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.