High-resolution in vivo imaging of breast cancer by targeting the pro-invasive integrin alphavbeta6

Abstract

The integrin αvβ6 is expressed only on epithelia and then usually only during processes of tissue remodelling including cancer, where its high expression correlates with reduced survival. Thus, αvβ6 represents an important target for imaging and therapy of cancer and new molecular-specific targeting agents are required. We have developed A20FMDV2, a peptide derived from the VP1 coat protein of foot-and-mouth-disease virus that binds specifically and stably to αvβ6. Using a newly generated pair of isogenic human cell lines that differ only in αvβ6 expression, it was shown, using biodistribution and SPECT imaging, that indium-111-labelled A20FMDV2 locates specifically to αvβ6-expressing tissues in vivo, achieving at least seven-times higher retention in αvβ6-positive than in αvβ6-negative tumours. In further studies with MCF10.DCIS.COM and MCF10A.CA1a breast carcinoma cell lines, which express αvβ6 endogenously, the radiopeptide achieved similar levels of tumour retention and permitted excellent discriminatory imaging of tumours. Thus, A20FMDV2 can be used for molecular-specific targeting of αvβ6 for imaging in vivo the often more aggressive, αvβ6-positive cancers. In the future, A20FMDV2 could serve also to deliver therapy to these same cancers.

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