Imaging of the secreted extracellular periostin, an important marker of invasion in tumor microenvironment in esophageal cancer

Periostin, an extracellular matrix protein, plays key role in cell adhesion and motility within the tumor microenvironment, and is correlated with tumor invasion. We developed and characterized a PET tracer that specifically targets periostin, and evaluated the probe in preclinical models of esophageal squamous cell carcinoma (ESCC).
METHODS: The Institutional Animal Care and Use Committee approved all animal studies. Anti-periostin-F(ab')2 was generated from a monoclonal antibody by enzymatic digestion, conjugated to DOTA and labeled with 64Cu. Human ESCC cell lines, TE-11 with high and TT with minimal periostin expression, were implanted in nu/nu mice to generate the positive and control tumor models, respectively. PET/CT imaging was performed at 6, 12, and 24 hours and organ specific biodistribution at 24 hours after probe injection. Additionally the probe was tested in a genetically engineered mouse model (GEMM) of periostin-expressing distal esophageal/forestomach ESCC. Tissue microarrays of esophageal neoplasms and ESCC as well as extracted tumor samples were stained for periostin.
RESULTS: We generated a 64Cu-DOTA-anti- periostin-F(ab')2 with dissociation constant of 29.2 ± 3.0 nM. PET/CT images and biodistribution studies showed significantly higher tracer uptake in TE-11 compared to TT tumors (SUVmax-24h: 0.67±0.09 vs. 0.36±0.03, p CONCLUSION: We demonstrated that specific imaging of ECM periostin in ESCC is feasible using a targeted PET tracer. Detection of periostin in the tumor microenvironment may help with early detection, post-surgical follow up, and with in situ characterization of primary and metastatic lesions.