| Autor: |
Sven H, Hausner, Richard J, Bold, Lina Y, Cheuy, Helen K, Chew, Megan E, Daly, Ryan A, Davis, Cameron C, Foster, Edward J, Kim, Julie L, Sutcliffe |
| Rok vydání: |
2018 |
| Předmět: |
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| Zdroj: |
Clinical cancer research : an official journal of the American Association for Cancer Research. 25(4) |
| ISSN: |
1557-3265 |
| Popis: |
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 positron emission tomography (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 a 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 in vitro (IC(50)(α(v)β(6)) = 1.2 nM vsIC(50)(α β(3)) >10 μM) 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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