RT Journal Article SR Electronic T1 First-in-Human Assessment of the Novel PDE2A PET Radiotracer 18F-PF-05270430 JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1388 OP 1395 DO 10.2967/jnumed.115.166850 VO 57 IS 9 A1 Mika Naganawa A1 Rikki N. Waterhouse A1 Nabeel Nabulsi A1 Shu-Fei Lin A1 David Labaree A1 Jim Ropchan A1 Sanela Tarabar A1 Nicholas DeMartinis A1 Adam Ogden A1 Anindita Banerjee A1 Yiyun Huang A1 Richard E. Carson YR 2016 UL http://jnm.snmjournals.org/content/57/9/1388.abstract AB This was a first-in-human study of the novel phosphodiesterase-2A (PDE2A) PET ligand 18F-PF-05270430. The primary goals were to determine the appropriate tracer kinetic model to quantify brain uptake and to examine the within-subject test–retest variability. Methods: In advance of human studies, radiation dosimetry was determined in nonhuman primates. Six healthy male subjects participated in a test–retest protocol with dynamic scans and metabolite-corrected input functions. Nine brain regions of interest were studied, including the striatum, white matter, neocortical regions, and cerebellum. Multiple modeling methods were applied to calculate volume of distribution (VT) and binding potentials relative to the nondisplaceable tracer in tissue (BPND), concentration of tracer in plasma (BPP), and free tracer in tissue (BPF). The cerebellum was selected as a reference region to calculate binding potentials. Results: The dosimetry study provided an effective dose of less than 0.30 mSv/MBq, with the gallbladder as the critical organ; the human target dose was 185 MBq. There were no adverse events or clinically detectable pharmacologic effects reported. Tracer uptake was highest in the striatum, followed by neocortical regions and white matter, and lowest in the cerebellum. Regional time–activity curves were well fit by multilinear analysis-1, and a 70-min scan duration was sufficient to quantify VT and the binding potentials. BPND, with mean values ranging from 0.3 to 0.8, showed the best intrasubject and intersubject variability and reliability. Test–retest variability in the whole brain (excluding the cerebellum) of VT, BPND, and BPP were 8%, 16%, and 17%, respectively. Conclusion: 18F-PF-05270430 shows promise as a PDE2A PET ligand, albeit with low binding potential values.