Abstract
PURPOSE: The study was undertaken to develop and evaluate the potential of an integrin α(v)β(6)-binding peptide (α(v)β(6)-BP) for noninvasive imaging of a diverse range of malignancies with PET. EXPERIMENTAL DESIGN: The peptide α(v)β(6)-BP was prepared on solid phase and radiolabeled with 4-[(18)F]fluorobenzoic acid. In vitro testing included ELISA, serum stability, and cell binding studies using paired α(v)β(6)-expressing and α(v)β(6)-null cell lines. In vivo evaluation (PET/CT, biodistribution, and autoradiography) was performed in a mouse model bearing the same paired α(v)β(6)-expressing and α(v)β(6)-null cell xenografts. A first-in-human PET/CT imaging study was performed in patients with metastatic lung, colon, breast, or pancreatic cancer. RESULTS: [(18)F]α(v)β(6)-BP displayed excellent affinity and selectivity for the integrin α(v)β(6) in vitro [IC(50)(α(v)β(6)) = 1.2 nmol/L vs IC(50)(α(v)β(3)) >10 μmol/L] in addition to rapid target-specific cell binding and internalization (72.5% ± 0.9% binding and 52.5% ± 1.8%, respectively). Favorable tumor affinity and selectivity were retained in the mouse model and excretion of unbound [(18)F]α(v)β(6)-BP was rapid, primarily via the kidneys. In patients, [(18)F]α(v)β(6)-BP was well tolerated without noticeable adverse side effects. PET images showed significant uptake of [(18)F]α(v)β(6)-BP in both the primary lesion and metastases, including metastasis to brain, bone, liver, and lung. CONCLUSIONS: The clinical impact of [(18)F]α(v)β(6)-BP PET imaging demonstrated in this first-in-human study is immediate for a broad spectrum of malignancies.