Targeted in vivo imaging of integrin αvβ6 with an improved radiotracer and its relevance in a pancreatic tumor model

Sven H. Hausner, Craig K. Abbey, Richard J Bold, M. Karen Gagnon, Jan Marik, John F. Marshall, Cathy E. Stanecki, Julie Sutcliffe

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

The cell surface receptor αvβ6 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 αvβ6 as a prognostic biomarker linked to poor survival. We have recently shown the feasibility of imaging αvβ6 in vivo by positron emission tomography (PET) using the peptide [18F]FBA-A20FMDV2. Here, we describe improved αvβ6 imaging agents and test their efficacy in a mouse model with endogenous αvβ 6 expression. The modified compounds maintained high affinity for αvβ6 and >1,000-fold selectivity over related integrins (by ELISA) and showed significantly improved αvβ6-dependent binding in cell-based assays (>60% binding versus <10% for [18F]FBA-A20FMDV2). In vivo studies using either a melanoma cell line (transduced αvβ 6 expression) or the BxPC-3 human pancreatic carcinoma cell line (endogenous αvβ6 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 [18F]FBA-PEG28-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, [ 18F]FBA-PEG28-A20FMDV2 was superior to 2-[ 18F]fluoro-2-deoxy-D-glucose ([18F]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 αvβ6 suggests that this probe has significant potential for the in vivo detection of this malignancy, thus having important implications for patient care and therapy.

Original languageEnglish (US)
Pages (from-to)5843-5850
Number of pages8
JournalCancer Research
Volume69
Issue number14
DOIs
StatePublished - Jul 15 2009

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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