Re-labeled GX1 dimer as a novel dual-functional probe targeting TGM2 for imaging and antiangiogenic therapy of gastric cancer.

Purpose: The GX1 peptide (CGNSNPKSC) can specifically bind to TGM2 and possesses the ability to target the blood vessels of gastric cancer. This study intends to develop an integrated dual-functional probe with higher affinity, specificity and targeting and to characterize it in vivo and in vitro.

Methods: The dimer and tetramer of GX1 were prepared using cross-linked PEG and labeled with Tc. The best targeting probe [PEG-(GX1)] was selected by gamma camera imaging in nude mouse models of gastric cancer. Re-PEG-(GX1) was prepared and characterized through cell binding analysis and competitive inhibition experiments, gamma camera imaging, MTT analysis and flow cytometry, BLI, immunohistochemistry, HE staining and biochemical analysis.

Results: PEG-(GX1) bound specifically to Co-HUVEC with higher affinity than GX1. Re-PEG-(GX1) had better ability to target gastric cancer in tumor-bearing nude mice and higher T/H ratios than Re-GX1. Re-PEG-(GX1) inhibited the growth of Co-HUVEC and induced apoptosis, and its effects were more robust than those of Re-GX1. BLI showed that Re-PEG-(GX1) inhibited tumor proliferation in vivo with a stronger effect than Re-GX1. Compared with Re-GX1, Re-PEG-(GX1) suppressed tumor angiogenesis and tumor cell proliferation and induced tumor cell apoptosis in vivo. The Re-PEG-(GX1) group did not cause visible changes in liver and kidney morphology and function in vivo.

Conclusion: The dimer of GX1 was synthesized by using cross-linked PEG, and then Re-PEG-(GX1) was prepared. This radiopharmaceutical played both diagnostic and therapeutic functions, and gamma camera imaging could be utilized to detect the distribution of drugs in vivo during treatment. Through a series of experiments in vitro and in vivo, the feasibility of the drug was confirmed, and these results laid the foundation for the subsequent development and application of GX1.