In vivo quantitative assessments with [11C]T-278, a PET imaging agent for diacylglycerol kinase gamma, in nonhuman primate brain

Diacylglycerol kinase (DGK) is an enzyme catalyzing ATP-dependent conversion of diacylglycerol to phosphatidic acid. Among DGK subtypes, DGKγ is localized in the brain and plays important roles in the central nervous system, although its detailed functions remain unknown. Recently, [¹¹C]T-278 was developed as a selective positron emission tomography (PET) imaging agent for DGKγ. This study aimed to conduct the first quantitative analysis using PET with [¹¹C]T-278 in nonhuman primate brains. In rhesus monkeys, compartmental analyses showed superior goodness-of-fit in two-tissue compartment model than one-tissue compartment model. Full kinetic analysis of [¹¹C]T-278 yielded reliable estimates of the total distribution volume (V_T) values across various brain regions, showing a strong correlation (slope = 1.07, r > 0.995) with V_T value derived from Logan GA. Furthermore, time-stability analysis for V_T estimations showed small variations (< 5 %) between 70 and 90 min of scan durations across most regions of interest. This study provides the first in vivo visualization of DGKγ in monkey brain using quantitative PET analysis with [¹¹C]T-278.