PET study using [¹¹C]FTIMD with ultra-high specific activity to evaluate I₂-imidazoline receptors binding in rat brains

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• 作者：Kazunori Kawamura^a ; ^{kawamur@nirs.go.jp} ; Yuichi Kimura^b ; Joji Yui^a ; Hidekatsu Wakizaka^c ; Tomoteru Yamasaki^a ; Akiko Hatori^a ; Katsushi Kumata^a ; Masayuki Fujinaga^a ; Yuichiro Yoshida^a ; ^d ; Masanao Ogawa^a ; ^d ; Nobuki Nengaki^a ; ^d ; Toshimitsu Fukumura^a ; Ming-Rong Zhang^a
• 关键词：Ultra-high specific activity ; Imidazoline receptors ; I2 ; FTIMD ; 11C ; PET
• 刊名：Nuclear Medicine and Biology
• 出版年：2012
• 出版时间：February 2012
• 年：2012
• 卷：39
• 期：2
• 页码：199-206
• 全文大小：425 K

文摘

Introduction

We recently developed a selective ¹¹C-labeled I₂-imidazoline receptor (I₂R) ligand, 2-(3-fluoro-4-[¹¹C]tolyl)-4,5-dihydro-1H-imidazole ([¹¹C]FTIMD). [¹¹C]FTIMD showed specific binding to I₂Rs in rat brains having a high density of I₂R, as well as to I₂Rs those in monkey brains, as illustrated by positron emission tomography (PET) and autoradiography. However, [¹¹C]FTIMD also showed moderate non-specific binding in rat brains. In order to increase the specificity for I₂R in rat brains, we synthesized [¹¹C]FTIMD with ultra-high specific activity and evaluated its binding.

Methods

[¹¹C]FTIMD with ultra-high specific activity was prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [¹¹C]methyl iodide, which was produced by iodination of [¹¹C]methane using the single-pass method. Dynamic PET scans were conducted in rats, and the kinetic parameters were estimated.

Results

[¹¹C]FTIMD with ultra-high specific activity was successfully synthesized with an appropriate level of radioactivity and ultra-high specific activity (4470¡À1660 GBq/¦Ìmol at end of synthesis, n=11) for injection. In the PET study, distribution volume (V_T) values in all the brain regions investigated whether I₂R expression was greatly reduced in BU224-pretreatead rats compared with control rats (29-45 % decrease). Differences in V_T values between control and BU224-pretreated rats using [¹¹C]FTIMD with ultra-high specific activity were greater than those using [¹¹C]FTIMD with normal specific activity (17-34 % decrease) in all brain regions investigated.

Conclusion

Quantitative PET using [¹¹C]FTIMD with ultra-high specific activity can contribute to the detection of small changes in I₂R expression in the brain.