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Reproducibility of ¹¹C-Raclopride Binding in the Rat Brain Measured with the MicroPET R4: Effects of Scatter Correction and Tracer Specific Activity

¹ Chemistry Department, Brookhaven National Laboratory, Upton, New York
² Medical Department, Brookhaven National Laboratory, Upton, New York
³ Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York
⁴ Department of Applied Mathematics and Statistics, State University of New York at Stony Brook, Stony Brook, Stony Brook, New York

A new generation of commercial animal PET cameras may accelerate drug development by streamlining preclinical testing in laboratory animals. However, little information on the feasibility of using these machines for quantitative PET in small animals is available. Here we investigate the reproducibility of microPET imaging of ¹¹C-raclopride in the rat brain and the effects of tracer-specific activity and photon scatter correction on measures of D2 receptor (D2R) availability. Methods: Sprague-Dawley rats (422 ± 29 g; n = 7) were anesthetized with ketamine/xylazine and catheterized for tail vein injection of ¹¹C-raclopride. Each animal was positioned prone in the microPET, centering the head in the field of view. MicroPET data was collected for 60 min—starting at ¹¹C-raclopride injection—and binned into 24 time frames (6 x 10 s, 3 x 20 s, 8 x 60 s, 4 x 200 s, 3 x 600 s). In 3 studies, ¹¹C-raclopride was administered a second time in the same animal, with 2–4 h between injections. In a fourth animal, raclopride (1 mg/kg) was coinjected with ¹¹C-raclopride for the second injection. Three rats received a single dose of ¹¹C-raclopride. The range of doses for all studies was 6.11–18.54 MBq (165–501 µCi). The specific activity at injection was 4.07–48.1 GBq/µmol (0.11–1.3 Ci/µmol). Region-of-interest analysis was performed and the distribution volume ratio (DVR) was computed for striatum/cerebellum using sinograms uncorrected and corrected for scatter using a tail-fit method. Results: Test-retest results showed that the ¹¹C-raclopride microPET DVR was reproducible (change in DVR = -8.3% ± 4.4%). The average DVR from 6 rats injected with high specific activity (<4 nmol/kg) was 2.43 ± 0.19 (coefficient of variation = 8%). The DVR for the blocking study was 1.23. The DVR depended on the mass of tracer ¹¹C-raclopride injected for doses >1.5 nmol/kg. Scatter fractions within the rat head were 25%–45% resulting in an average increase of DVR of 3.5% (range, 0%–10%) after correction. Conclusion: This study shows that the ¹¹C-raclopride microPET-derived DVR is reproducible and suitable for studying D2R availability in the rat brain. MicroPET sensitivity was sufficient to determine reproducible DVRs from ¹¹C-raclopride injections of 9.25 MBq (250 µCi). However, the effect of tracer mass on the DVR should be considered for studies using more than 1–2 nmol/kg raclopride, and scatter correction has a measurable impact on the results.

Key Words: microPET • rat brain • dopamine receptor • raclopride

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