Journal of Neuroscience Methods 196 (2011) 70–75 Contents lists available at ScienceDirect Journal of Neuroscience Methods journal homepage: www.elsevier.com/locate/jneumeth Assessment of IP injection of [ 18 F]fallypride for behavioral neuroimaging in rats Karmen K. Yoder ∗ , Bruce H. Mock, Qi-Huang Zheng, Brian P. McCarthy, Amanda A. Riley, Gary D. Hutchins Department of Radiology and Imaging Sciences, Indiana University School of Medicine, R2 E124, 950 W. Walnut St., Indianapolis, IN 46202, USA article info Article history: Received 5 October 2010 Received in revised form 15 December 2010 Accepted 29 December 2010 Key words: Dopamine Small animal imaging Fallypride D2 receptor Positron emission tomography Behavioral neuroimaging abstract Great progress has been made toward using small animal PET to assess neurochemical changes during behavior. [ 18 F]fallypride (FAL) is a D 2 /D 3 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. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Recently, the scope and relevance of small animal PET imag- ing were expanded by the first reports of behavioral neuroimaging with [ 18 F]FDG and [ 11 C]raclopride (Carrion et al., 2009; Patel et al., 2008; Schiffer et al., 2007, 2009). Although the [ 11 C]raclopride data documenting changes in striatal dopamine during behavior are exciting, the long half-life of [ 18 F] tracers would permit more flex- ibility in choice of behavioral paradigms. [ 18 F]Fallypride (FAL) is a high-affinity dopamine D 2 /D 3 antagonist that is used to exam- ine relative changes in striatal and extrastriatal dopamine during cognitive and pharmacological challenges in humans (Christian et al., 2006; Cropley et al., 2008; Mukherjee et al., 2005; Riccardi et al., 2006; Slifstein et al., 2010). Given that the dopamine sys- tem is implicated in multiple processes underlying psychiatric and neurological disorders, it would be valuable to use FAL PET to probe the dopamine system during behavior in animal mod- els of human disease states. In order to administer radiotracer to awake animals in a non-invasive manner (i.e., without an implanted venous catheter or tail vein injection), intraperitoneal (IP) injec- ∗ Corresponding author. Tel.: +1 317 278 9840; fax: +1 317 274 1067. E-mail address: kkyoder@iupui.edu (K.K. Yoder). tions of tracer would be required. Indeed, PET scanning after IP injection of [ 18 F]FDG in awake animals has proven useful for assess- ment of relative glucose metabolism (Carrion et al., 2009; Schiffer et al., 2007). The primary objective of this study was to determine whether IP injections of FAL would produce equivalent data to that from PET scans performed with an intravenous (IV) tail vein injection. 2. Materials and methods All procedures were carried out in accordance with National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23), and were approved by the Indiana University School of Medicine Institutional Animal Care and Use Committee. 2.1. Subjects Four male Sprague–Dawley rats (average weight over all scans: 295.9 ± 33.3 g) were scanned on the IndyPET III scanner (Rouze et al., 2004, 2005) with 3D acquisition. Three rats underwent both IP and IV protocols; one rat (Rat 5) received only an IP FAL scan (this animal died of complications from anesthesia; only 30 min of scan data were available). Scan order (IV versus IP) was counter- 0165-0270/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.jneumeth.2010.12.027