DIAGNOSIS OF LEFT VENTRICULAR ASSIST DEVICE INTRAPUMP THROMBOSIS

 描述（由申请人提供）： 在本次重新提交中，申请人建议使用其先前开发的纤维蛋白特异性99 mTc小四聚体分子试剂（99 mTc-F4 A）来定量和表征左心室辅助装置（LVAD）回路中的血栓形成，并将核信号与泵组织病理学结果进行比较。 专家组一致认为，申请人在回应前几位评审员的担忧方面做得很好，包括取消了开发手持设备的目标。 检测VAD中血栓形成的能力是一项未满足的临床需求，具有高度意义，研究者团队被认为非常强大，研究环境被认为良好。 四聚体探针被认为是新颖的，与先前的探针相比具有降低的血浆干扰和改善的亲和力。 该方法在目标内是合乎逻辑的，尽管专家组担心目标的顺序似乎是颠倒的（目标1中的VAD成像和目标2中的探头优化）。 也不清楚摄取是否可检测，特别是在存在减毒介质的情况下。 审评员还对大型动物工作缺乏扫描仪表示关切，因为他们同意需要在大型动物模型中进行成像。 尽管这些担忧削弱了评审人员对该应用的热情，但其意义被认为超过了困难，专家组得出结论，拟议的工作可能对LVAD中血栓形成的早期识别产生很大影响。

 DESCRIPTION (provided by applicant): In this resubmission, the applicants propose to use their previously developed fibrin-specific 99mTc small tetrameric molecule agent (99mTc-F4A) to quantify and characterize thrombus formation in left ventricular assist device (LVAD) circuits and compare the nuclear signal with pump histopathology results. The panel agreed that the applicants did a good job of responding to the concerns of the previous reviewers, including eliminating the aim regarding developing a handheld device. The ability to detect thrombus formation in VAD is an unmet clinical need with high significance, the team of investigators was considered very strong and the research environment was considered good. The tetrameric probe was considered novel, with decreased plasma interference and improved affinity over previous probes. The approach was logical within the aims, although the panel was concerned that the order of Aims seemed backwards (imaging the VAD in Aim 1 and optimizing the probe in Aim 2). It was also not clear if uptake would be detectable, especially in the presence of an attenuating medium. Reviewers also expressed concern regarding lack of access to a scanner for large animal work, because they agreed that imaging in a large animal model was needed. Although these concerns tempered the enthusiasm of the reviewers for this application, the significance was thought to outweigh the difficulties, and the panel concluded that the proposed work could have a high impact on early recognition of thrombus formation in LVADs.