Preclinical Development and First-in-Human Imaging of the Integrin αβ with [F]αβ-Binding Peptide in Metastatic Carcinoma.

Purpose: The study was undertaken to develop and evaluate the potential of an integrin αβ-binding peptide (αβ-BP) for noninvasive imaging of a diverse range of malignancies with PET.

Experimental Design: The peptide αβ-BP was prepared on solid phase and radiolabeled with 4-[F]fluorobenzoic acid. testing included ELISA, serum stability, and cell binding studies using paired αβ-expressing and αβ-null cell lines. evaluation (PET/CT, biodistribution, and autoradiography) was performed in a mouse model bearing the same paired αβ-expressing and αβ-null cell xenografts. A first-in-human PET/CT imaging study was performed in patients with metastatic lung, colon, breast, or pancreatic cancer.

Results: [F]αβ-BP displayed excellent affinity and selectivity for the integrin αβ [IC(αβ) = 1.2 nmol/L IC(αβ) >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 [F]αβ-BP was rapid, primarily via the kidneys. In patients, [F]αβ-BP was well tolerated without noticeable adverse side effects. PET images showed significant uptake of [F]αβ-BP in both the primary lesion and metastases, including metastasis to brain, bone, liver, and lung.

Conclusions: The clinical impact of [F]αβ-BP PET imaging demonstrated in this first-in-human study is immediate for a broad spectrum of malignancies.