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是一种二元化学治疗药物，其2-硝基咪唑部分与DNA烷基氮芥末部分共价关联。 2-硝基咪唑部分通过细胞内还原进行生物补充。在存在氧气的情况下，该药物被重新氧化为原始状态，但在低氧条件下，该药物会经历碎片化并释放出烷基化的氮芥末，从而造成选择性的低氧细胞毒性。我们使用EPR自旋捕获与DMPO一起研究了TH-302的氧化还原循环行为，作为自旋陷阱，以监测在不同浓度的溶解氧气的情况下，在暴露于激活酶的情况下，在TH-302的氧化还原循环期间产生的超氧化物自由基。使用超氧化通量作为TH-302的DNA烷基化作用的正交指标，我们定量地发现，该过程可以在PO2水平<5 mmHg的水平<5 mmHg下发生，氧化还原循环占主导地位。评估低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