FDG PET in cancer-associated venothromboembolic disease

描述(由申请人提供)：血栓形成、炎症和癌症之间的联系很强。癌症使患者容易发生血栓，这可能会使治疗复杂化，并且比非癌症患者有更高的发病率和死亡风险。反之亦然，近50%的无缘无故发展为静脉血栓栓塞症(VTE)的患者患有隐匿性癌症，但在这些患者中寻找癌症并不被认为是标准做法。当血凝块位于腹部或盆腔，和/或患者有含碘造影剂时，血凝块形成的诊断就会受到影响。在癌症患者中，与癌症或其治疗相关的多种解剖异常，以及腹部或盆腔血栓倾向的增加，可能会使VTE的诊断进一步复杂化。此外，目前还不存在识别癌症相关血栓形成风险特别高的患者的方法，这是血栓预防的关键步骤。血栓、癌症和炎症之间的联系可能是由于宿主对癌症的反应，导致局部和全身炎症细胞因子和组织因子的表达，这些细胞因子和组织因子作用于血小板和髓系白细胞，产生一系列事件，最终导致血栓形成。FDG PET成像已成为恶性肿瘤诊断、分期和疗效评估的有力工具。根据初步数据和个人观察，我们推测FDGPET在诊断复杂的VTE病例、识别存在隐匿性恶性肿瘤的无缘无故VTE患者以及识别使许多癌症患者易患VTE的全身状态方面可能是有用的辅助手段。该项目的具体目标将在人体受试者身上测试这些假设，并从桌面到床边进行测试。体外研究通过表征FDG摄取、血栓前细胞的激活以及这些细胞表达已知的血栓前基因产物和效应物之间的关系，完成了分子成像循环。

DESCRIPTION (provided by applicant): The association between blood clot formation, inflammation and cancer is strong. Cancer predisposes patients to the development of blood clots, which may complicate therapy and has a higher risk of morbidity and death than in non-cancer patients. The converse is also true, nearly 50% of patients who develop unprovoked venothromboembolic disease (VTE) harbor an occult cancer, yet a search for cancer in these patients is not considered standard of practice. The diagnosis of blood clot formation is compromised when the clot is in the abdomen or pelvis, and/or the patient has a containdication to iodinated contrast. In cancer patients, multiple anatomic abnormalities associated with the cancer or its treatment, and a heightened propensity for intraabdominal or pelvic clot may further complicate the diagnosis of VTE. Further, no current methods exist to identify patients at particularly high risk for cancer-related thrombosis, a critical step in thrombo-prevention. The link between clot, cancer and inflammation may be due to a host response to cancer resulting in expression of both local and systemic inflammatory cytokines and tissue factors that act on platelets and myeloid leukocytes to produce a cascade of events culminating in blood clot formation. FDG PET imaging has emerged as a powerful tool in the diagnosis, staging, and therapeutic assessment of malignancy. Based on preliminary data and personal observation, we hypothesize that FDG PET may be a useful adjunct in the diagnosis of complicated cases of VTE, in identifying patients with unprovoked VTE that harbor an occult malignancy, and in identifying the systemic state that predisposes many cancer patients to VTE. The specific aims of this project will test these hypotheses in human subjects and also span from benchtop to bedside. In vitro studies complete the molecular imaging loop, by characterizing the relationship between FDG uptake, activation of prothrombotic cells, and expression of known prothrombotic gene products and effectors by these cells.