PET Imaging of Brain 5-HT1A Receptors in Rat In Vivo with 18F-FCWAY and Improvement by Successful Inhibition of Radioligand Defluorination with Miconazole

PET Imaging of Brain 5-HT_1A Receptors in Rat In Vivo with ¹⁸F-FCWAY and Improvement by Successful Inhibition of Radioligand Defluorination with Miconazole

Dnyanesh N. Tipre, PhD¹, Sami S. Zoghbi, PhD¹, Jeih-San Liow, PhD¹, Michael V. Green, MS², Jurgen Seidel, PhD³, Masanori Ichise, MD¹, Robert B. Innis, PhD¹ and Victor W. Pike, PhD¹

¹ Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland; ² Trident Imaging, Inc., Rockville, Maryland; and ³ Imaging Physics Laboratory, National Institute for Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland

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FIGURE 1. Time–activity curves in frontal cortex ( ${triangleup}$ ), frontal hippocampus ( ${triangledown}$ ), ventral hippocampus ( ${diamond}$ ), cerebellum (*), and brain ( ${square}$ ) in rats infused intravenously for 45 min with 0 (A), 15 (B), 30 (C), or 60 (D) mg/kg of miconazole nitrate immediately before being injected intravenously with ¹⁸F-FCWAY (33.3–48.1 MBq). Each panel shows data from 1 rat.

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FIGURE 2. Ratios of radioactivity in the ROIs frontal cortex ( ${triangleup}$ ), frontal hippocampus ( ${triangledown}$ ), and ventral hippocampus ( ${diamond}$ ) to that in cerebellum after intravenous injection of ¹⁸F-FCWAY into rats under baseline conditions (A) or in rats treated with 60 mg/kg miconazole nitrate (B). C and D show, for the experiments presented in A and B, respectively, the level of 5-HT_1A receptor-specific binding in frontal cortex ( ${triangleup}$ ), frontal hippocampus ( ${triangledown}$ ), and ventral hippocampus ( ${diamond}$ ), expressed in percentage SUV of the difference in radioactivity concentration between brain tissue of interest and cerebellum Each panel shows data from 1 rat.

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FIGURE 3. PET scans of the head acquired between 50 and 60 min after intravenous injection of rat with ¹⁸F-fluoride ion (A), ¹⁸F-FCWAY (B), miconazole nitrate (15 mg/kg intravenously) and then ¹⁸F-FCWAY (C), miconazole nitrate (30 mg/kg intravenously) and then ¹⁸F-FCWAY (D), and miconazole nitrate (60 mg/kg intravenously) and then ¹⁸F-FCWAY (E). % of Max = percentage of maximum.

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FIGURE 4. Time–activity curves in skull in rats treated with 0 ( ${square}$ ), 15 ( ${triangleup}$ ), 30 ( ${triangledown}$ ), or 60 ( ${diamond}$ ) mg/kg of miconazole nitrate immediately before intravenous injection of ¹⁸F-FCWAY. Each panel shows data from 1 rat.

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FIGURE 5. Skull (A) and brain (B) radioactivities (% SUV) measured in vivo with PET and ex vivo at 90 min after ¹⁸F-FCWAY injection in rats treated with 0, 15, 30, and 60 mg/kg miconazole nitrate.

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FIGURE 6. Time–activity curves in ventral hippocampus ( ${triangleup}$ ), brain ( ${square}$ ), and skull ( ${triangledown}$ ) after intravenous injection of ¹⁸F-fluoride ion into rats. Each panel shows data from 1 rat.