Heterobivalent Dual-Target Peptide for Integrin-α_vβ₃ and Neuropeptide Y Receptors on Breast Tumor

Area of Science:

• Oncology
• Radiopharmaceuticals
• Molecular Imaging

Background:

• Breast cancer exhibits heterogeneous receptor expression, necessitating multi-targeted imaging agents.
• Integrin αvβ3 and Neuropeptide Y receptor 1 (Y1R) are overexpressed in breast tumors, representing viable therapeutic targets.
• Developing dual-receptor targeting probes can enhance diagnostic accuracy and therapeutic efficacy.

Purpose of the Study:

• To develop and preclinically evaluate [99mTc]HYNIC-cRGDfk-NPY, a novel heterodimer peptide probe for dual-receptor targeting in breast cancer imaging.
• To assess the in vitro and in vivo performance of the probe in preclinical models.

Main Methods:

• Synthesis and radiolabeling of the heterodimer peptide [99mTc]HYNIC-cRGDfk-NPY.
• In vivo biodistribution studies in healthy female BALB/c mice.
• Small-animal SPECT/CT imaging and ex vivo biodistribution in female SCID mice bearing MCF-7 (estrogen receptor-positive) and MDA-MB-231 (triple-negative) breast tumors.
• Assessment of non-specific uptake using an excess of unlabeled tracer.

Main Results:

• The [99mTc]HYNIC-cRGDfk-NPY probe demonstrated significant uptake in both MCF-7 and MDA-MB-231 tumor models.
• In vivo tumor uptake percentages were 9.30 ± 3.25% for MCF-7 and 4.93 ± 1.01% for MDA-MB-231.
• Favorable tumor-to-muscle ratios were observed: 5.65 ± 0.94 for MCF-7 and 7.78 ± 3.20 for MDA-MB-231.
• The probe exhibited rapid blood clearance and predominantly renal excretion.

Conclusions:

• [99mTc]HYNIC-cRGDfk-NPY shows excellent potential as a dual-receptor-targeting imaging agent for breast cancer.
• The probe's favorable biodistribution profile, including rapid clearance and tumor uptake, supports its further development for clinical application.
• This dual-targeting strategy may improve the sensitivity and specificity of breast cancer detection.