Quantification of aromatase binding in the female human brain using [11 C]cetrozole positron emission tomography.

Aromatase, the enzyme that in the brain converts testosterone and androstenedione to estradiol and estrone, respectively, is a putative key factor in psychoneuroendocrinology. In vivo assessment of aromatase was performed to evaluate tracer kinetic models and optimal scan duration, for quantitative analysis of the aromatase positron emission tomography (PET) ligand [11 C]cetrozole. Anatomical magnetic resonance and 90-min dynamic [11 C]cetrozole PET-CT scans were performed on healthy women. Volume of interest (VOI)-based analyses with a plasma-input function were performed using the single-tissue and two-tissue (2TCM) reversible compartment models and plasma-input Logan analysis. Additionally, the simplified reference tissue model (SRTM), Logan reference tissue model (LRTM), and standardized uptake volume ratio model, with cerebellum as reference region, were evaluated. Parametric images were generated and regionally averaged voxel values were compared with VOI-based analyses of the reference tissue models. The optimal reference model was used for evaluation of a decreased scan duration. Differences between the plasma-input- and reference tissue-based methods and comparisons between scan durations were assessed by linear regression. The [11 C]cetrozole time-activity curves were best described by the 2TCM. SRTM nondisplaceable binding potential (BPND ), with cerebellum as reference region, can be used to estimate [11 C]cetrozole binding and generated robust and quantitatively accurate results for a reduced scan duration of 60 min. Receptor parametric mapping, a basis function implementation of SRTM, as well as LRTM, produced quantitatively accurate parametric images, showing BPND at the voxel level. As PET tracer, [11 C]cetrozole can be employed for relatively short brain scans to measure aromatase binding using a reference tissue-based approach.

In Vivo Instability of 177Lu-DOTATATE During Peptide Receptor Radionuclide Therapy.

Peptide receptor radiotherapy using 177Lu-labeled somatostatin ligand analogs is a well-established treatment for neuroendocrine tumors, with 177Lu-DOTATATE having acquired marketing authorization in Europe and the United States. The investigation of the pharmacokinetics of these radiopharmaceuticals in vivo in humans is crucial for personalized treatment management and understanding of treatment effects. Such an investigation requires input data on the in vivo stability of the radiopharmaceuticals in blood and plasma. The work presented here is devoted to the investigation of the in vivo stability of 177Lu-DOTATATE in humans affected by neuroendocrine tumors. Methods: Blood samples of 6 patients undergoing 177Lu-DOTATATE were taken at 0.5, 4, 24, and 96 h after injection. Analysis of metabolic stability was performed using high-performance liquid chromatography. Results: A fast metabolism of the radiopharmaceutical was observed, with the fraction of intact 177Lu-DOTATATE in plasma decreasing rapidly to 23% ± 5% (mean ± SD) at 24 h and 1.7% ±0. 9% at 96 h after injection. Conclusion: The in vivo stability of 177Lu-DOTATATE is much lower than previously assumed, with the major part of radioactivity in plasma consisting of 177Lu-labeled metabolites already at 24 h after injection.

Quantification of 11C-PIB kinetics in cardiac amyloidosis.

BACKGROUND: The purpose of this work was to determine the optimal tracer kinetic model of 11C-PIB and to validate the use of the simplified methods retention index (RI) and standardized uptake value (SUV) for quantification of cardiac 11C-PIB uptake in amyloidosis. METHODS AND RESULTS: Single-tissue, reversible and irreversible two-tissue models were fitted to data from seven cardiac amyloidosis patients who underwent 11C-PIB PET scans and arterial blood sampling for measurement of blood radioactivity and metabolites. The irreversible two-tissue model (2Tirr) best described cardiac 11C-PIB uptake. RI and SUV showed high correlation with the rate of irreversible binding (Ki) from the 2Tirr model (r2 =0.95 and r2 =0.94). Retrospective data from 10 amyloidosis patients and 5 healthy controls were analyzed using RI, SUV, as well as compartment modelling with a population-average metabolite correction. All measures were higher in amyloidosis patients than in healthy controls (p=.001), but with an overlap between groups for Ki. CONCLUSION: An irreversible two-tissue model best describes the 11C-PIB uptake in cardiac amyloidosis. RI and SUV correlate well with Ki from the 2Tirr model. RI and SUV discriminate better between amyloidosis patients and controls than Ki based on population-average metabolite correction.

Overeating Saturated Fat Promotes Fatty Liver and Ceramides Compared With Polyunsaturated Fat: A Randomized Trial.

CONTEXT: Saturated fatty acid (SFA) vs polyunsaturated fatty acid (PUFA) may promote nonalcoholic fatty liver disease by yet unclear mechanisms. OBJECTIVE: To investigate if overeating SFA- and PUFA-enriched diets lead to differential liver fat accumulation in overweight and obese humans. DESIGN: Double-blind randomized trial (LIPOGAIN-2). Overfeeding SFA vs PUFA for 8 weeks, followed by 4 weeks of caloric restriction. SETTING: General community. PARTICIPANTS: Men and women who are overweight or have obesity (n = 61). INTERVENTION: Muffins, high in either palm (SFA) or sunflower oil (PUFA), were added to the habitual diet. MAIN OUTCOME MEASURES: Lean tissue mass (not reported here). Secondary and exploratory outcomes included liver and ectopic fat depots. RESULTS: By design, body weight gain was similar in SFA (2.31 ± 1.38 kg) and PUFA (2.01 ± 1.90 kg) groups, P = 0.50. SFA markedly induced liver fat content (50% relative increase) along with liver enzymes and atherogenic serum lipids. In contrast, despite similar weight gain, PUFA did not increase liver fat or liver enzymes or cause any adverse effects on blood lipids. SFA had no differential effect on the accumulation of visceral fat, pancreas fat, or total body fat compared with PUFA. SFA consistently increased, whereas PUFA reduced circulating ceramides, changes that were moderately associated with liver fat changes and proposed markers of hepatic lipogenesis. The adverse metabolic effects of SFA were reversed by calorie restriction. CONCLUSIONS: SFA markedly induces liver fat and serum ceramides, whereas dietary PUFA prevents liver fat accumulation and reduces ceramides and hyperlipidemia during excess energy intake and weight gain in overweight individuals.