Automatic labeling method for injectable ¹⁵O-oxygen using hemoglobin-containing liposome vesicles and its application for measurement of brain oxygen consumption by PET

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• 作者：Vijay Narayan Tiwari ; Yasushi Kiyono ; Masato Kobayashi ; Tetsuya Mori ; Takashi Kudo ; Hidehiko Okazawa ; Yasuhisa Fujibayashi
• 关键词：Hemoglobin vesicle (HbV) ; Injectable ¹⁵O-O₂ ; l-cysteine ; Cerebral metabolic rate of oxygen (CMRO₂) ; Positron emission tomography (PET)
• 刊名：Nuclear Medicine and Biology
• 出版年：2010
• 出版时间：January 2010
• 年：2010
• 卷：37
• 期：1
• 页码：77-83
• 全文大小：323 K

文摘

Introduction

The aim of this study was to develop an injectable ¹⁵O-O₂ system using hemoglobin-containing vesicles (HbV), a type of artificial red blood cell, and to investigate the feasibility of ¹⁵O₂-labeled HbV (¹⁵O₂-HbV) to measure cerebral metabolic rate of oxygen (CMRO₂) in rats.

Methods

The direct bubbling method was combined with vortexing to enhance labeling efficiency of HbV with ¹⁵O-O₂ gas. l-Cysteine was added as a reductant to protect hemoglobin molecules in HbV from oxidation at different concentrations, and labeling efficiencies were also compared. Measurement of cerebral blood flow (CBF) and CMRO₂ in five normal rats was performed using a small animal PET scanner after the injection of H₂¹⁵O and ¹⁵O₂-HbV to evaluate the precision of hemodynamic parameters quantitatively.

Results

The labeling efficiency of HbV was significantly increased when vortexing and bubbling were combined compared with the simple bubbling method (P<.05). The most efficient method for labeling was bubbling of ¹⁵O-O₂ combined with vortexing and the addition of 2.8 mM l-cysteine in HbV solution. The mean radioactivity of 214.4±7.8 MBq/mL HbV was obtained using this method. PET scans using ¹⁵O₂-HbV and H₂¹⁵O yielded a mean CMRO₂ value of 6.8±1.4 (mL/min per 100 g) in rats with normal CBF of 51.4±7.9 (mL/min per 100 g).

Conclusion

Addition of l-cysteine to HbV and simple direct bubbling of ¹⁵O-O₂ gas combined with vortexing was the most efficient method for preparation of ¹⁵O₂-HbV. The present injectable system using ¹⁵O₂-HbV was successfully utilized to measure CMRO₂ in rats, indicating that this new method could be useful for animal models to measure oxygen metabolism in the brain.