基于PET/MR肿瘤代谢边界指导结直肠癌手术范围的分子影像研究

Colorectal cancer (CRC) is one of the most common malignant tumors. Even after radical surgery, recurrence occur in 35% of CRC patients. Cancer-associated fibroblast (CAF) are the most important components of tumor stroma. Our previous work found that the glucose uptake and lactate accumulation of CAF increased significantly. With matched clinicopathological features, CAF infiltration was observed only in surgically resected margins of high 18F-FDG uptake patients along with a poor prognosis after the same radical surgery. Based on this, we propose that based on the metabolic characteristics of CAF, the complete boundary of the tumor are defined by molecular imaging combined with glucose uptake and lactate concentration. Then we can use this new boundary to guide tumor surgery and radiotherapy. In this study, we planned to define the metabolic boundary of tumors by PET / MR. We perform 18F-FDG PET to detect glucose uptake boundary, synchronously perform MRSI to detect lactate boundary. We aimed to cover the tumor as well as the tumor-promoting stroma. We attempt to verify the benefit of the metabolic boundary for reducing the postoperative recurrence, and provide an effective molecular imaging method to guide the scope of clinical resection of CRC.

结直肠癌是最常见的恶性肿瘤之一，即使经根治性手术，仍有35%的患者出现复发与转移。肿瘤相关成纤维细胞（CAF）为肿瘤间质中最主要的组成成分。我们的前期工作发现CAF细胞葡萄糖摄取显著增加，直接促进肿瘤的FDG摄取和乳酸积聚。在临床病理特征匹配的情况下，经相同根治性手术后，仅在FDG高摄取患者的手术切缘标本中观察到CAF细胞浸润，并且预后不佳。基于此，我们提出根据CAF的代谢特征，通过分子影像检测葡萄糖的摄取和乳酸的浓度来界定肿瘤的完整边界，从而指导肿瘤的手术和放疗。在本研究中，我们将应用一体化PET/MR分子显像技术，通过FDG摄取及同步MRSI乳酸显像双重界定肿瘤的代谢边界，边界范围将涵盖核心肿瘤区及CAF为代表的外围肿瘤区，并探索代谢边界对于减少结直肠癌术后复发的价值，为指导临床手术切除范围以减少肿瘤复发提供有效的分子影像评估手段。

研究背景：结直肠病变的良恶性鉴别是临床难点，特别是18F-FDG PET显像阳性的病灶仍不能确定其良恶性。随着肿瘤间质在肿瘤生物学行为中的研究和认识的增强，新型的分子探针针对肿瘤相关成纤维细胞的FAPI显像在多种肿瘤中显示出明确的临床价值，本研究探索FAPI在肠道病变中的诊断价值。.研究方法：通过AOM/DSS肠炎诱导肠癌模型的建立，进行双分子探针扫描18F-FDG和68Ga-FAPI-04的PET显像。在双分子探针显像临床研究的病例中观察其肠道病变的显示。对18F-FDG阳性的肠道病变进行病理学的分析，免疫组化染色等研究。.研究结果：在双分子探针应用于胃癌新辅助治疗疗效预测的临床研究中，入组的22例患者中有8例显示结直肠区域存在18F-FDG高摄取的病灶，这些病灶在68Ga-FAPI-04PET显像中均为阴性。AOM/DSS模型中，FAP可鉴别FDG阳性的炎症性病灶和肿瘤性病灶。FAP的摄取随肿瘤形成逐渐升高。回顾了本院FDG阳性肠道病变的病理FAP免疫组化，良性病变中FAP的阳性率为20.5%（16/78），恶性病变中的阳性率为85.1%（80/94）。.结论：在AOM/DSS炎症性肠病诱导肠癌模型和临床病例中，68Ga-FAPI-04可较FDG能更好的鉴别肠道病变的良恶性。