Continuous Wave Electron Paramagnetic Resonance Imaging

连续波电子顺磁共振成像

• 批准号: 8552704
• 负责人: murali cherukuri
• 金额: $ 51.21万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8552704
• 关键词: Agreement; Behavior; Carbonates; DNA; Dental Enamel; Dose; Electron Spin Resonance Spectroscopy; Enzymes; Exposure to; Goals; Human; Hydroxide Ion; Hydroxides; Hydroxyapatites; Hypoxia; Image; In Vitro; Ionizing radiation; Ions; Link; Measurement; Mechlorethamine; Methods; Monitor; Oral cavity; Oxidation-Reduction; Oxygen; Pharmaceutical Preparations; Population; Process; Spin Trapping; Superoxides; Time; Triage; Whole-Body Irradiation; azomycin; base; biodosimetry; cytotoxicity; in vivo; inorganic phosphate

TH-302 is a binary chemotherapeutic drug which has a 2-nitroimidazole moiety covalently linked to a DNA alkylating nitrogen mustard moiety. The 2-nitroimidazole moiety undergoes bioreduction by intracellular reduction. In the presence of oxygen, the drug is reoxidized to original state but in hypoxic conditions, the drug undergoes fragmentation and releases the alkylating nitrogen mustard inflicting selective hypoxic cytotoxicity. We studied the redox-cycling behavior of TH-302 using EPR spin trapping with DMPO as the spin trap to monitor the superoxide radical produced during redox cycling of TH-302 when exposed to activating enzymes, in the presence of different concentrations of dissolved oxygen. Using superoxide flux as an orthogonal indicator of DNA alkylating effects of TH-302, we found quantitatively that this process can occur at pO2 levels < 5 mmHg beyond which redox-cycling predominates. The cellular studies evaluating the hypoxic cytotoxicity also were in agreement with the in vitro EPR studies.

TH-302是二元化疗药物，其具有共价连接至DNA烷基化氮芥部分的2-硝基咪唑部分。2-硝基咪唑部分通过细胞内还原进行生物还原。在氧气存在下，药物被再氧化至原始状态，但在缺氧条件下，药物经历片段化并释放烷基化氮芥，造成选择性缺氧细胞毒性。我们研究了TH-302的氧化还原循环行为，使用EPR自旋捕获与DMPO作为自旋陷阱，以监测超氧自由基的TH-302暴露于活化酶时，在不同浓度的溶解氧的存在下，氧化还原循环过程中产生的。使用超氧化物通量作为TH-302的DNA烷基化作用的正交指标，我们定量地发现，这个过程可以发生在pO 2水平5 mmHg，超过该水平，氧化还原循环占主导地位。评价缺氧细胞毒性的细胞研究也与体外EPR研究一致。

项目成果

Brain redox imaging.

• DOI: 10.1007/978-1-61737-992-5_20
• 发表时间: 2011
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Matsumoto K;Hyodo F;Anzai K;Utsumi H;Mitchell JB;Krishna MC
• 通讯作者: Krishna MC

Nitroxides as cancer imaging agents.

氮氧化物作为癌症显像剂。

• DOI: 10.2174/187152011795677526
• 发表时间: 2011
• 期刊: Anti-cancer agents in medicinal chemistry
• 影响因子: 2.8
• 作者: Davis,RyanM;Mitchell,JamesB;Krishna,MuraliC
• 通讯作者: Krishna,MuraliC