New PET diagnosis of adenosine receptors in the brain, heart and skeletal muscle

大脑、心脏和骨骼肌腺苷受体的新 PET 诊断

• 批准号: 16390348
• 负责人: ISHIWATA Kiichi
• 金额: $ 9.09万
• 依托单位: Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390348/
• 关键词: Adenosine receptor; PET; [^<11>C]MPDX; [^<11>C]TMSX; Brain; Heart; Muscle; アルツハイマー病; パーキンソン病; てんかん; 加齢; P糖タンパク質

The purpose of the present study is to propose new PET diagnosis using [^<11>C]MPDX and [^<11>C]TMSX for imaging adenosine A_1 and A_<2A> receptors, respectively, in the brain, heart and muscle1. By applying [^<11>C]MPDX-PET and [^<11>C]TMSX-PET to normal subjects, A_1 and A_<2A> receptors, respectively, was quantitatively measured by compartment and graphical analyses using dynamic PET scan and serial arterial blood data.2. To avoiding invasive arterial blood sampling, a non-invasive quantitative method EPICA was successfully applied to both[^<11>C]MPDX-and [^<11>C]TMSX-PET.3. In the patients with Alzheimer's disease, a significantly decreased binding of [^<11>C]MPDX was observed in the bilateral medial temporal cortex and left temporo-parietal cortex. The decreased binding pattern of [^<11>C]MPDX was different from hypometabolism. In the patients with temporal lobe epilepsy, binding of [^<11>C]MPDX was significantly decreased in the mesial temporal lobe of focus side outside the hippocampus, but increased in the frontal cortex of focus side.4. In the patients with Parkinson's disease whose the left-side dopamine transporter was more decreased than the right side one, the dopamine D_2 receptors bindings was increased bilaterally, while the adenosine A_<2A> receptor was decreased on the left side.5. Following animal experiments, adenosine A_<2A> receptors in the heart and muscle were quantitatively evaluated in normal subjects. Adenosine A_<2A> receptor binding in the cardiac and skeletal muscles was greater in the endurance-trained men than in the untrained men.We concluded that [^<11>C]MPDX-PET and [^<11>C]TMSX-PET provides diagnostic tools of the physiological and pathological states of various diseases in term of adenosine receptors.

本研究的目的是提出新的PET诊断使用[^<11>C]MPDX和[^<11>C]TMSX成像腺苷A_1和A_<2A>受体，分别在大脑，心脏和肌肉1。应用[^<11>C]MPDX-PET和[^<11>C]TMSX-PET分别对正常人进行A_1和A_<2A>受体的定量测定。为了避免动脉血的无创采集，将EPICA无创定量方法成功应用于[^<11>C] MPDX-PET和[^<11>C]TMSX-PET。在阿尔茨海默病患者中，<11>在双侧内侧颞叶皮层和左侧颞顶叶皮层观察到[^ C]MPDX的结合显著减少。[^ C]MPDX结合模式的降低<11>与代谢低下不同。颞叶癫痫患者<11>海马外侧病灶侧内侧颞叶[^ C]MPDX结合明显减少，而病灶侧额叶皮质[^ C]MPDX结合明显增加.帕金森病患者左侧多巴胺转运体比右侧降低者，双侧多巴胺D_2受体结合增加，而腺苷A_<2A>受体在左侧降低.在动物实验后，<2A>对正常人心肌腺苷A_受体进行了定量测定。结果<2A>表明，运动训练组的心肌和骨骼肌腺苷A受体结合率高于未训练组，说明[^<11>C]MPDX-PET和[^<11>C]TMSX-PET可作为腺苷受体诊断各种疾病的生理和病理状态的工具。

项目成果

Quantitative analysis of adenosine A1 receptors in human brain using positron emission tomography and [1-methyl-11C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine

• DOI: 10.1016/j.nucmedbio.2004.06.005
• 发表时间: 2004-11-01
• 期刊: NUCLEAR MEDICINE AND BIOLOGY
• 影响因子: 3.1
• 作者: Kimura, Y;Ishii, K;Ishiwata, K
• 通讯作者: Ishiwata, K

Improved synthesis of [11C]SA4503, [11C]MPDX and [11C]TMSX by use of [11C]methyl triflate

使用 [11C] 三氟甲磺酸甲酯改进 [11C]SA4503、[11C]MPDX 和 [11C]TMSX 的合成

• 发表时间: 2004
• 期刊: Annals of Nuclear Medicine
• 影响因子: 2.6
• 作者: K. Kawamura;K. Ishiwata
• 通讯作者: K. Ishiwata

Potential of [^<11>C]TMSX for evaluation of adenosine A_<2A> receptors in the skeletal muscle by positron emission tomography.

[^ 11 C]TMSX通过正电子发射断层扫描评估骨骼肌中腺苷A_ 2A 受体的潜力。

• 发表时间: 2004
• 期刊: Nucl.Med.Biol 31(7)
• 作者: Ishiwata K;Mizuno M;Kimura Y;Kawamura K;Oda K;Sasaki T;Nakamura Y;Muraoka;Ishii K
• 通讯作者: Ishii K

In vivo evaluation of P-glycoprotein modulation of eight PET radioligands used clinically.

临床使用的八种 PET 放射性配体 P-糖蛋白调节的体内评估。

• 发表时间: 2007
• 期刊: J. Nucl. Med. 48・1
• 作者: Ishiwata K;Kawamura K;Yanai K;Hendrikse NH
• 通讯作者: Hendrikse NH

Greater adenosine A_<2A> receptor densities in cardiac and skeletal muscle in endurance trained men : a [^<11>]TMSX PET study

接受过耐力训练的男性心肌和骨骼肌中的腺苷 A_<2A> 受体密度更高：[^<11>]TMSX PET 研究

• 发表时间: 2005
• 期刊: Nuclear Medicine and Biology 32・8
• 作者: Mizuno M;Kimura K;Tokizawa K;Ishii K;Oda K;Sasaki T;Nakamura Y;Muraoka I;Ishiwata K.
• 通讯作者: Ishiwata K.