Peptide-based PET imaging agent of tumor TIGIT expression
Dinghu Weng, Rong Guo, Ziyang Zhu, Yu Gao, Rui An, Xiuman Zhou
Abstract
Abstract 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.