POSITRON EMISSION TOMOGRAPHIC IMAGING OF LUNG TRANSPLANT

肺移植是治疗终末期肺病的首选方法，但肺移植后的存活率仍然很低。急性排斥反应使肺移植物面临更大的风险， 失败然而，急性排斥反应通常在临床上是沉默的，并且难以通过除活检以外的任何手段检测到，活检需要侵入性操作。因此，检测和量化急性排斥反应的存在的非侵入性方法可以通过提高我们检测需要治疗的急性排斥反应的能力来潜在地改善肺移植受者的结果。由于T细胞必须在肺中增殖才能引起急性排斥反应，我们建议使用新型正电子发射断层扫描（PET）示踪剂[18 F]ISO-1，其靶向增殖标记物sigma-2受体，最近也被表征为孕酮受体膜组分-1（PGRMC 1），以成像肺移植物中的T细胞活化。我们已经证明，[18 F]氟脱氧葡萄糖（[18 F]FDG）的PET成像也可以检测急性排斥反应，并可以测量其对治疗的反应;因此，我们将评估[18 F]ISO-1和[18 F]FDG检测左肺移植新小鼠模型和人肺移植受体急性排斥反应的能力。

Lung transplantation is the treatment of choice for end-stage lung disease, but survival after lung transplant remains disappointingly low. Acute rejection episodes put lung grafts at greater risk of failing. However, acute rejection is often clinically silent and difficult to detect by any means other than biopsy, which requires an invasive procedure. Therefore, noninvasive methods for detecting and quantifying the presence of acute rejection could potentially improve outcomes for lung transplant recipients by improving our ability to detect acute rejection that requires treatment. Because T cells must proliferate in the lungs to cause acute rejection, we propose using the novel positron emission tomography (PET) tracer [18F]ISO-1, which targets the proliferation marker sigma-2 receptor, also recently characterized as the progesterone receptor membrane component-1 (PGRMC1), to image T cell activation in lung grafts. We have shown that PET imaging with [18F]fluorodeoxyglucose ([18F]FDG) also detects acute rejection and can measure its response to treatment; therefore, we will evaluate the ability of [18F]ISO-1 and [18F]FDG to detect acute rejection in a novel mouse model of left lung transplantation and in human lung transplant recipients.