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

申请人提出使用T1/T2猝灭效应来成像蛋白酶活性，并且他已经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信号强度具有非常小的调节。通过设计，T2试剂通过胰蛋白酶切割位点与PEG链连接，该位点可被靶酶（例如胰蛋白酶）破坏。一旦与PEG链分离，T2试剂就失去其对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该方法来成像小鼠肿瘤中MMP-7的活性，因为它在几种癌症中过表达。

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.