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Abstract
PURPOSE:
The study was undertaken to develop and evaluate the potential of an integrin αvβ6-binding peptide (αvβ6-BP) for noninvasive imaging of a diverse range of malignancies with PET.

EXPERIMENTAL DESIGN:
The peptide αvβ6-BP was prepared on solid phase and radiolabeled with 4-[18F]fluorobenzoic acid. In vitro testing included ELISA, serum stability, and cell binding studies using paired αvβ6-expressing and αvβ6-null cell lines. In vivo evaluation (PET/CT, biodistribution, and autoradiography) was performed in a mouse model bearing the same paired αvβ6-expressing and αvβ6-null cell xenografts. A first-in-human PET/CT imaging study was performed in patients with metastatic lung, colon, breast, or pancreatic cancer.

RESULTS:
[18F]αvβ6-BP displayed excellent affinity and selectivity for the integrin αvβ6 in vitro [IC50(αvβ6) = 1.2 nmol/L vs IC50(αvβ3) >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 [18F]αvβ6-BP was rapid, primarily via the kidneys. In patients, [18F]αvβ6-BP was well tolerated without noticeable adverse side effects. PET images showed significant uptake of [18F]αvβ6-BP in both the primary lesion and metastases, including metastasis to brain, bone, liver, and lung.

CONCLUSIONS:
The clinical impact of [18F]αvβ6-BP PET imaging demonstrated in this first-in-human study is immediate for a broad spectrum of malignancies.

Author information

Hausner SH1, Bold RJ2, Cheuy LY3, Chew HK1, Daly ME4, Davis RA1, Foster CC5, Kim EJ1, Sutcliffe JL6,3,7.
1
Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis, Davis and Sacramento, California.
2
Division of Surgical Oncology, Department of Surgery, University of California Davis, Davis and Sacramento, California.
3
Department of Biomedical Engineering, University of California Davis, Davis and Sacramento, California.
4
Department of Radiation Oncology, University of California Davis, Davis and Sacramento, California.
5
Division of Nuclear Medicine, Department of Radiology, University of California Davis, Davis and Sacramento, California.
6
Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis, Davis and Sacramento, California. jlsutcliffe@ucdavis.edu.
7
Center for Molecular and Genomic Imaging, University of California Davis, Davis and Sacramento, California.