High-resolution in vivo imaging of breast cancer by targeting the pro-invasive integrin alphavbeta6.
The integrin alphavbeta6 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, alphavbeta6 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 alphavbeta6. Using a newly generated pair of isogenic human cell lines that differ only in alphavbeta6 expression, it was shown, using biodistribution and SPECT imaging, that indium-111-labelled A20FMDV2 locates specifically to alphavbeta6-expressing tissues in vivo, achieving at least seven-times higher retention in alphavbeta6-positive than in alphavbeta6-negative tumours. In further studies with MCF10.DCIS.COM and MCF10A.CA1a breast carcinoma cell lines, which express alphavbeta6 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 alphavbeta6 for imaging in vivo the often more aggressive, alphavbeta6-positive cancers. In the future, A20FMDV2 could serve also to deliver therapy to these same cancers.
Saha
Antonio
A
Centre for Tumour Biology, Queen Mary University of London, Barts and London School of Medicine & Dentistry, Institute of Cancer and CR-UK Clinical Centre, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
Ellison
David
D
Thomas
Gareth J
GJ
Vallath
Sabarinath
S
Mather
Stephen J
SJ
Hart
Ian R
IR
Marshall
John F
JF
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics; D016023:Integrins / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D004369:Pentetic Acid / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000378:metabolism / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D007205:Indium Radioisotopes; D016023:Integrins; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; C073878:integrin alphavbeta6; D004369:Pentetic Acid