CAREER: Imaging Protease Activity In Vivo with the T2/T1 Signal Quenching Strategy

职业：利用 T2/T1 信号淬灭策略对体内蛋白酶活性进行成像

• 批准号: 0546962
• 负责人: Niren Murthy
• 金额: $ 40万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0546962&HistoricalAwards=false
• 关键词: CAREER; Imaging; Protease; Activity; Vivo

0546962MurthyThe applicant proposes to use the T1/T2 quenching effect for imaging protease activity, and he has demonstrated in preliminary results a combined T2 and T1 agent (Dysprosium and Gadolinium connected by a PEG chain) which has very small modulation to the MR signal intensity, due to the offsetting effect of the T2 and T1 agents. By design, the T2 agent is attached to the PEG chain through a trypsin cleavage site, which can be broken by a target enzyme (e.g. trypsin). Once detached from the PEG chain, the T2 agent loses its modulation effect on the MR signal, resulting in an intensity increase reflecting the protease activity. The applicant ultimately seeks to apply this methodology to image the activity of MMP-7 in mouse tumors, since it is over-expressed in several cancers.

0546962Murthy申请人提出使用T1/T2猝灭效应对蛋白酶活性进行成像，并且他在初步结果中证明了组合的T2和T1试剂（通过PEG链连接的镝和钆），由于T2和T1试剂的抵消效应，其对MR信号强度的调节非常小。根据设计，T2 试剂通过胰蛋白酶切割位点连接到 PEG 链，该切割位点可以被目标酶（例如胰蛋白酶）断裂。一旦与 PEG 链分离，T2 试剂就会失去对 MR 信号的调节作用，导致反映蛋白酶活性的强度增加。申请人最终寻求应用这种方法来对小鼠肿瘤中 MMP-7 的活性进行成像，因为它在几种癌症中过度表达。