One of the great challenges of oncology is to improve methods for early tumor detection. Thus tumor cell-targeted optical imaging has been intensively studied. Bioimaging with upconversion (UC) phosphors (UCPs) is of considerable interest due to a variety of possible applications taking advantage of infrared-to-visible luminescence. Here we report for the first time tumor cell-targeted UC imaging using UCPs modified with cyclic RGD peptide (RGD-Y2O3). Cyclic RGD peptide binds specifically to integrin alpha(nu)beta(3) which is highly expressed in a tumor cell surface of certain cancer types but not in normal tissues. Since UC emission from RGD-Y2O3 was observed for U87MG cancer cell (high integrin alpha(nu)beta(3) expression), but not for MCF-7 cancer cell (low integrin alpha(nu)beta(3) expression), this UC imaging is considered to be integrin alpha(nu)beta(3) specific. The non-invasive imaging of integrin alpha(nu)beta(3) expression using UCP-based probes will have great potential in cancer imaging in general in living subjects. (C) 2009 Elsevier Inc. All rights reserved.