Dataset Information

Preclinical and exploratory human studies of novel ⁶⁸Ga-labeled D-peptide antagonist for PET imaging of TIGIT expression in cancers.

ABSTRACT:

Purpose

While TIGIT has been propelled as a next-generation target in cancer immunotherapy, anti-TIGIT therapy seems to be promising for a fraction of patients in clinical trials. Therefore, patient stratification is critical for this therapy, which could benefit from a whole-body, non-invasive, and quantitative evaluation of TIGIT expression in cancers. In this study, a ⁶⁸Ga-labeled D-peptide antagonist, ⁶⁸Ga-GP12, was developed and validated for PET imaging of TIGIT expression in vitro, in vivo, and in an exploratory human study.

Methods

The D-enantiomer peptide antagonists were modified and radiolabeled with ⁶⁸Ga. In vitro binding assays were performed in human peripheral blood mononuclear cells (PBMCs) to assess their affinity and specificity. The imaging capacity, biodistribution, pharmacokinetics, and radiation dosimetry were investigated. Flow cytometry, autoradiography, and immunohistochemical staining were used to confirm the expression of TIGIT. The safety and potential of ⁶⁸Ga-GP12 for PET/CT imaging of TIGIT expression were evaluated in NSCLC patients.

Results

⁶⁸Ga-labeled D-peptides were conveniently produced with high radiochemical yields, radiochemical purities and molar activities. In vitro binding assays demonstrated ⁶⁸Ga-GP12 has high affinity and specificity for TIGIT with a K_D of 37.28 nM. In vivo and ex vivo studies demonstrated the capacity of ⁶⁸Ga-GP12 for PET imaging of TIGIT expression with high tumor uptake of 4.22 ± 0.68 %ID/g and the tumor-to-muscle ratio of 12.94 ± 2.64 at 60 min post-injection. In NSCLC patients, primary and metastatic lesions found in ⁶⁸Ga-GP12 PET images were comparable to that in ¹⁸F-FDG PET images. Moreover, tracer uptake in primary and metastatic lesions and intra-tumoral distribution in the large tumor were inhomogenous, indicating the heterogeneity of TIGIT expression.

Conclusion

⁶⁸Ga-GP12 is a promising radiotracer for PET imaging of TIGIT expression in cancers, indicating its potential as a potential companion diagnostic for anti-TIGIT therapies.

SUBMITTER: Wang X

PROVIDER: S-EPMC8761874 | biostudies-literature |

REPOSITORIES: biostudies-literature

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