Quantification of regional myocardial oxygen metabolism in normal pigs using positron emission tomography with injectable 15O-O2

Temma, Takashi; Iida, Hidehiro; Hayashi, Takuya; Teramoto, Noboru; Ohta, Yoshihiro; Kudomi, Nobuyuki; Watabe, Hiroshi; Saji, Hideo; Magata, Yasuhiro

doi:10.1007/s00259-009-1262-2

Cited by 9 publications

(9 citation statements)

References 14 publications

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“…In particular, using the injectable 15 O-O 2 PET technique in spontaneously hypertensive rats (SHR), this research group clearly demonstrated that hypertension could intensify cerebral metabolic disturbances during the acute phase after the onset of stroke (Figure 2 [15]). This same group also applied the 15 O-O 2 injection technique to miniature pigs to evaluate myocardial oxygen metabolism, which was also considered to be a difficult target for evaluation by 15 O-O 2 gas inhalation because of the existence of radioactivity spillover from the gas volume in the lung to the myocardium due to limited spatial resolution [17]. Although the blood-based injectable 15 O-O 2 system provided a strong option that enabled oxygen metabolism measurement in small animals under normal and pathological conditions, some drawbacks were addressed for further applications.…”

Section: Intravenous Administration Methodsmentioning

confidence: 99%

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PET Quantification of Cerebral Oxygen Metabolism in Small Animals

Temma

Koshino

Moriguchi

et al. 2014

The Scientific World Journal

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Understanding cerebral oxygen metabolism is of great importance in both clinical diagnosis and animal experiments because oxygen is a fundamental source of brain energy and supports brain functional activities. Since small animals such as rats are widely used to study various diseases including cerebral ischemia, cerebrovascular diseases, and neurodegenerative diseases, the development of a noninvasive in vivo measurement method of cerebral oxygen metabolic parameters such as oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) as well as cerebral blood flow (CBF) and cerebral blood volume (CBV) has been a priority. Although positron emission tomography (PET) with 15O labeled gas tracers has been recognized as a powerful way to evaluate cerebral oxygen metabolism in humans, this method could not be applied to rats due to technical problems and there were no reports of PET measurement of cerebral oxygen metabolism in rats until an 15O-O2 injection method was developed a decade ago. Herein, we introduce an intravenous administration method using two types of injectable 15O-O2 and an 15O-O2 gas inhalation method through an airway placed in the trachea, which enables oxygen metabolism measurements in rats.

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Section: Intravenous Administration Methodsmentioning

confidence: 99%

“…The length of the artificial lung was 6 cm in the original report [13] and was changed to 18 cm in the latter studies for improvement of labeling efficiency [14, 15, 17]. …”

Section: Figurementioning

confidence: 99%

PET Quantification of Cerebral Oxygen Metabolism in Small Animals

Temma

Koshino

Moriguchi

et al. 2014

The Scientific World Journal

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“…Radioprobes derived from low-molecular-weight polypeptides or compounds, small recombinant antibody fragments (Fab, scFv), engineered variants (diabodies, triabodies, minibodies, and single-domain antibodies), or pretargeting antibody methods show rapid clearance of radioactivity from the circulation (19)(20)(21). Image-subtraction techniques (22)(23)(24) or kinetic model analysis (25,26) may also help solve this issue. Accordingly, 99m Tc-TF-mAb or its derivatives have great potential as in vivo molecular imaging probes and deserve further investigation.…”

Section: Limitations Of 99m Tc-tf-mabmentioning

confidence: 99%

Tissue Factor Detection for Selectively Discriminating Unstable Plaques in an Atherosclerotic Rabbit Model

Temma¹,

Ogawa²,

Kuge³

et al. 2010

J Nucl Med

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Tissue factor (TF), a transmembrane glycoprotein that acts as an essential cofactor to factor VII/VIIa, initiates the exogenous blood coagulation cascade leading to thrombin generation and subsequent thrombus formation in vivo. TF expression is closely related to plaque vulnerability, and high TF expression is shown in macrophage-rich atheromatous lesions, making TF a potential target for detecting atheromatous lesions in vivo. Thus, we prepared 99m Tc-labeled anti-TF-monoclonal antibody (TF-mAb) IgG as a molecular probe and evaluated its usefulness to achieve TF-specific imaging using myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits. Methods: Anti-TF-mAb was created using a standard hybridoma technique and was labeled by 99m Tc with 6-hydrazinonicotinic acid (HYNIC) as a chelating agent to obtain 99m Tc-TF-mAb. The immunoreactivity of HYNIC-TF-mAb was estimated by flow cytometry. WHHLMI and control rabbits were injected intravenously with 99m Tc-TF-mAb. Twenty-four hours after the injection, the aorta was removed and radioactivity was measured. Autoradiography and histologic studies were performed using serial aorta sections. Subclass matched antibody (IgG 1 ) was used as a negative control. Results: HYNIC-TF-mAb showed 93% immunoreactivity of the anti-TF-mAb. The radioactivity accumulation in WHHLMI aortas was 6.1-fold higher than that of control rabbits. Autoradiograms showed a heterogeneous distribution of radioactivity in the intima of WHHLMI aortas. Regional radioactivity accumulation was positively correlated with TF expression density (R 5 0.64, P , 0.0001). The highest radioactivity accumulation in percentage injected dose · body weight/mm 2 · 10 2 was found in atheromatous lesions (5.2 6 1.9) followed by fibroatheromatous (2.1 6 0.7), collagen-rich (1.8 6 0.7), and neointimal lesions (1.8 6 0.6). In contrast, 99m Tc-IgG 1 showed low radioactivity accumulation in WHHLMI aortas that was independent of the histologic grade of lesions. Conclusion: The TF-detecting ability and preferential accumulation in atheromatous lesions of 99m Tc-TF-mAb were demonstrated, indicating its potential for selective imaging of macrophage-rich atheromatous lesions in vivo.

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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%

<i>In Vivo</i> 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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Quantification of regional myocardial oxygen metabolism in normal pigs using positron emission tomography with injectable 15O-O2

Abstract: These results indicate that injectable (15)O-O(2) has the potential to evaluate myocardial oxygen metabolism.

Cited by 9 publications

References 14 publications

PET Quantification of Cerebral Oxygen Metabolism in Small Animals

PET Quantification of Cerebral Oxygen Metabolism in Small Animals

Tissue Factor Detection for Selectively Discriminating Unstable Plaques in an Atherosclerotic Rabbit Model

<i>In Vivo</i> Molecular Imaging

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