Immuno-PET/CT analyses for prediction of tumor response induced by preoperative chemoradiotherapy (RT/CT) in locally advanced rectal cancer (RC; UICC stages II/III)

免疫 PET/CT 分析用于预测局部晚期直肠癌（RC；UICC II/III 期）术前放化疗 (RT/CT) 诱导的肿瘤反应

• 批准号: 50705160
• 负责人: Professor Dr. Johannes Meller
• 金额: --
• 依托单位: Klinik für Allgemein-, Viszeral- und Kinderchirurgie
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/50705160?language=en
• 关键词: Immuno; PET; CT; analyses; prediction

In this diagnostic trial, a pretargeting system with a bispecific nonradioactive monoclonal humanized anti-CEA (carcinoembryonic antigen) monoclonal antibody (mAb) (TF2) and a 68Ga- or 124l-labeled histamine-succinyl-glycine (HSG-) peptide will be used in evaluating CEA-expressing locally advanced rectal cancer (RC; UICC stages ll/lll) and in assessing tumor response to preoperative chemoradiotherapy (RT/CT). We hypothesize that: 1. We will be able to establish a safe protocol for visualizing and quantifying CEA-expressing RCs by means of immuno-PET/CT (immuno-positron emission tomography-computed tomography). 2. Tumor uptake will correlate with the amount of viable tumor cells; a decrease in this parameter during and after RT/CT will indicate therapeutic success. 3. The pretargeting system will be an efficient new method in evaluating patients with advanced CEA-expressing RC in a neoadjuvant setting. Hypothesis 1 will be reassessed during the first part (P1) of the study, where we will evaluate optimal conditions for labeling the peptide with either 124I- or 68Ga and will assess the safety, pharmacokinetics, and tumor targeting of a single infusion of TF2 followed by a single injection of a 124I- or 68Ga-labeled HSG-peptide in 12 patients with CEA-expressing advanced RC. During the second part (P2) of the study, an optimized protocol generated from the data collected during P1 will be used for evaluating patients with advanced RC included in the ongoing CAO/AIO/ARO-04 trial by means of immuno-PET. We will evaluate the amount of viable tumor tissue in the primary tumor three times: (i) before RT/CT, (ii) within the third week after starting the therapy, and (iii) after the end of therapy and immediately before surgical resection of the tumor. Hypothesis 2 will be assessed by correlating the relatively intraindividual decrease of tumor uptake with the histopathological regression score of the primary tumor and other molecular and clinical parameters that have been shown to predict tumor response to neoadjuvant therapy in the other subprojects (mainly subprojects 1, 3, 5, 7). Hypothesis 3 will be reassessed by the correlation of the preoperative and postoperative UICC status determined by immuno-PET/CT with the preoperative and postoperative UICC status determined by other approved methods and by histology.

在这项诊断试验中，使用双功能非放射性人源化抗癌胚抗原(CEA)单抗(TF2)和68Ga或1241标记的组胺琥珀酰甘氨酸(HSG-)肽的预靶向系统将用于评估CEA表达的局部进展期直肠癌(RC；UICC分期11/11)和肿瘤对术前放化疗(RT/CT)的反应。我们的假设是：1.我们将能够建立一种安全的方法，通过免疫-PET/CT(免疫-正电子发射断层扫描-计算机断层扫描)来可视化和定量检测CEA表达的RCS。2.肿瘤摄取将与活肿瘤细胞的数量相关；在RT/CT期间和之后，这一参数的下降将预示治疗的成功。3.预靶向系统将成为在新辅助环境下评估晚期CEA表达RC患者的一种有效的新方法。假设1将在研究的第一部分(P1)重新评估，我们将评估用124I或68Ga标记多肽的最佳条件，并将评估在12名CEA表达的晚期RC患者中单次注射TF2后单次注射124I或68Ga标记的HSG多肽的安全性、药代动力学和肿瘤靶向性。在研究的第二部分(P2)，根据在P1期间收集的数据生成的优化方案将用于通过免疫-PET的方式评估正在进行的CAO/AIO/ARO-04试验中的晚期RC患者。我们将评估原发肿瘤中存活的肿瘤组织数量三次：(I)在RT/CT之前，(Ii)在开始治疗后的第三周内，以及(Iii)在治疗结束后和紧接肿瘤手术切除之前。假设2将通过在其他子项目(主要是子项目1、3、5、7)中将肿瘤摄取的相对个体内减少与原发肿瘤的组织病理学回归分数以及其他已被证明可预测肿瘤对新辅助治疗的反应的分子和临床参数相关联来评估。假设3将通过免疫-PET/CT确定的术前和术后UICC状态与由其他批准的方法和组织学确定的术前和术后UICC状态的相关性来重新评估。