Quantification of ¹⁸F-JNJ42259152, a novel phosphodiesterase 10A (PDE 10A) PET-tracer: Kinetic modeling and test-retest

Objectives Phosphodiesterase 10A (PDE10A) plays a central role in striatal signaling and is implicated in several neuropsychiatric disorders. We performed initial brain kinetic modeling of the novel PDE10A tracer ¹⁸F-JNJ42259152 and studied test-retest reproducibility in healthy volunteers.

Methods 9 healthy volunteers (4 M/5 F; 42-69y) were scanned dynamically up to 135 minutes after bolus injection of 172.5±10.3MBq of ¹⁸F-JNJ42259152. Three (1 M/2 F) underwent retest scanning with a mean interscan interval of 37d. Input functions and parent fractions were determined using arterial sampling. VOIs in the caudate (CN), putamen (PT), ventral striatum (VS), substantia nigra (SN) and cerebellum (CBL) were delineated using the individual’s MRI. One (1T) and two tissue (2T) models were evaluated. Distribution volumes (V_T) were compared with binding potential (BP) by a simplified reference tissue model (SRTM) using CBL as reference. 90 (SRTM90) and 60 min (SRTM60) scan time intervals were considered. V_T and BP test-retest variability was assessed.

Results The average intact tracer half life in blood was 90 min. 1T V_T values for CN, PT, VS, SN and CBL were 1.55±0.51, 0.91±0.29, 0.63±0.20, 0.40±0.13 and 0.31±0.07, respectively. 2T provided similar V_T values. SRMT BP values for CN, PT, VS and SN were 2.80±0.46, 1.40±0.43, 0.76±0.39 and 0.19±0.14, respectively. SRMT90 and SRMT60 values showed very low bias. Good correlations were found for CN, PT and VS between 1T V_T and BP SRMT, BP SRMT90 and BP SRTM60 (r = 0.84, 0.85 and 0.83 respectively). Test-retest variability was 11-16% for 1T V_T, 13-15% for BP SRMT, 10-14% for BP SRMT90 and 8-12% for BP SRTM60.

Conclusions Kinetic modeling of ¹⁸F-JNJ42259152 shows that PDE10A activity can be reliably quantified non-invasively using a simplified reference tissue model with the cerebellum as reference, with clinically acceptable acquisition times