PT  - JOURNAL ARTICLE
AU  - Guo, Rong
AU  - Weng, Dinghu
AU  - Xu, Haibo
AU  - Jiang, Dawei
AU  - An, Rui
TI  - <strong>A novel peptide-based 68Ga-PET radiotracer for TIGIT expression visualization</strong>
DP  - 2022 Aug 01
TA  - Journal of Nuclear Medicine
PG  - 2875--2875
VI  - 63
IP  - supplement 2
4099  - http://jnm.snmjournals.org/content/63/supplement_2/2875.short
4100  - http://jnm.snmjournals.org/content/63/supplement_2/2875.full
SO  - J Nucl Med2022 Aug 01; 63
AB  - 2875 Introduction: Accumulating studies have demonstrated that the novel immune checkpoint receptor T cell Ig and ITIM domain (TIGIT) is a promising candidate in cancer immune checkpoint blockade therapy. Elevated TIGIT expression in the tumor microenvironment correlates with improved therapeutic response to anti-TIGIT therapies in preclinical studies. As such, a noninvasive method to quantify TIGIT expression in tumors is crucial to predict the therapeutic effect. In this study, we report a peptide-based positron emission tomography (PET) imaging agent, 68Ga-DOTA-DTBP-3, to visualize TIGIT expression in BALB/c mice bearing 4T1 breast cancer. Methods: DTBP-3, a 12 amino acids D-peptide, is radiolabeled with 68Ga through DOTA conjugation. To assess the affinity of DTBP-3 to TIGIT, a microscale thermophoresis binding assay was performed. Diagnostic value of 68Ga-DOTA-DTBP-3 was further evaluated via stability assay in vitro, animal microPET/CT imaging, biodistribution study, autoradiography, and immunohistochemical staining using 4T1 tumor-bearing BALB/c mice and tissues of interest. For the blocking group, mice were pretreated with one dose of the 400-fold excessive amount of DTBP-3 at 1 h before tracer administration. Results: 68Ga-DOTA-DTBP-3 was synthesized with a radiochemical purity of 97.29 ± 0.59% after purification, and the retention time was 13.4 min as identified by radio-HPLC. 68Ga-DOTA-DTBP-3 was maintained stably in PBS for 1 h at room temperature with a radiochemical purity of 94.39 ± 0.47%. The binding assay revealed a Kd value of 4.1 μM, indicating a high affinity of the tracer to TIGIT. MicroPET/CT imaging, biodistribution, autoradiography, and immunohistochemical staining studies demonstrated that 68Ga-DOTA-DTBP-3 could specifically target TIGIT and delineate 4T1 tumors. Biodistribution studies showed the tumor uptake of 1.10 ± 0.19 %ID/g at 0.5 h post-injection, whereas the tumor uptake in the blocking group was 0.58 ± 0.11 %ID/g, consistent with the in vivo PET imaging results.Conclusions: 68Ga-DOTA-DTBP-3 has great potential for detecting the expression of TIGIT, evaluating the therapeutic effect, and optimizing the prescription of TIGIT checkpoint blockade therapy. It may become a candidate for facilitating the screening of patients and may benefit future clinical practice. Acknowledgments: This work was financially supported by the “Fundamental Research Funds for the Central Universities” (Grant NO. 2042018kf0179).