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Imaging of Striatal Dopamine D₂ Receptors with a PET System for Small Laboratory Animals in Comparison with Storage Phosphor Autoradiography: A Validation Study with ¹⁸F-(N-Methyl)Benperidol

Department of Nuclear Medicine, Heinrich-Heine-Universität, Düsseldorf, Germany

Several groups have developed high-resolution PET systems and shown the feasibility of in vivo studies on small laboratory animals. In this investigation, one of these systems was validated for the performance of receptor imaging studies. For this, the radiotracer concentrations obtained in the same animals with PET and with autoradiography were quantified, and the correspondence between both methods was assessed by means of correlation analysis. Methods: Striatal radioactivity was measured in 10 Sprague–Dawley rats after injection of 60 ± 10 MBq of the dopamine D₂ receptor ligand ¹⁸F-(N-methyl)benperidol in 6 time frames of 6 min each. On completion of the scans, animals were killed, and their brains were removed and sectioned using a cryostat microtome. Coronal slices were subjected to storage phosphor autoradiography with BaFBr:Eu²⁺-coated imaging plates. Striatal radioactivity was quantified in both modalities using region-of-interest analysis and activity standards. Results: After partial-volume correction, the median of striatal radioactivity concentration measured with PET was 0.40 MBq/cm³ (25th percentile, 0.32; 75th percentile, 0.44). Radioactivity concentrations determined by means of storage phosphor autoradiography amounted to 0.42 MBq/cm³ (25th percentile, 0.24; 75th percentile, 0.51). Correlation of striatal radioactivity values yielded a Pearson correlation coefficient of 0.818 (P = 0.002). Radioactivity accumulation in Harder’s glands led to an overestimation of striatal activity concentrations by approximately 5%. The median of striatal radioactivity concentration after spillover correction decreased slightly to 0.38 MBq/cm³ (25th percentile, 0.30; 75th percentile, 0.43). Correlation of striatal radioactivity values after spillover correction yielded a Pearson correlation coefficient of 0.824 (P = 0.002). Conclusion: The results show a significant positive correlation between radioactivity values obtained with PET and storage phosphor autoradiography used as the gold standard. Because we applied a selective dopamine D₂ receptor radioligand and because radioactivity concentrations could be reliably quantified in the target region, we may infer that in vivo receptor binding studies will be possible in small laboratory animals.

Key Words: animal PET • phosphor screen imaging • dopamine D₂ receptors • ¹⁸F-(N-methyl)benperidol

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