Small Animal PET/MR Imaging

PET studies of the gastrointestinal tract were performed in male C57/BL6J mice in two experimental series. The first experimental series (age = 14 months; weight = 28–35 g), was composed of a control group (n = 5) and a treated group (n = 6), respectively unexposed or exposed for 2 months to rotenone. The second experimental series (age = 16 months; weight = 28–35 g), was composed of a control group (n = 2) and a treated group (n = 5), respectively unexposed or exposed for 4 months to rotenone. To evaluate the impact of exposure to rotenone on the cholinergic innervation of the gut, we performed in vivo PET imaging. We selected a clinically used radiotracer, (–)-[¹⁸F]Flubatine, selective of the α4β2* nicotinic acetylcholine receptor subtype to perform these experiments. The reasons to select this radiotracer were its rapid availability and its pharmacokinetic characteristics. (–)-[¹⁸F]Flubatine is not metabolized through the intestine and this is an important property, as it would otherwise dramatically increase the signal in this region interfering with the analysis. The animals received an intravenous injection of (–)-[¹⁸F]Flubatine into the tail vein (6.4 ± 1.9 MBq; 0.63 ± 0.58 nmol/kg; A_m: 1,016 ± 712 GBq/μmol (EOS) for the 2 months treated serie) or retro-orbital (6.5 ± 2.4 MBq; 0.18 ± 0.18 nmol/kg; A_m: 4,460 ± 2,115 GBq/μmol (EOS); for the 4 months treated serie) followed by a 60-min PET/MR scan (Mediso nanoScan®, Budapest, Hungary). A T1-weighted WB gradient echo sequence (GRE, repetition time = 20 ms, echo time = 6.4 ms) was performed for AC and anatomical orientation. The reconstruction parameters for the list mode data were the following: 3D-ordered subset expectation maximization (OSEM), four iterations, six subsets. The mice were positioned prone in a special mouse bed (heated up to 37°C), with the head fixed to a mouth piece for the anesthetic gas supply with isoflurane in 40% air and 60% oxygen (anesthesia unit: U-410, Agnthos, Lidingö, Sweden; gas blender: MCQ, Rome, Italy), image co-registration and evaluation of the volume of interest (VOI) were performed with PMOD (PMOD Technologies LLC, v. 3.9, Zurich, Switzerland). Spherical VOI with diameters of 1 to 2 mm were placed at the center of the caecum on the PET/MR fusion image. For the jejunum the VOI was delineated from the PET signal. The activity concentrations in the VOIs are expressed as the mean standardized uptake values (SUV) +/− SEM.