⁶⁴Cu/¹⁷⁷Lu-DOTA-diZD, a Small-Molecule-Based Theranostic Pair for Triple-Negative Breast Cancer

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Triple-negative breast cancer (TNBC) has a poor prognosis due to limited targeted therapies.
• Tumor growth relies on angiogenesis, presenting a target for therapeutic intervention.

Purpose of the Study:

• To develop and evaluate a novel angiogenic-receptor-targeted radionuclide therapy (TRT) for TNBC.
• To assess the theranostic potential of a vascular endothelial growth factor receptor (VEGFR)-targeted agent.

Main Methods:

• Synthesis and radiolabeling of a VEGFR-targeted agent (diZD) with ¹⁷⁷Lu (for therapy) and ⁶⁴Cu (for imaging) using DOTA chelation.
• Evaluation of the theranostic pair (⁶⁴Cu/¹⁷⁷Lu)-DOTA-diZD in a 4T1 TNBC mouse model.

Main Results:

• The ¹⁷⁷Lu-DOTA-diZD TRT significantly increased median survival in 4T1-bearing mice from 18 to 28 days compared to controls.
• ⁶⁴Cu/¹⁷⁷Lu-DOTA-diZD demonstrated theranostic potential for TNBC.
• Anti-PD1 immunotherapy showed a median survival of only 16 days in this model.

Conclusions:

• Small-molecule VEGFR-oriented TRT is a promising therapeutic strategy for "immunogenic cold" TNBC.
• Targeted radionuclide therapy offers a novel treatment avenue for TNBC, outperforming immunotherapy in this study.