Temporally Overlapping Dual-Tracer PET Studies

There has been increased interest in studying multiple neurotransmitter–neuroreceptor systems within the same subject. Currently, examination of two distinct neuropharmacologic measures with positron emission tomography (PET) involves performing two independent scans. This chapter proposes a dual-tracer protocol with a single overlapping PET scan and analysis using a combined compartmental model. Advantages include (1) reduction in scan time by 1.5–2 hr, (2) neuropharmacology measures would be obtained over nearly the same interval, and (3) interventional protocols involving a pair of dual-tracer scans could be performed in a single session. Simulations were performed for various combinations of three tracers: [11C]flumazenil (FMZ), [11C]dihydrotetrabenazine (DTBZ), and N-[11C]methylpiperidinylpropionate (PMP). Noisy time-activity curves were generated simulating injection separations of 10–30 min. Model parameters were estimated for both tracers simultaneously using the combined model. For FMZ/DTBZ, two parallel two-compartment configurations were used, estimating K1 and distribution volume (DV) for each ligand. For tracer pairs involving PMP, a parallel two- and three-compartment combination was used, estimating K1 and DV for FMZ or DTBZ and K1 and k3 for PMP. Parameter estimation accuracy is strongly dependent on the choice of tracers, the brain region, the parameter of interest, the injection order, and, obviously, the injection spacing. Examination of the covariance among parameters is important for interpreting model performance. Making specific conclusions that can be generalized to any tracer pair is difficult; however, the use of tracers with rapid kinetics will yield greater success. The authors conclude that dual-tracer single-scan PET is feasible and can be implemented with a number of different radiotracers.