3 ± 0.7 ml/g/min, p = 0.40). Global rest MBF was higher in patients with LAD-MB than in patients without LAD-MB (1.2 ± 0.3 vs. 1.0 ± 0.2 ml/g/min, p < 0.01). Global rest MBF, stress MBF, and MPR quantifications were similar in patients with superficial and deep LAD-MB (all p = NS). We did not find any correlation between length and global rest MBF, stress MBF nor MPR (r = - 0.14, p = 0.59; r = 0.44, p = 0.07; and r = 0.45, p = 0.07 respectively). Quantitative myocardial perfusion suggests that LAD-MB may be related to impaired perfusion reserve, an indicator of microvascular dysfunction. Anatomical characteristics of LAD-MB were not related to changes in myocardial perfusion.

13N-ammonia combined with 18F-FDG could discriminate between necrotic high-grade gliomas and brain abscess.

PURPOSE: Accurate prediction of brain abscess is beneficial for timely management. In this study, we investigated the utility of 13N-ammonia and its combination with 18F-FDG in differentiating brain abscess from necrotic high-grade gliomas. PATIENTS AND METHODS: Thirteen patients with ring-like enhancement high-grade gliomas and 11 patients with brain abscess were recruited in our study. All of them underwent both 18F-FDG and 13N-ammonia PET imaging. Lesion uptake was evaluated by lesion to normal gray matter ratio (L/N). Histopathology diagnosis was obtained for all the patients after PET imaging. RESULTS: The L/N values of 18F-FDG were not significantly different between brain abscess and necrotic high-grade gliomas (P = 0.35). The uptake of 13N-ammonia in gliomas was higher than that in abscess lesions (L/N: 1.38 ± 0.31 vs 0.84 ± 0.18, P < 0.001). The receiver operating characteristic curve analysis determined the optimal L/N cutoff value (13N-ammonia) of 1.0 with the area under the curve of 0.94 and the overall accuracy of 87.5%. Discriminant analysis demonstrated that the combination of 18F-FDG and 13N-ammonia could distinguish the 2 clinical entities with higher accuracy of 95%, and only 1 necrotic glioma lesion was misclassified into the abscess group. CONCLUSIONS: 13N-ammonia is effective in distinguishing brain abscess from necrotic high-grade gliomas, and its combination with 18F-FDG could further elevate the diagnostic accuracy.

Accuracy of cardiac PET imaging using post-injection transmission scan.

UNLABELLED: The purpose of this study was to investigate the accuracy of cardiac PET with post-injection transmission scans. METHODS: We performed a phantom study using 18F solution as well as 13N-ammonia PET study of ten patients. The average activities of no myocardial defect phantom model were estimated, and myocardial defect sizes of 12 phantom models were measured by pre- and post-injection transmission methods at various 18F activities. In 13N-ammonia PET at rest and during adenosine triphosphate (ATP) stress studies, measured defect sizes were compared between both methods. RESULTS: The ratios of average activity estimated by both methods (post/pre value) were almost 1.00 at each 18F activity and segment. Measured defect sizes by both methods showed an excellent correlation with true defect sizes (r = 0.98, p < 0.01 for pre vs. true value: r = 0.98, p < 0.01 for post vs. true value). The mean absolute errors of measurements were minimal up to 3.5% LV, and were similar between both methods. In 13N-ammonia PET, measured defect sizes by both methods also showed a good correlation (r = 0.97, p < 0.01). CONCLUSION: The results indicate that cardiac PET imaging with post-injection transmission scan provides information on myocardial tracer activity as well as myocardial defect size as does conventional pre-injection transmission method.

Recovery of (15)n in the body, urine, and gas phase of piglets infused intravenously with (15)n L-alanine from 12-72 hours of age.

Previous studies of nitrogen metabolism provided evidence suggesting that nitrogen excretory product(s) not measured by standard methods of analysis escape detection. To determine whether (15)N could be recovered quantitatively in the body, urine, or expired gas, newborn piglets (n = 16; 1.47 +/- 0.27 kg) were infused intravenously with (15)N L-alanine from 12 to 72 h of age at a rate providing 25% of the piglets' resting energy expenditure and a (15)N abundance of 2.3 (n = 4), 2.8 (n = 10), or 3.3 (n = 2) atom percent. To investigate the possibility of gaseous nitrogen excretion, 4 piglets infused with (15)N L-alanine were housed in a closed circuit respiration system initially flushed with an 80% argon:20% O(2) mixture. The gas composition of the system was monitored at 12-h intervals throughout the experiment. Mean total recovery of (15)N was 93.3 +/- 2.8% and was significantly different from 100% (P < 0.001). To determine whether (15)N recovery was altered by metabolism, 2 piglets (1.34 +/- 0.13 kg) were killed 6 min after a bolus i.v. infusion of (15)N L-alanine (97.96 +/- 1.13 atom percent). Mean recovery of (15)N in the bodies of these piglets was 101.5 +/- 1.6% and was not different from 100%. No change in chamber gas (28)N(2) (P = 0.0969) or (29)N(2) (P = 0.08565) over 72 h was evident. The inability to recover 6.7 +/- 2.8% of infused (15)N suggests that a nitrogen-containing excretory product or metabolite may be escaping detection, but the discrepancy cannot be explained by gaseous nitrogen ((28)N(2), (29)N(2), or (30)N(2)) excretion.

Advantages of short-lived positron-emitting radioisotopes for intracoronary radiation therapy with liquid-filled balloons to prevent restenosis.

UNLABELLED: Balloon catheters filled with liquid radioisotopes provide excellent dose homogeneity for intracoronary radiation therapy but are associated with risk for rupture or leakage. We hypothesized that the safety of liquid-filled balloons may be improved once positron emitters with half-lives below 2 h are used instead of the high-energy beta-emitters 166Ho, 186Re, or 188Re, all of which have a longer half-life of at least 17 h. METHODS: To support this concept, the suitability of 18F (half-life, 109.8 min), 68Ga (half-life, 67.6 min), 11C (half-life, 20.4 min), 13N (half-life, 9.97 min), and 15O (half-life, 2.04 min) for intracoronary radiation therapy was evaluated. Potential tissue penetration of positron radiation was assessed in a series of phantom experiments using Gafchromic film. Antiproliferative efficacy of positrons emitted by 68Ga was investigated in vitro using cultured bovine aortic smooth muscle cells (BASMCs), and was compared with gamma-radiation emitted by 137Cs. To characterize the remaining risk, we estimated radiotoxicity after accidental intravascular balloon rupture on the basis of tabulated isotope-specific doses (ICRP 53) and compared these values with 188Re. RESULTS: Half-dose depth of tissue penetration measured in phantom experiments was 0.29 mm for 18F, 0.42 mm for 11C, 0.54 mm for 13N, 0.79 mm for 15O, and 0.9 mm for 68Ga. Irradiation of cultured BASMCs with positron radiation (68Ga) induced dose-dependent inhibition of proliferation with complete proliferative arrest at doses exceeding 6 Gy. ED(50) and ED(80) were 2.5 +/- 0.4 Gy (mean +/- SD) and 4.4 +/- 0.8 Gy, respectively. Antiproliferative efficacy was equal to that of the 662-keV gamma-radiation emitted by 137Cs (ED(50), 3.8 +/- 0.2 Gy; ED(80), 8.0 +/- 0.3 Gy). Estimates made for patient whole-body and organ doses were generally below 50 mSv/1.85 GBq for all investigated positron emitters. The same dose estimates for 188Re were 6-20 fold higher. CONCLUSION: Among the studied radioisotopes, 68Ga is the most attractive source for liquid-filled balloons because of its convenient half-life, sufficient positron energy (2.92 MeV), documented antiproliferative efficacy, and uncomplicated availability from a radioisotope generator. The safety profile for 68Ga is significantly better than that of 188Re, which suggests this radioisotope should be evaluated further in preclinical studies.

Imaging of the human heart after administration of L-(N-13)glutamate.

In normal volunteers and cancer patients, studies using L-(N-13)glutamate as an imaging agent showed localization of N-13 activity in the heart. Other organs that were well visualized include the liver, pancreas, and salivary glands. In ten subjects the average myocardial uptake after intravenous injection of labeled glutamate was (5.7 +/- 0.39)% (s.e.m.) of injected dose, as determined by a quantitative scanning system. The concentration of N-13 activity in the human heart could not be predicted from previous studies involving myocardial uptake in dogs and rodents after administration of L-(N-13)glutamate.