Peptide-based PET imaging agent of tumor TIGIT expression

Autor: Dinghu Weng, Rong Guo, Ziyang Zhu, Yu Gao, Rui An, Xiuman Zhou
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: EJNMMI Research, Vol 13, Iss 1, Pp 1-8 (2023)
Druh dokumentu: article
ISSN: 2191-219X
DOI: 10.1186/s13550-023-00982-7
Popis: 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, 68Ga-DOTA-DTBP-3, was developed to non-invasively detect TIGIT expression by micro-PET in tumor-bearing BALB/c mice. DTBP-3, a D-peptide comprising of 12 amino acids, was radiolabeled with 68Ga through a DOTA chelator. In vitro studies were performed to evaluate the affinity of 68Ga-DOTA-DTBP-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 68Ga-DOTA-DTBP-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 68Ga-DOTA-DTBP-3 could be specifically targeted in 4T1 tumor-bearing mice, with a highest uptake at 0.5 h. Conclusion 68Ga-DOTA-DTBP-3 holds potential for non-invasively detect tumor TIGIT expression and for timely assessment of the therapeutic effect of immune checkpoint blockade.
Databáze: Directory of Open Access Journals
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