POSITRON EMISSION TOMOGRAPHIC IMAGING OF LUNG TRANSPLANT

肺移植是终末期肺部疾病的首选治疗方法，但肺移植后的存活率仍然令人失望地低。急性排斥反应使肺移植面临更大的风险 失败了。然而，急性排斥反应在临床上通常是沉默的，除了活检之外很难检测到，这需要一个侵入性的程序。因此，检测和量化急性排斥反应的非侵入性方法可能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预后。由于T细胞必须在肺内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[18F]ISO-1，该示踪剂针对增殖标记物Sigma-2受体，最近也被鉴定为孕激素受体膜组分-1(PGRMC1)，以成像肺移植中T细胞的激活。我们已经证明，使用[18F]脱氧葡萄糖([18F]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[18F]ISO-1和[18F]FDG在新的左肺移植小鼠模型和人类肺移植受者中检测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.