Preclinical development and first-in-human imaging of the integrin a v b 6 with [ 18 F]a v b 6 -binding peptide in metastatic carcinoma

Sven H. Hausner, Richard J Bold, Lina Y. Cheuy, Helen K Chew, Megan E Daly, Ryan A. Davis, Cameron C Foster, Edward Kim, Julie Sutcliffe

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Purpose: The study was undertaken to develop and evaluate the potential of an integrin a v b 6 -binding peptide (a v b 6 -BP) for noninvasive imaging of a diverse range of malignancies with PET. Experimental Design: The peptide a v b 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 a v b 6 -expressing and a v b 6 -null cell lines. In vivo evaluation (PET/CT, biodistribution, and autoradiography) was performed in a mouse model bearing the same paired a v b 6 -expressing and a v b 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]a v b 6 -BP displayed excellent affinity and selectivity for the integrin a v b 6 in vitro [IC 50 (a v b 6 ) ¼ 1.2 nmol/L vs IC 50 (a v b 3 ) >10 mmol/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]a v b 6 -BP was rapid, primarily via the kidneys. In patients, [ 18 F]a v b 6 -BP was well tolerated without noticeable adverse side effects. PET images showed significant uptake of [ 18 F]a v b 6 -BP in both the primary lesion and metastases, including metastasis to brain, bone, liver, and lung. Conclusions: The clinical impact of [ 18 F]a v b 6 -BP PET imaging demonstrated in this first-in-human study is immediate for a broad spectrum of malignancies.

Original languageEnglish (US)
Pages (from-to)1206-1215
Number of pages10
JournalClinical Cancer Research
Issue number4
StatePublished - Feb 15 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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