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)

在这项诊断试验中，一个含有双特异性非放射性单克隆人源化抗cea（癌胚抗原）单克隆抗体（TF2）和68Ga-或124l标记组胺-丁二酰甘氨酸（HSG-）肽的预靶向系统将用于评估表达cea的局部晚期直肠癌（RC； UICC分期ll/ll）和评估肿瘤对术前放化疗（RT/CT）的反应。我们假设：1。我们将能够建立一个安全的方案，通过免疫pet /CT（免疫正电子发射断层扫描-计算机断层扫描）来可视化和定量表达cea的红细胞。2. 肿瘤摄取与活的肿瘤细胞数量相关；在RT/CT期间和之后，该参数的下降将表明治疗成功。3. 预靶向系统将成为评价晚期cea表达型RC患者在新辅助治疗中的一种有效的新方法。假设1将在研究的第一部分（P1）中被重新评估，我们将评估用124I或68Ga标记肽的最佳条件，并将评估12例表达cea的晚期RC患者单次输注TF2后单次注射124I或68Ga标记的hsg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），从P1期间收集的数据生成的优化方案将用于通过免疫pet评估正在进行的CAO/AIO/ARO-04试验中纳入的晚期RC患者。我们将评估原发肿瘤中存活肿瘤组织的数量三次：(i)在RT/CT之前，（ii）在开始治疗后的第三周内，（iii）在治疗结束后和手术切除肿瘤之前。假设2将通过将个体内肿瘤摄取的相对减少与原发肿瘤的组织病理学回归评分以及其他在其他子项目（主要子项目1,3,5,7）中已被证明可预测肿瘤对新辅助治疗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。

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.