Potential synergy between PSMA uptake and tumour blood flow for prediction of human prostate cancer aggressiveness

Background Both prostate-specific membrane antigen (PSMA) uptake and tumour blood flow (TBF) correlate with International Society of Urological Pathology (ISUP) Grade Group (GG) and hence prostate cancer (PCa) aggressiveness. The aim of the present study was to evaluate the potential synergistic benefit of combining the two physiologic parameters for separating significant PCa from insignificant findings. Methods From previous studies of [Rb-82]Rb positron emission tomography (PET) TBF in PCa, the 43 patients that underwent clinical [Ga-68]Ga-PSMA-11 PET were selected for this retrospective study. Tumours were delineated on [Ga-68]Ga-PSMA-11 PET or magnetic resonance imaging. ISUP GG was recorded from 52 lesions. Results [Ga-68]Ga-PSMA-11 maximum standardized uptake value (SUVmax) and [Rb-82]Rb SUVmax correlated moderately with ISUP GG (rho = 0.59 and rho = 0.56, both p < 0.001) and with each other (r = 0.65, p < 0.001). A combined model of [Ga-68]Ga-PSMA-11 and [Rb-82]Rb SUVmax separated ISUP GG > 2 from ISUP GG 1-2 and benign with an area-under-the-curve of 0.85, 96% sensitivity, 74% specificity, and 95% negative predictive value. The combined model performed significantly better than either tracer alone did (p < 0.001), primarily by reducing false negatives from five or six to one (p <= 0.025). Conclusion PSMA uptake and TBF provide complementary information about tumour aggressiveness. We suggest that a combined analysis of PSMA uptake and TBF could significantly improve the negative predictive value and allow non-invasive separation of significant from insignificant PCa

Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs

Background. Obesity and metabolic syndrome (MetS) are major risk factors for atherosclerotic diseases; however, a causal link remains elusive. Animal models resembling human MetS and its complications, while important, are scarce. We aimed at developing a porcine model of human MetS. Methods. Forty pigs with familial hypercholesterolemia were fed a high fat + fructose diet for 30 weeks. Metabolic assessments and subcutaneous fat biopsies were obtained at 18 and 30 weeks, and fat distribution was assessed by CT-scans. Postmortem, macrophage density, and phenotype in fat tissues were quantified along with atherosclerotic burden. Results. During the experiment, we observed a >4-fold in body weight, a significant but small increase in fasting glucose (4.1 mmol/L), insulin (3.1 mU/L), triglycerides (0.5 mmol/L), and HDL cholesterol (2.6 mmol/L). Subcutaneous fat correlated with insulin resistance, but intra-abdominal fat correlated inversely with insulin resistance and LDL cholesterol. More inflammatory macrophages were found in visceral versus subcutaneous fat, and inflammation decreased in subcutaneous fat over time. Conclusions. MetS based on human criteria was not achieved. Surprisingly, visceral fat seemed part of a healthier metabolic and inflammatory profile. These results differ from human findings, and further research is needed to understand the relationship between obesity and MetS in porcine models

Automatic extraction of forward stroke volume using dynamic PET/CT : a dual-tracer and dual-scanner validation in patients with heart valve disease.

BACKGROUND: The aim of this study was to develop and validate an automated method for extracting forward stroke volume (FSV) using indicator dilution theory directly from dynamic positron emission tomography (PET) studies for two different tracers and scanners. METHODS: 35 subjects underwent a dynamic (11)C-acetate PET scan on a Siemens Biograph TruePoint-64 PET/CT (scanner I). In addition, 10 subjects underwent both dynamic (15)O-water PET and (11)C-acetate PET scans on a GE Discovery-ST PET/CT (scanner II). The left ventricular (LV)-aortic time-activity curve (TAC) was extracted automatically from PET data using cluster analysis. The first-pass peak was isolated by automatic extrapolation of the downslope of the TAC. FSV was calculated as the injected dose divided by the product of heart rate and the area under the curve of the first-pass peak. Gold standard FSV was measured using phase-contrast cardiovascular magnetic resonance (CMR). RESULTS: FSVPET correlated highly with FSVCMR (r = 0.87, slope = 0.90 for scanner I, r = 0.87, slope = 1.65, and r = 0.85, slope = 1.69 for scanner II for (15)O-water and (11)C-acetate, respectively) although a systematic bias was observed for both scanners (p < 0.001 for all). FSV based on (11)C-acetate and (15)O-water correlated highly (r = 0.99, slope = 1.03) with no significant difference between FSV estimates (p = 0.14). CONCLUSIONS: FSV can be obtained automatically using dynamic PET/CT and cluster analysis. Results are almost identical for (11)C-acetate and (15)O-water. A scanner-dependent bias was observed, and a scanner calibration factor is required for multi-scanner studies. Generalization of the method to other tracers and scanners requires further validation

Cardiovascular Effects of Treatment With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients

BACKGROUND: Myocardial utilization of 3-hydroxybutyrate (3-OHB) is increased in patients with heart failure and reduced ejection fraction (HFrEF). However, the cardiovascular effects of increased circulating plasma-3-OHB levels in these patients are unknown. Consequently, the authors' aim was to modulate circulating 3-OHB levels in HFrEF patients and evaluate: (1) changes in cardiac output (CO); (2) a potential doseresponse relationship between 3-OHB levels and CO; (3) the impact on myocardial external energy efficiency (MEE) and oxygen consumption (MVO 2); and (4) whether the cardiovascular response differed between HFrEF patients and age-matched volunteers. METHODS: Study 1: 16 chronic HFrEF patients (left ventricular ejection fraction: 37 +/- 3%) were randomized in a crossover design to 3-hour of 3-OHB or placebo infusion. Patients were monitored invasively with a Swan-Ganz catheter and with echocardiography. Study 2: In a doseresponse study, 8 HFrEF patients were examined at increasing 3-OHB infusion rates. Study 3 to 4: 10 HFrEF patients and 10 age-matched volunteers were randomized in a crossover design to 3-hour 3-OHB or placebo infusion. MEE and MVO 2 were evaluated using 11C-acetate positron emission tomography. RESULTS: 3-OHB infusion increased circulating levels of plasma 3-OHB from 0.4 +/- 0.3 to 3.3 +/- 0.4 mM (P< 0.001). CO rose by 2.0 +/- 0.2 L/min (P< 0.001) because of an increase in stroke volume of 20 +/- 2 mL (P< 0.001) and heart rate of 7 +/- 2 beats per minute (bpm) (P< 0.001). Left ventricular ejection fraction increased 8 +/- 1% (P< 0.001) numerically. There was a dose-response relationship with a significant CO increase of 0.3 L/min already at plasma-3-OHB levels of 0.7 mM (P< 0.001). 3-OHB increased MVO 2 without altering MEE. The response to 3-OHB infusion in terms of MEE and CO did not differ between HFrEF patents and age-matched volunteers. CONCLUSIONS: 3-OHB has beneficial hemodynamic effects in HFrEF patients without impairing MEE. These beneficial effects are detectable in the physiological concentration range of circulating 3-OHB levels. The hemodynamic effects of 3-OHB were observed in both HFrEF patients and age-matched volunteers. 3-OHB may potentially constitute a novel treatment principle in HFrEF patients