Targeted In vivo Imaging of Integrin αvβ6 with an improved Radiotracer and Its Relevance in a Pancreatic Tumor Model

The cell surface receptor α v β 6 is epithelial specific, and its expression is tightly regulated; it is low or undetectable in adult tissues but has been shown to be increased in many different cancers, including pancreatic, cervical, lung, and colon cancers. Studies have described α v β 6 as a prognostic biomarker linked to poor survival. We have recently shown the feasibility of imaging α v β 6 in vivo by positron emission tomography (PET) using the peptide [ 18 F]FBA-A20FMDV2. Here, we describe improved α v β 6 imaging agents and test their efficacy in a mouse model with endogenous α v β 6 expression. The modified compounds maintained high affinity for α v β 6 and >1,000-fold selectivity over related integrins (by ELISA) and showed significantly improved α v β 6 -dependent binding in cell-based assays (>60% binding versus 18 F]FBA-A20FMDV2). In vivo studies using either a melanoma cell line (transduced α v β 6 expression) or the BxPC-3 human pancreatic carcinoma cell line (endogenous α v β 6 expression) revealed that the modified compounds showed significantly improved tumor retention. This, along with good clearance of nonspecifically bound activity, particularly for the new radiotracer [ 18 F]FBA-PEG 28 -A20FMDV2, resulted in improved PET imaging. Tumor/pancreas and tumor/blood biodistribution ratios of >23:1 and >47:1, respectively, were achieved at 4 hours. Significantly, [ 18 F]FBA-PEG 28 -A20FMDV2 was superior to 2-[ 18 F]fluoro-2-deoxy-d-glucose ([ 18 F]FDG) in imaging the BxPC-3 tumors. Pancreatic ductal adenocarcinoma is highly metastatic and current preoperative evaluation of resectability using noninvasive imaging has limited success, with most patients having metastases at time of surgery. The fact that these tumors express α v β 6 suggests that this probe has significant potential for the in vivo detection of this malignancy, thus having important implications for patient care and therapy. [Cancer Res 2009;69(14):5843–50]