TY - JOUR T1 - Quantification of <sup>18</sup>F-JNJ-42259152, a Novel Phosphodiesterase 10A PET Tracer: Kinetic Modeling and Test–Retest Study in Human Brain JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1285 LP - 1293 DO - 10.2967/jnumed.112.118679 VL - 54 IS - 8 AU - Koen Van Laere AU - Rawaha U. Ahmad AU - Hendra Hudyana AU - Kristof Dubois AU - Mark E. Schmidt AU - Sofie Celen AU - Guy Bormans AU - Michel Koole Y1 - 2013/08/01 UR - http://jnm.snmjournals.org/content/54/8/1285.abstract N2 - Phosphodiesterase 10A (PDE10A) plays a central role in striatal signaling and is implicated in several neuropsychiatric disorders, such as movement disorders and schizophrenia. We performed initial brain kinetic modeling of the novel PDE10A tracer 18F-JNJ-42259152 (2-[[4-[1-(2-18F-fluoroethyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]phenoxy]methyl]-3,5-dimethyl-pyridine) and studied test–retest reproducibility in healthy volunteers. Methods: Twelve healthy volunteers (5 men, 7 women; age range, 42–77 y) were scanned dynamically up to 135 min after bolus injection of 172.5 ± 10.3 MBq of 18F-JNJ42259152. Four volunteers (2 men, 2 women) underwent retest scanning, with a mean interscan interval of 37 d. Input functions and tracer parent fractions were determined using arterial sampling and high-performance liquid chromatography analysis. Volumes of interest for the putamen, caudate nucleus, ventral striatum, substantia nigra, thalamus, frontal cortex, and cerebellum were delineated using individual volumetric T1 MR imaging scans. One-tissue (1T) and 2-tissue (2T) models were evaluated to calculate total distribution volume (VT). Simplified models were also tested to calculate binding potential (BPND), including the simplified reference tissue model (SRTM) and multilinear reference tissue model, using the frontal cortex as the optimal reference tissue. The stability of VT and BPND was assessed down to a 60-min scan time. Results: The average intact tracer half-life in blood was 90 min. The 2T model VT values for the putamen, caudate nucleus, ventral striatum, substantia nigra, thalamus, frontal cortex, and cerebellum were 1.54 ± 0.37, 0.90 ± 0.24, 0.64 ± 0.18, 0.42 ± 0.09, 0.35 ± 0.09, 0.30 ± 0.07, and 0.36 ± 0.12, respectively. The 1T model provided significantly lower VT values, which were well correlated to the 2T VT. SRTM BPND values referenced to the frontal cortex were 3.45 ± 0.43, 1.78 ± 0.35, 1.10 ± 0.31, and 0.44 ± 0.09 for the respective target regions putamen, caudate nucleus, ventral striatum, and substantia nigra, with similar values for the multilinear reference tissue model. Good correlations were found for the target regions putamen, caudate nucleus, ventral striatum, and substantia nigra between the 2T-compartment model BPND and the SRTM BPND (r = 0.57, 0.82, 0.70, and 0.64, respectively). SRTM BPND using a 90- and 60-min acquisition interval showed low bias. Test–retest variability was 5%–19% for 2T VT and 5%–12% for BPND SRTM. Conclusion: Kinetic modeling of 18F-JNJ-42259152 shows that PDE10A activity can be reliably quantified and simplified using a reference tissue model with the frontal cortex as reference and a 60-min acquisition period. ER -