BRIEF REPORT Test–Retest Reproducibility of [C]-(+)-Propyl- Hexahydro-Naphtho-Oxazin Positron Emission Tomography Using the Bolus plus Constant Infusion Paradigm

We examined the reproducibility of using the constant infusion paradigm for equilibrium measurement of D2/3 receptors using [ C](+)-propyl-hexahydro-naphtho-oxazin (PHNO) positron emission tomography (PET). Six subjects were scanned with a bolus plus constant infusion (Kbol 5 80 minutes) of [ C]-(+)-PHNO. Binding potential (BPND) was computed using the equilibrium approach and compared to a simplified reference tissue model (SRTM). The rate of change in the concentration-activity curve from 60 to 90 minutes was 25 6 13%/h in the caudate, putamen, substantia nigra, thalamus, and cerebellum but was 15 6 15%/h in the ventral striatum and pallidum. Test–retest variability was lower in striatal compared to extrastriatal regions (4 6 8% vs 28 6 22%, respectively) using the equilibrium approach, with comparable results with SRTM. The equilibrium ratio and SRTM yielded reliable BPND estimates (intraclass correlation coefficient 5 0.88 and 0.82, respectively). These studies support the reproducibility of the bolus plus constant infusion paradigm with [C]-(+)-PHNO PET. [11C] -(+)-propyl-hexahydro-naphtho-oxazin(PHNO) is a high-affinity D2/3 agonist radiotracer used for positron emission tomography (PET) brain imaging. Unlike other D2/3 radiotracers that have higher affinity for D2 over D3 receptors (eg, [ C]raclopride, [F]fallypride, [C]FLB, [C]NPA, and [C]MNPA), the affinity of [C]-(+)-PHNO is < 40 times higher for D3 than for D2 receptors. 5–7 As an agonist, [C]-(+)-PHNO binds to receptors in the high-affinity state, whereas antagonists bind to both highand low-affinity receptors. The high-affinity D2/3 receptors are thought to be more functionally relevant than low-affinity receptors and more susceptible to extracellular changes in endogenous dopamine, which binds primarily to high-affinity D2/3 receptors. Thus, [C]-(+)-PHNO may provide a more sensitive measure of functionally relevant D2/3 receptors than antagonist radiotracers. A preliminary study using a bolus administration of [C]-(+)-PHNO demonstrated that the radiotracer has good test–retest reliability, with variability between scans less than 12.5% across regions. The bolus plus constant infusion method provides several advantages over the bolus-only method of radiotracer administration. Therefore, in the current study, we examined the feasibility and reproducibility of a constant infusion paradigm for examining D2/3 receptor availability with [C]-(+)-PHNO PET. Materials and Methods