Effect of Animal Condition and Fluvoxamine on the Result of [(18)F]N-3-Fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) Nortropane ([(18)F]FP-CIT) PET Study in Mice

Abstract

Purpose: PET (positron emission tomography) is a noninvasive imaging technique, visualizing biological aspects in vivo. In animal models, the result of PET study can be affected more prominently than in humans by the animal conditions or drug pretreatment. We assessed the effects of anesthesia, body temperature, and pretreatment with selective serotonin reuptake inhibitor on the results of [(18)F]N-3-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([(18)F]FP-CIT) PET in mice.

Methods: [(18)F]FP-CIT PET of C57BL/6 mice was performed in three different conditions: (1) anesthesia (isoflurane) with active warming (38°C) as a reference; (2) no anesthesia or warming; (3) anesthesia without warming at room temperature. Additional groups of mice pretreated with escalating doses of fluvoxamine (5, 20, 40, 80 mg/kg) were imaged in condition (1). The time activity curve and standardized uptake value of the striatum, cerebral cortex, and bone were compared among these conditions.

Results: In all conditions, radioactivities of the striatum and cortex tended to form a plateau after rapid uptake and washout, but that of bone tended to increase gradually. When anesthetized without any warming, all the mice developed hypothermia and showed reduced bone uptake with slightly increased striatal and cortical uptakes compared to the reference condition. In conditions without anesthesia, striatal and cortical uptakes were reduced, whereas the bone uptake showed no change. Pretreatment with fluvoxamine increased the striatal uptake and striatal specific to cortical non-specific uptake ratio, whereas the bone uptake was reduced.

Conclusion: Anesthesia, body temperature, and fluvoxamine affect the result of [(18)F]FP-CIT PET in mice by altering striatal and bone uptakes.

Keywords: Anesthesia; Fluvoxamine; Mice; PET; Temperature; [18F]FP-CIT.

Fig. 1

Possible radiometabolites of [¹⁸F]FP-CIT. (a) The hydrolysis of ester gives rise to [¹⁸F]FP-CIT acid, the major metabolite found in plasma. (b) The N-dealkylation by cytochrome P450 isoenzymes leads to the formation of [¹⁸F]fluoropropyl. (c) The defluorination by cytochrome P450 isoenzymes leads to the formation of [¹⁸F]fluoride

Fig. 2

Time activity curve of the striatum, cortex, and bone uptake at reference condition (anesthesia with warming). SUV of the striatum and cortex show plateau after rapid uptake and washout, but SUV of the bone tended to increase gradually after rapid uptake and washout

Fig. 3

PET images of each condition at post-injection 90 min (left top: coronal, right top: sagittal, left bottom: axial, right bottom: MIP image). (a) PET images obtained under anesthesia with warming, which is the reference condition, shows faint striatal uptake (arrowhead) and strong bone uptake (arrow). (b) In a condition of neither anesthesia nor warming, PET image shows faint uptake in the striatum (arrowheads) and prominent uptake in the bone (arrow). (c) PET image acquired under anesthesia without warming shows increased striatal uptake (arrowhead) but reduced bone uptake (arrow), compared to the reference condition

Fig. 4

SUV or SUV ratios of target organs in each group. Compared to group 1 (anesthesia with warming, reference), group 2 (no anesthesia or warming) shows reduced striatal and cortical uptakes, and no significant change in the bone uptake. Group 3 (anesthesia without warming) shows markedly reduced bone uptake with slightly increased striatal and cortical uptakes compared to the reference condition. (Specific: striatal specific activity; Spc/Crt: striatal specific activity/cortical non-specific activity; Bn/Str: bone activity/striatal activity)

Fig. 5

SUV or SUV ratios of target organs with escalating dose (0, 5, 20, 40, 80 mg/kg) of fluvoxamine. Serially increased striatal uptake, especially at the dose of 40 mg/kg, without significant changes in the cortical uptake can be seen along with gradually reduced bone uptake as the fluvoxamine dose increases. There also was an increase in the striatal specific to cortical non-specific activity ratio (Spc/Crt), whereas the bone to striatal uptake ratio (Bn/Str) decreased. (Specific: striatal specific activity; Spc/Crt: striatal specific activity/cortical non-specific activity; Bn/Str: bone activity/striatal activity)