A clinically important task in diabetes management is the prevention of hypo/hyperglycemic events. In this proof-of-concept paper, we assess the feasibility of approaching the problem with continuous glucose monitoring (CGM) devices. In particular, we study the possibility to predict ahead in time glucose levels by exploiting their recent history monitored every 3 min by a minimally invasive CGM system, the Glucoday, in 28 type 1 diabetic volunteers for 48 h. Simple prediction strategies, based on the description of past glucose data by either a first-order polynomial or a first-order autoregressive (AR) model, both with time-varying parameters determined by weighted least squares, are considered. Results demonstrate that, even by using these simple methods, glucose can be predicted ahead in time, e.g., with a prediction horizon of 30 min crossing of the hypoglycemic threshold can be predicted 20-25 min ahead in time, a sufficient margin to mitigate the event by sugar ingestion.

The serotonin (5-hydroxytryptamine, or 5-HT) type 1A receptor (5-HT_1AR) is implicated in the pathophysiology of numerous neuropsychiatric disorders. We have published the initial evaluation and reproducibility in vivo of [O-methyl-¹¹C]2-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)dione (¹¹C-CUMI-101), a novel 5-HT_1A agonist radiotracer, in Papio anubis. Here, we report the optimal modeling parameters of ¹¹C-CUMI-101 for human PET studies. Methods: PET scans were obtained for 7 adult human volunteers. ¹¹C-CUMI-101 was injected as an intravenous bolus, and emission data were collected for 120 min in 3-dimensional mode. We evaluated 10 different models using metabolite-corrected arterial input functions or reference region approaches and several outcome measures. Results: When using binding potential (BP_F = B_avail/K_D [total available receptor concentration divided by the equilibrium dissociation constant]) as the outcome measure, the likelihood estimation in the graphical analysis (LEGA) model performed slightly better than the other methods evaluated at full scan duration. The average test–retest percentage difference was 9.90% ± 5.60%. When using BP_ND (BP_ND = f_nd × B_avail/K_D; BP_ND equals the product of BP_F and f_nd [free fraction in the nondisplaceable compartment]), the simplified reference tissue method (SRTM) achieved the lowest percentage difference and smallest bias when compared with nondisplaceable binding potential obtained from LEGA using the metabolite-corrected plasma input function (r² = 0.99; slope = 0.92). The time–stability analysis indicates that a 120-min scan is sufficient for the stable estimation of outcome measures. Voxel results were comparable to region-of-interest–based analysis, with higher spatial resolution. Conclusion: On the basis of its measurable and stable free fraction, high affinity and selectivity, good blood–brain barrier permeability, and plasma and brain kinetics, ¹¹C-CUMI-101 is suitable for the imaging of high-affinity 5-HT_1A binding in humans.