Imaging of I₂-imidazoline receptors by small-animal PET using 2-(3-fluoro-[4-¹¹C]tolyl)-4,5-dihydro-1H-imidazole ([¹¹C]FTIMD)

详细信息    查看全文

• 作者：Kazunori Kawamura ; Mika Naganawa ; Fujiko Konno ; Joji Yui ; Hidekatsu Wakizaka ; Tomoteru Yamasaki ; Kazuhiko Yanamoto ; Akiko Hatori ; Makoto Takei ; Yuichiro Yoshida ; Kazuya Sakaguchi ; Toshimitsu Fukumura
• 关键词：Imidazoline receptors ; I₂ ; FTIMD ; ¹¹C ; PET
• 刊名：Nuclear Medicine and Biology
• 出版年：2010
• 出版时间：July 2010
• 年：2010
• 卷：37
• 期：5
• 页码：625-635
• 全文大小：1039 K

文摘

Introduction

Imidazoline receptors (IRs) have been established as distinct receptors, and have been categorized into at least two subtypes (I₁R and I₂R). I₂Rs are associated with depression, Alzheimer's disease, Huntington's disease and Parkinson's disease. A few positron emission tomography (PET) probes for I₂Rs have been synthesized, but a selective PET probe has not been evaluated for the imaging of I₂Rs by PET. We labeled a selective I₂R ligand 2-(3-fluoro-4-tolyl)-4,5-dihydro-1H-imidazole (FTIMD) with ¹¹C and performed the first imaging of I₂Rs by PET using 2-(3-fluoro-[4-¹¹C]tolyl)-4,5-dihydro-1H-imidazole ([¹¹C]FTIMD).

Methods

[¹¹C]FTIMD was prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [¹¹C]methyl iodide in the presence of tris(dibenzylideneacetone)dipalladium(0) and tri(o-tol)phosphine. Biodistribution was investigated in rats by tissue dissection. [¹¹C]FTIMD metabolites were measured in brain tissues and plasma. Dynamic PET scans were acquired in rats, and the kinetic parameters estimated.

Results

[¹¹C]FTIMD was successfully synthesized with a suitable radioactivity for the injection. Co-injection with 0.1 mg/kg of cold FTIMD and BU224 induced a significant reduction in the brain-to-blood ratio 15 and 30 min after the injection. In metabolite analysis, unchanged [¹¹C]FTIMD in the brain was high (98 % ) 30 min after the injection. In PET studies, high radioactivity levels were observed in regions with a high density of I₂R. The radioactivity levels and V_T values in the brain regions were prominently reduced by 1.0 mg/kg of BU224 pretreatment as compared with control.

Conclusion

[¹¹C]FTIMD showed specific binding to I₂Rs in rat brains with a high density of I₂R.