68 Ga-Labeled Cystine Knot Peptide Targeting Integrin α v β 6 for Lung Cancer PET Imaging.

Integrin α v β 6 has been considered as a promising biomarker for lung cancer, and its expression is often related to poor prognosis. An α v β 6 -binding cystine knot peptide R 0 1-MG was previously engineered and validated. Here, we developed a positron emission tomography (PET) probe of R 0 1-MG for imaging α v β 6 -positive lung cancer. Cystine knot peptide R 0 1-MG was synthesized through solid-phase peptide synthesis chemistry and radiolabeled with 68 Ga after being conjugated with 1,4,7,10-tetraazacyclododecane- N , N ', N ″, N ‴-tetraacetic acid (DOTA). The stability of 68 Ga-DOTA-R 0 1-MG was analyzed in phosphate-buffered saline (PBS) (pH 7.4) and fetal bovine serum (FBS). The cell uptake assay of the probe was evaluated using α v β 6 -positive (A549 and H1975) and α v β 6 -negative (H1299) lung cancer cell lines. In addition, small animal PET imaging and biodistribution studies of 68 Ga-DOTA-R 0 1-MG were performed in α v β 6 -positive and α v β 6 -negative lung cancer models. Our study showed that 68 Ga-DOTA-R 0 1-MG exhibited excellent stability in PBS and FBS. Small animal PET imaging and biodistribution data revealed that 68 Ga-DOTA-R 0 1-MG displayed rapid and good tumor uptake in animal models with α v β 6 -positive lung cancer, and the probe was rapidly cleared from the normal tissues, resulting in good tumor-to-normal tissue contrasts. Meanwhile, no obvious tumor uptake of 68 Ga-DOTA-R 0 1-MG was observed in animal models with α v β 6 -negative lung cancer, demonstrating specific binding of the probe to integrin α v β 6 . In conclusion, 68 Ga-DOTA-R 0 1-MG has great potential to be a promising PET tracer for imaging α v β 6 -positive lung cancer.