Affibody-based molecular probe Tc-(HE)Z for non-invasive HER2 detection in ovarian and breast cancer xenografts.

PURPOSE

This study aimed to assess the biodistribution and bioactivity of the affibody molecular probe Tc-(HE)Z, prepared by genetic recombination, and to investigate its potential for targeted human epidermal growth factor receptor 2 (HER2) imaging in SKOV3 ovarian cancer and MDA-MB-361 breast cancer xenografts.

METHODS

Affibody molecules were generated through genetic recombination. The radiochemical purity of the Tc-labeled HER2 affibody was determined using reverse phase high performance liquid chromatography (RP-HPLC). Evaluation of HER2 affinity in SKOV3 ovarian cancer cells and MDA-MB-361 breast cancer cells (HER2-positive) was conducted by calculating equilibrium dissociation constants. Biodistribution of the Tc-labeled affibody molecular probe was assessed in Balb/c mice bearing SKOV3 tumors. Tumor targeting specificity was evaluated in Balb/c mice using SKOV3, MDA-MB-361, and AT-3 (HER2-negative) xenografts.

RESULTS

Affibody (HE)Z, generated through recombinant gene expression, was successfully labeled with Tc, achieving a radiochemical purity of (96.0 ± 1.7)% ( = 3) as determined by RP-HPLC. This molecular probe exhibited specific binding to HER2-positive SKOV3 cells, demonstrating intense radioactive uptake. Biodistribution analysis showed rapid accumulation of Tc-(HE)Z in HER2-positive tumors post-administration, primarily clearing through the urinary system. Single-photon emission computed tomography imaging conducted 1-3 h after intravenous injection of Tc-(HE)Z into HER2-positive SKOV3 and MDA-MB-361 nude mouse models confirmed targeted uptake of the molecular probe by the tumors.

CONCLUSIONS

The molecular probe Tc-(HE)Z developed in this study effectively targets HER2 for imaging HER2-positive SKOV3 and MDA-MB-361 xenografts . It exhibits rapid blood clearance without evident toxic effects, suggesting its potential as a valuable marker for detecting HER2 expression in tumor cells.