FDG PET in cancer-associated venothromboembolic disease

描述（由申请人提供）：血凝块形成、炎症和癌症之间的联系很强。癌症使患者容易形成血栓，这可能使治疗复杂化，并且比非癌症患者有更高的发病和死亡风险。反之亦然，近50%的非诱发性静脉血栓栓塞性疾病（VTE）患者患有隐匿性癌症，但对这些患者进行癌症检查并不被认为是标准做法。当血凝块位于腹部或骨盆和/或患者有碘造影剂禁忌症时，血栓形成的诊断会受到损害。在癌症患者中，与癌症或其治疗相关的多种解剖异常，以及腹内或盆腔血栓的增加倾向可能进一步使静脉血栓栓塞的诊断复杂化。此外，目前还没有方法来识别癌症相关血栓形成风险特别高的患者，这是预防血栓形成的关键步骤。血块、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，最终形成血块。FDG PET成像已成为恶性肿瘤诊断、分期和治疗评估的有力工具。根据初步数据和个人观察，我们假设FDG PET可能是诊断复杂静脉血栓栓塞病例的有用辅助手段，可用于识别隐匿恶性肿瘤的非诱发性静脉血栓栓塞患者，以及识别易导致许多癌症患者发生静脉血栓栓塞的全身状态。该项目的具体目标将在人类受试者中测试这些假设，并从台式到床边进行测试。体外研究通过表征FDG摄取、血栓形成前细胞的激活以及这些细胞表达已知血栓形成前基因产物和效应物之间的关系，完成了分子成像环。

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.