^99mTc-labeled peptide targeting interleukin 13 receptor α 2 for tumor imaging in a cervical cancer mouse model

Pep-1 (CGEMGWVRC) can potently bind to interleukin 13 receptor α 2 (IL-13Rα2), a tumor-restricted receptor found to be expressed in various malignancies. In this study, we intended to prepare a ^99mTc-labeled probe and evaluate its in vivo tumor accumulation properties in a cervical cancer xenograft model.

The Pep-1 was designed and radiolabeled with ^99mTc by conjugation with mercaptoacetyl-triglycine (MAG₃). The labeling yield, radiochemical purity and stability were characterized in vitro. Cell uptake assays and fluorescence imaging were conducted for qualitative and quantitative evaluation of the specificity and affinity of Pep-1. Flow cytometry and tissue immunofluorescence were used to confirm the IL-13Rα2 expression in cervical cancer. Biodistribution and in vivo imaging were performed periodically to evaluate the imaging value of ^99mTc-MAG₃-Pep-1 in cervical cancer xenograft model.

^99mTc-MAG₃-Pep-1 was successfully prepared with a high labeling yield and radiochemical purity (> 95%). Specific cell uptake was demonstrated by scramble control and unlabeled MAG₃-Pep-1 blockade. Flow cytometry and tissue immunofluorescence also confirmed the mild IL-13Rα2 expression of HeLa. In the gamma imaging study and biodistribution, the tumors were imaged clearly at 2-6 h after injection of ^99mTc-MAG₃-Pep-1 and the accumulation of ^99mTc-MAG₃-Pep-1 in tumor was significantly higher than that in the blocking and scramble controls, demonstrating ligand-receptor binding specificity.

This work demonstrated that ^99mTc-MAG₃-Pep-1 can bind to cervical cancer with high affinity and specificity. MAG₃-Pep-1 may be a prospective precursor for IL-13Rα2-expressing cancer therapy.