PET quantification of [(18)F]MPPF in the canine brain using blood input and reference tissue modelling

Numerous studies have shown that the serotonin(1A) (5-HT(1A)) receptor is implicated in the pathophysiology and treatment of several psychiatric and neurological disorders. Furthermore, functional imaging studies in a variety of species have demonstrated that 4-(2´-Methoxyphenyl)-1-[2´-(N-2´´-pyridinyl)-p- [(18)F]fluorobenzamidoethylpiperazine ([(18)F]MPPF) is a valid and useful PET tracer to visualize the 5HT(1A) receptor. However, to our knowledge, [(18)F]MPPF has never been demonstrated in the canine brain. The ability to image the 5HT(1A) receptor with PET in dogs could improve diagnosis and therapy in both canine and human behavioural and neuropsychiatric disorders. To examine the potential use of [(18)F]MPPF in dogs, five healthy adult laboratory beagles underwent a 60-minutes dynamic PET scan with [(18)F]MPPF while arterial blood samples were taken. For each region of interest, total distribution volume (V(T)) and corresponding binding potential (BP(ND)) were calculated using the 1-tissue compartment model (1-TC), 2-Tissue compartment model (2-TC) and Logan plot. The preferred model was chosen based on the goodness-of-fit, calculated with the Akaike information criterium (AIC). Subsequently, the BP(ND) values of the preferred compartment model were compared with the estimated BP(ND) values using three reference tissue models (RTMs): the 2-step simplified reference tissue model (SRTM2), the 2-parameter multilinear reference tissue model (MRTM2) and the Logan reference tissue model. According to the lower AIC values of the 2-TC model compared to the 1-TC in all ROIs, the 2-TC model showed a better fit. Calculating BP(ND) using reference tissue modelling demonstrated high correlation with the BP(ND) obtained by metabolite corrected plasma input 2-TC. This first-in-dog study indicates the results of a bolus injection with [(18)F]MPPF in dogs are consistent with the observations presented in the literature for other animal species and humans. Furthermore, for future experiments, compartmental modelling using invasive blood sampling could be replaced by RTMs, using the cerebellum as reference region.