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Quantitative Analysis of NK₁ Receptor in the Human Brain Using PET with ¹⁸F-FE-SPA-RQ

¹ Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; ² Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan; ³ Department of Pharmacology, Nippon Medical School, Tokyo, Japan; and ⁴ Molecular Probe Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan

Correspondence: For correspondence or reprints contact: Hiroshi Ito, Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences 4-9-1, Anagawa, Inage-ku, Chiba, 263-8555, Japan. E-mail: hito{at}nirs.go.jp

¹⁸F-fluoroethyl-SPA-RQ (¹⁸F-FE-SPA-RQ) was recently developed as a radioligand for the measurement of neurokinin 1 (NK₁) receptor with PET. In this study, we used ¹⁸F-FE-SPA-RQ with PET to visualize and quantify NK₁ receptor in the human brain. Methods: PET scans were performed on 7 healthy men after intravenous injection of ¹⁸F-FE-SPA-RQ. Binding potential (BP_ND) was calculated by the indirect kinetic, simplified reference tissue model (SRTM), and ratio methods. The indirect kinetic method was used as the gold standard method and was compared with the SRTM method, with scan times of 180, 270, and 330 min, and with the ratio method, with time integration intervals of 120–180, 210–270, and 300–330 min. The cerebellum was used as the reference brain region. Results: Regional radioactivity was highest in the caudate head and putamen; mid level in the parahippocampus, cerebral cortex, and thalamus; and lowest in the cerebellum. BP_ND values by the indirect kinetic method were 3.15 ± 0.36, 3.11 ± 0.66, 1.17 ± 0.25, and 0.46 ± 0.14 in the caudate, putamen, parahippocampal region, and thalamus, respectively. For cerebral cortical regions, BP_ND values by the indirect kinetic method were 0.94 ± 0.23, 0.82 ± 0.15, 0.76 ± 0.15, and 0.69 ± 0.16 in the occipital, temporal, frontal, and anterior cingulate cortices, respectively. BP_ND values by the SRTM and ratio methods were in good agreement with those by the indirect kinetic method (r = 0.94–0.98). Conclusion: The regional distribution of ¹⁸F-FE-SPA-RQ was in agreement with previous PET studies and postmortem studies of NK₁ receptor in the human brain. The ratio method will be useful for clinical research of psychiatric disorders, for the estimation of NK₁ receptor without arterial blood sampling and long dynamic PET.

Key Words: NK₁ receptor • substance P • ¹⁸F-FE-SPA-RQ • PET • human brain

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JNM 2008 49: 11A-12A. [Full Text]