TY - JOUR
T1 - Use of a peptide derived from foot-and-mouth disease virus for the noninvasive imaging of human cancer
T2 - Generation and evaluation of 4-[ 18F]fluorobenzoyl A20FMDV2 for in vivo imaging of integrin αvβ6 expression with positron emission tomography
AU - Hausner, Sven H.
AU - DiCara, Danielle
AU - Marik, Jan
AU - Marshall, John F.
AU - Sutcliffe, Julie
PY - 2007/8/15
Y1 - 2007/8/15
N2 - Expression of the epithelial-specific integrin αvβ 6 is low or undetectable in most adult tissues but may be increased during wound healing and inflammation and is up-regulated dramatically by many different carcinomas, making αvβ6 a promising target for the in vivo detection of cancer using noninvasive imaging. In addition, αvβ6 is recognized as promoting invasion and correlates with aggressive behavior of human cancers and thus agents that recognize αvβ6 specifically in vivo will be an essential tool for the future management of α vβ6-positive cancers. Recently, we identified the peptide NAVPNLRGDLQV-LAQKVART (A20FMDV2), derived from foot-and-mouth disease virus, as a potent inhibitor of αvβ6. Using flow cytometry and ELISA, we show that this peptide is highly selective, inhibiting αvβ6-ligand binding with a IC 50 of 3 nmol/L, an activity 1,000-fold more selective for αvβ6 than for other RGD-directed integrins (αvβ3, αvβ5, and α5β1). A20FMDV2 was radiolabeled on solid-phase using 4-[18F]fluorobenzoic acid, injected into mice bearing both αvβ6-negative and αvβ6-positive (DX3puro/DX3puroβ6 cell lines) xenografts and imaged using a small animal positron emission tomography (PET) scanner. Rapid uptake (<30 min) and selective retention (>5 h) of radioactivity in the αvβ6-positive versus the αvβ6-negative tumor, together with fast renal elimination of nonspecifically bound activity, resulted in specific imaging of the αvβ6-positive neoplasm. These data suggest that PET imaging of αvβ6-positive tumors is feasible and will provide an important new tool for early detection and improved management of many types of cancers.
AB - Expression of the epithelial-specific integrin αvβ 6 is low or undetectable in most adult tissues but may be increased during wound healing and inflammation and is up-regulated dramatically by many different carcinomas, making αvβ6 a promising target for the in vivo detection of cancer using noninvasive imaging. In addition, αvβ6 is recognized as promoting invasion and correlates with aggressive behavior of human cancers and thus agents that recognize αvβ6 specifically in vivo will be an essential tool for the future management of α vβ6-positive cancers. Recently, we identified the peptide NAVPNLRGDLQV-LAQKVART (A20FMDV2), derived from foot-and-mouth disease virus, as a potent inhibitor of αvβ6. Using flow cytometry and ELISA, we show that this peptide is highly selective, inhibiting αvβ6-ligand binding with a IC 50 of 3 nmol/L, an activity 1,000-fold more selective for αvβ6 than for other RGD-directed integrins (αvβ3, αvβ5, and α5β1). A20FMDV2 was radiolabeled on solid-phase using 4-[18F]fluorobenzoic acid, injected into mice bearing both αvβ6-negative and αvβ6-positive (DX3puro/DX3puroβ6 cell lines) xenografts and imaged using a small animal positron emission tomography (PET) scanner. Rapid uptake (<30 min) and selective retention (>5 h) of radioactivity in the αvβ6-positive versus the αvβ6-negative tumor, together with fast renal elimination of nonspecifically bound activity, resulted in specific imaging of the αvβ6-positive neoplasm. These data suggest that PET imaging of αvβ6-positive tumors is feasible and will provide an important new tool for early detection and improved management of many types of cancers.
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U2 - 10.1158/0008-5472.CAN-07-1026
DO - 10.1158/0008-5472.CAN-07-1026
M3 - Article
C2 - 17699789
AN - SCOPUS:34548007871
VL - 67
SP - 7833
EP - 7840
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 16
ER -