Peptide-based PET imaging agent of tumor TIGIT expression

BACKGROUND: Accumulating studies have demonstrated that elevated TIGIT expression in tumor microenvironment correlates with better therapeutic response to TIGIT-based immunotherapy in pre-clinical studies. Therefore, a non-invasive method to detect tumor TIGIT expression is crucial to predict the therapeutic effect. METHODS: In this study, a peptide-based PET imaging agent, (68)Ga-DOTA-(D)TBP-3, was developed to non-invasively detect TIGIT expression by micro-PET in tumor-bearing BALB/c mice. (D)TBP-3, a D-peptide comprising of 12 amino acids, was radiolabeled with (68)Ga through a DOTA chelator. In vitro studies were performed to evaluate the affinity of (68)Ga-DOTA-(D)TBP-3 to TIGIT and its stability in fetal bovine serum. In vivo studies were assessed by micro-PET, biodistribution, and immunohistochemistry on tumor-bearing BALB/c mice. RESULTS: The in vitro studies showed the equilibrium dissociation constant of (68)Ga-DOTA-(D)TBP-3 for TIGIT was 84.21 nM and its radiochemistry purity was 89.24 ± 1.82% in FBS at 4 h in room temperature. The results of micro-PET, biodistribution and immunohistochemistry studies indicated that (68)Ga-DOTA-(D)TBP-3 could be specifically targeted in 4T1 tumor-bearing mice, with a highest uptake at 0.5 h. CONCLUSION: (68)Ga-DOTA-(D)TBP-3 holds potential for non-invasively detect tumor TIGIT expression and for timely assessment of the therapeutic effect of immune checkpoint blockade.