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Purpose The plasma membrane P-glycoprotein (Pgp) is an efflux transporter involved in multidrug resistance and in the onset of neurodegenerative disease. Its function and most mechanisms of action are still under investigation. We developed a C-11-labeled 2-arylethylphenylamine-([11C]AEPH) derivative for positron emission tomography (PET), as a novel probe to better understand the activity and the function of Pgp in vivo.

In this work, we propose and test a new approach for non-linear kinetic parameters' estimation from dynamic PET data. A technique is discussed, to derive an analytical closed-form expression of the compartmental model used for kinetic parameters' evaluation, using an auxiliary parameter set, with the aim of reducing the computational burden and speeding up the fitting of these complex mathematical expressions to noisy TACs. Two alternative algorithms based on numeric calculations are considered and compared to the new proposal. We perform a simulation study aimed at (i) assessing agreement between the proposed method and other conventional ways of implementing compartmental model fitting, and (ii) quantifying the reduction in computational time required for convergence. It results in a speed-up factor of ∼120 when compared to a fully numeric version, or ∼38, with respect to a more conventional implementation, while converging to very similar values for the estimated model parameters. The proposed method is also tested on dynamic 3D PET clinical data of four control subjects. The results obtained supported those of the simulation study, and provided input and promising perspectives for the application of the proposed technique in clinical practice.

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.

We propose and test a novel approach for direct parametric image reconstruction of dynamic PET data. We present a theoretical description of the problem of PET direct parametric maps estimation as an inference problem, from a probabilistic point of view, and we derive a simple iterative algorithm, based on the Iterated Conditional Mode (ICM) framework, which exploits the simplicity of a two-step optimization and the efficiency of an analytic method for estimating kinetic parameters from a nonlinear compartmental model. The resulting method is general enough to be flexible to an arbitrary choice of the kinetic model, and unlike many other solutions, it is capable to deal with nonlinear compartmental models without the need for linearization. We tested its performance on a two-tissue compartment model, including an analytical solution to the kinetic parameters evaluation, based on an auxiliary parameter set, with the aim of reducing computation errors and approximations. The new method is tested on simulated and clinical data. Simulation analysis led to the conclusion that the proposed algorithm gives a good estimation of the kinetic parameters in any noise condition. Furthermore, the application of the proposed method to clinical data gave promising results for further studies.

The plasma membrane P-glycoprotein (Pgp) is an efflux transporter involved in multidrug resistance and in the onset of neurodegenerative disease. Its function and most mechanisms of action are still under investigation. We developed a C-11-labeled 2-arylethylphenylamine-([The synthetic procedure and the quality control of the selected lead compound, [In vivo dynamic imaging was consistent with the results of ex vivo extraction on explanted organs. An adequate stability for in vivo studies, as well as a high activity of [The suitable pharmacokinetics and the specificity tested in the pre-treated animals have indicated the potentiality of this AEPH derivative to act as Pgp ligand, providing new opportunities for further studies on expression and function of this important efflux transporter in the fields of neurology and oncology.

Aim The aim of this study was to evaluate the possible impact of stress-induced left ventricular (LV) diastolic dysfunction at cadmium–zinc–telluride (CZT) imaging, on the detection of significant coronary artery disease (CAD). Methods and results Four hundred and twenty-five consecutive patients underwent myocardial perfusion imaging at rest and after stress with a low-dose CZT protocol and the evaluation of coronary anatomy by invasive or computed coronary angiography. The summed difference score (SDS) was calculated in every patient. Left ventricular ejection fraction and peak filling rate (PFR) at baseline and after stress were derived from gated CZT images and the ‘% stress-to-rest’ PFR difference, as an indicator of stress-induced diastolic dysfunction, determined. In the study population, the mean SDS was 5 ± 4, while mean stress PFR and rest PFR were 2.5 ± 0.8 end-diastolic volumes (EDV)/s and 2.5 ± 0.7 EDV/s, respectively. There was a strict correlation between the presence and extent of CAD and both myocardial SDS and ‘% stress-to-rest’ PFR ( P < 0.001 for both). Interestingly, while myocardial SDS and ‘% stress-to-rest’ PFR were significantly correlated ( P < 0.001), they resulted independent predictors of the presence of significant CAD ( P < 0.001 and P < 0.032, respectively). Of note, at receiving operating characteristic analysis, a ‘% stress-to-rest’ PFR ≤3 showed 71% sensitivity in unmasking the presence of significant coronary luminal narrowings. Conclusion The present study shows that the assessment of stress-induced diastolic dysfunction with an ultrafast scintigraphic protocol can improve the accuracy in detection of significant ischaemic heart disease.