Method to evaluate and quantify myocardial injections

描述(由申请人提供)： 直接心肌内注射可能允许局部输送治疗心肌和冠状动脉疾病的蛋白质和基因治疗药物。然而，通过经皮心内膜心肌导管或外科心外膜注射给药的材料的直接命运还知之甚少。注射材料的不明损失可能会对临床前试验的结果产生负面影响。制药开发商和药物输送系统的开发商长期以来都在私下讨论这个问题。最近的一篇文章表明，注射材料的心肌滞留可以有很大的差异。我们假设，可以开发一种商业试剂来在活体模型中提供心脏药物输送系统的检测和定量，并提供在双盲动物试验中唯一识别实验亚群的手段。此外，该试剂可作为一种教学工具，也可作为临床医生在心肌注射技术方面的认证手段。我们的第一阶段申请寻求支持，以开发一套试剂，共同标记稳定的同位素和荧光标记。我们建议的试剂将允许验证心脏注射方法，允许在临床前试验期间监测技术能力，允许识别受试者组，并确保更高质量的体内数据。

DESCRIPTION (provided by applicant): Direct intra myocardial injection may permit local delivery of protein and gene therapy agents for myocardial and coronary artery disease. However, little is known about the immediate fate of materials administered via percutaneous endomyocardial catheters or via surgical epicardial injection. Unrecognized loss of injected material can negatively influence the outcome of a preclinical trial. Both pharmaceutical developers have long privately discussed this problem and developers of drug delivery systems. A recent publication demonstrates that myocardial retention of injected material can vary greatly. We hypothesize that a commercial reagent can be developed to provide both detection and quantitation of cardiac drug delivery systems in vivo models, as well as provide the means to uniquely identify experimental subgroups during double blind animal trials. In addition, this reagent can be used as a teaching tool and as a means to certify clinicians in myocardial injection techniques. Our Phase I application seeks support to develop a set of reagents, co-labeled with both a stable isotope and a fluorescent marker. Our proposed reagent will allow validation of cardiac injection methods, allow monitoring of technical competence during preclinical trails, allow identification of subject groups, and assure higher quality of in vivo data.