In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 69, No. 14 ( 2009-07-15), p. 5843-5850
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 αvβ6 expression. The modified compounds maintained high affinity for αvβ6 and & gt;1,000-fold selectivity over related integrins (by ELISA) and showed significantly improved αvβ6-dependent binding in cell-based assays ( & gt;60% binding versus & lt;10% for [18F]FBA-A20FMDV2). In vivo studies using either a melanoma cell line (transduced αvβ6 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 & gt;23:1 and & gt;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. [Cancer Res 2009;69(14):5843–50]
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/0008-5472.CAN-08-4410
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2009
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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