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)

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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.