Assessment of IP injection of [18F]fallypride for behavioral neuroimaging in rats

Great progress has been made toward using small animal PET to assess neurochemical changes during behavior. [18F]fallypride (FAL) is a D2/D3 antagonist that is sensitive to changes in endogenous dopamine, and, in theory, could be used to assess changes in dopamine during behavioral paradigms. Tail vein injections of tracer require restraint in awake animals, and catheter implantation is invasive and can cause logistical problems. Thus, administering tracer with IP injections (which are well-tolerated by rodents) would be preferable. The purpose of this study was to determine whether IP injection of FAL would produce striatal uptake similar to that seen with traditional IV tail vein injection protocols. Four male Sprague–Dawley rats underwent IP injection of FAL, followed by a 30-min uptake and subsequent dynamic image acquisition on the IndyPET III small animal scanner. Three of these rats also received traditional dynamic scanning with IV FAL injection via a tail vein. Two rats that received IP injection had moderate striatal uptake, with striatum/cerebellum ratios (SUVR) that were only ∼20% lower than ratios from IV scans. Two other rats had little to no uptake; SUVR values were ∼70% lower than IV SUVR. These latter two animals showed heavy bone uptake, evidence of defluorination of FAL. The results of this pilot study suggest that it may be possible to achieve striatal uptake of FAL after IP injection. However, this was not seen consistently across animals. Future studies are needed to validate, and then to optimize, the use of IP FAL for behavioral imaging protocols.

Research highlights▶ IP injection of [18F]fallypride results in measurable, but variable, striatal uptake. ▶ Drugs that prevent defluorination of [18F]fallypride should improve the striatal signal. ▶ Further characterization of IP [18F]fallypride is needed to develop this paradigm for assessing changes in in vivo dopamine during behavior.