Estimation of Oxygen Metabolism in a Rat Model of Permanent Ischemia Using Positron Emission Tomography with Injectable 15O-O2

Temma, Takashi; Magata, Yasuhiro; Kuge, Yuji; Shimonaka, Sayaka; Sano, Kohei; Katada, Yumiko; Kawashima, Hidekazu; Mukai, Takahiro; Watabe, Hiroshi; Iida, Hidehiro; Saji, Hideo

doi:10.1038/sj.jcbfm.9600302

Cited by 18 publications

(23 citation statements)

References 22 publications

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“…Although the steady-state method may induce systemic underestimation of CBF because of tissue heterogeneity between gray and white matter as compared with the bolus injection method in the human study (Kanno et al, 1984); however, the structure of the brain cortex in rats is not so complicated (Zilles and Wree, 1995), and the effect of brain tissue heterogeneity is not considered so significant as compared with the human brain because we placed ROIs on the cortices ( Figure 3A) and basal ganglia. The cerebral hemodynamic parameters of the normal rats using the present steady-state method were similar to the results reported previously using the bolus method (Magata et al, 2003;Temma et al, 2006;Tiwari et al, 2010), in which slightly higher values of OEF and CMRO 2 in normal rats were observed compared with those of normal human subjects. Differences in species and effects of anesthesia during the experiments are considered to provide these differences.…”

Section: Discussionsupporting

confidence: 88%

“…Although the P CO2 values in the MCAO model rats were significantly decreased compared with those in the normal rats, probably due to hyperventilation in a few rats during PET experiments, the CBF was not affected significantly because other blood gas data were not changed compared with those of normal rats. This effect of MCAO operation on the arterial blood gas data was similar to a previous report (Temma et al, 2006). The P CO2 values seem slightly higher and the P O2 values seem slightly lower in normal rats compared with those in humans probably due to the tendency of hypoventilation under anesthesia during Figure 1 Time-activity curves of the whole blood, plasma, and the whole brain using 15 O 2 -HbV with the steady-state method.…”

Section: Discussionsupporting

confidence: 87%

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Cerebral Oxygen Metabolism of Rats using Injectable ¹⁵O-Oxygen with a Steady-State Method

Kobayashi

Mori

Kiyono

et al. 2011

J Cereb Blood Flow Metab

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To develop a less-stressful and simple method for measurement of the cerebral metabolic rate of oxygen (CMRO 2 ) in small animals, the steady-state method was applied to injectable 15 O 2 -PET ( 15 O 2 -positron emission tomography) using hemoglobin-containing vesicles ( 15 O 2 -HbV). Ten normal rats and 10 with middle cerebral arterial occlusion (MCAO) were studied using a small animal PET scanner. A series of 15 O-PET scans with C 15 O-labeled HbV, H 2 15 O, and 15 O 2 -HbV were performed with 10 to 15 minutes intervals to measure cerebral blood volume (CBV), cerebral blood flow (CBF), and CMRO 2 . Positron emission tomography scans were started with a tracer injection using a multiprogramming syringe pump, which provides a slowly increasing injection volume to achieve steady-state radioactivity for H 2 15 O and 15 O 2 -HbV scans. The radioactivity concentration of 15 O rapidly achieved equilibrium in the blood and whole brain at about 2 minutes after H 2 15 O and 15 O 2 -HbV administration, which was stable during the scans. The whole brain mean values of CBF, CBV, and CMRO 2 were 54.3 ± 2.0 mL per 100 g per minute, 4.9 ± 0.4 mL/100 g, and 2.8 ± 0.2 lmoL per g per minute (6.2±0.4 mL per 100 g per minute) in the normal rats, respectively. In the MCAO model rats, all hemodynamic parameters of the infarction area on the occlusion side significantly decreased. The steady-state method with 15 O-labeled HbV is simple and useful to analyze hemodynamic changes in studies with model animals.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 87%

Cerebral Oxygen Metabolism of Rats using Injectable ¹⁵O-Oxygen with a Steady-State Method

Kobayashi

Mori

Kiyono

et al. 2011

J Cereb Blood Flow Metab

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“…The third is the limited volume of the tracer solution that can be injected into small animals. To overcome these technical difficulties, some previous studies have applied 15 O gas inhalation through a tracheal tube (3), venous injection of 15 O-O 2 hemoglobin-containing red blood cells (4,5), 15 O-CO or O 2 hemoglobin-containing vesicles (6), or liposome-encapsulated hemoglobin (7). For quantitative measurements, the radioactivity of the cardiac chambers has been measured (3).…”

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confidence: 99%

Quantitative Evaluation of Cerebral Blood Flow and Oxygen Metabolism in Normal Anesthetized Rats: ¹⁵O-Labeled Gas Inhalation PET with MRI Fusion

et al. 2013

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PET with 15 O gas has been used for the quantitative measurement of cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO 2 ), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) in humans. However, several technical difficulties limit its use in experiments on small animals. Herein, we describe the application of the 15 O gas steady-state inhalation method for normal anesthetized rats. Methods: Eight normal male Sprague-Dawley rats (mean body weight 6 SD, 268 6 14 g) under anesthesia were investigated by 15 O-labeled gas PET. After tracheotomy, an airway tube was placed in the trachea, and the animals were connected to a ventilator (tidal volume, 3 cm 3 ; frequency, 60/min). The CBF and OEF were measured according to the original steady-state inhalation technique under artificial ventilation with 15 O-CO 2 and 15 O-O 2 gases delivered through the radioactive gas stabilizer. CBV was measured by 15 O-CO gas inhalation and corrected for the intravascular hemoglobinbound 15 O-O 2 . Arterial blood sampling was performed during each study to measure the radioactivity of the whole blood and plasma. MR image was performed with the same acrylic animal holder immediately after the PET. Regions of interest were placed on the whole brain of the PET images with reference to the semiautomatically coregistered PET/MR fused images. Results: The data acquisition time for the whole PET experiment in each rat was 73.3 6 5.8 (range, 68-85) min. In both the 15 O-CO 2 and the 15 O-O 2 studies, the radioactivity count of the brain reached a steady state by approximately 10 min after the start of continuous inhalation of the gas. The quantitative PET data of the whole brain were as follows: CBF, 32.3 6 4.5 mL/100 mL/min; CMRO 2 , 3.23 6 0.42 mL/100 mL/min; OEF, 64.6% 6 9.1%; and CBV, 5.05 6 0.45 mL/100 mL. Conclusion: Although further technical improvements may be needed, this study demonstrated the feasibility of quantitative PET measurement of CBF, OEF, and CMRO 2 using the original steady-state inhalation method of 15 O-CO 2 and 15 O-O 2 gases and measurement of CBV using the 15 O-CO gas inhalation method in the brain of normal anesthetized rats.

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“…Consequently, we found that hypertension intensifies metabolic disturbances after the onset of strokes. [90][91][92][93] Thus injectable 15 O-O 2 could be used reliably to estimate oxygen metabolism in an infarction rat model with PET. Furthermore, we developed molecular probes for nuclear medicinal imaging targeting β-secretase in the brain, acetylcholine esterase, cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), and hepatic organic anion transporter (OATP1B1).…”

Section: Tc or 186/188mentioning

confidence: 99%

In Vivo Molecular Imaging

Saji

2017

Biological & Pharmaceutical Bulletin

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In vivo molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Among the methodologies used in in vivo molecular imaging, two methodologies are of great interest from the view of high sensitivity. One is nuclear medical imaging, and distribution and kinetics of a radiolabeled molecular probe are measured using positron emission tomography (PET) and single-photon emission computed tomography (SPECT). The other is optical molecular imaging, and distribution and kinetics of a fluorescent probe are measured using a fluorescent imaging instrument. In this review, the development of imaging probes for these two methodologies is briefly discussed. In nuclear medical molecular imaging, based on structure-activity-biodistribution relationship studies for small molecule and the concept of "functional unit-binding multifunctional molecular probe" containing 3 functional units (target recognition unit, signal-releasing unit, linker unit) for peptides and proteins, we developed radiolabeled probes with high and specific accumulation to the target for neuroreceptors, β-amyloid plaques, and tau aggregates in the brain, tumors, atherosclerotic plaques, pancreatic β-cell, myocardial sympathetic nerves, and so on. We also discuss the progression of molecular imaging toward therapy (radiotheranotics). In in vivo optical molecular imaging, taking into account the characteristics of optical imaging, we designed tumor-specific optical imaging probes with characteristic imaging mechanism, including near-infrared (NIR) fluorescent probes and activatable probes. Furthermore, we developed a photoacoustic imaging probe, which enables highly sensitive and high-resolution imaging in deep tissues.

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Estimation of Oxygen Metabolism in a Rat Model of Permanent Ischemia Using Positron Emission Tomography with Injectable ¹⁵O-O₂

Cited by 18 publications

References 22 publications

Cerebral Oxygen Metabolism of Rats using Injectable ¹⁵O-Oxygen with a Steady-State Method

Cerebral Oxygen Metabolism of Rats using Injectable ¹⁵O-Oxygen with a Steady-State Method

Quantitative Evaluation of Cerebral Blood Flow and Oxygen Metabolism in Normal Anesthetized Rats: ¹⁵O-Labeled Gas Inhalation PET with MRI Fusion

<i>In Vivo</i> Molecular Imaging

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Estimation of Oxygen Metabolism in a Rat Model of Permanent Ischemia Using Positron Emission Tomography with Injectable 15O-O2

Cited by 18 publications

References 22 publications

Cerebral Oxygen Metabolism of Rats using Injectable 15O-Oxygen with a Steady-State Method

Cerebral Oxygen Metabolism of Rats using Injectable 15O-Oxygen with a Steady-State Method

Quantitative Evaluation of Cerebral Blood Flow and Oxygen Metabolism in Normal Anesthetized Rats: 15O-Labeled Gas Inhalation PET with MRI Fusion

<i>In Vivo</i> Molecular Imaging

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Estimation of Oxygen Metabolism in a Rat Model of Permanent Ischemia Using Positron Emission Tomography with Injectable ¹⁵O-O₂

Cerebral Oxygen Metabolism of Rats using Injectable ¹⁵O-Oxygen with a Steady-State Method

Cerebral Oxygen Metabolism of Rats using Injectable ¹⁵O-Oxygen with a Steady-State Method

Quantitative Evaluation of Cerebral Blood Flow and Oxygen Metabolism in Normal Anesthetized Rats: ¹⁵O-Labeled Gas Inhalation PET with MRI Fusion