Preclinical Development and First-in-Human Imaging of the Integrin α v β 6 with [ 18 F]α v β 6 -Binding Peptide in Metastatic Carcinoma.

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.
(©2018 American Association for Cancer Research.)