Necrosis targeted combinational theragnostic approach using radioiodinated Sennidin A in rodent tumor models

Area of Science:

• Oncology
• Nuclear Medicine
• Radiochemistry

Background:

• Residual cancer cells impede curative treatment, leading to tumor relapse.
• Tumor necrosis therapy (TNT) aims to eliminate residual tumor cells.
• Targeting necrotic tumor tissue is crucial for effective cancer treatment.

Purpose of the Study:

• To develop and evaluate a novel theragnostic approach combining a vascular disrupting agent with radioiodinated sennidin A (¹³¹I-SA) for enhanced tumor necrosis therapy.
• To assess the targeting and retention capabilities of ¹³¹I-SA in necrotic tumors.
• To investigate the synergistic effects of ¹³¹I-SA and combretastatin A4 phosphate (CA4P) on tumor growth and survival.

Main Methods:

• Radioiodination of sennidin A (SA) to create ¹³¹I-SA.
• Administration of the vascular disrupting agent combretastatin A4 phosphate (CA4P) to induce tumor necrosis.
• Evaluation of ¹³¹I-SA uptake and retention in necrotic tumors using SPECT-CT imaging.
• Assessment of tumor growth inhibition, tumor doubling time, and animal survival in response to combined therapy.

Main Results:

• Sennidin A (SA) demonstrated high uptake and prolonged retention in necrotic tumors with rapid clearance from non-targeted tissues.
• SPECT-CT imaging confirmed persistent ¹³¹I-SA accumulation in tumor hotspots.
• The combination of ¹³¹I-SA and CA4P significantly inhibited tumor growth and extended animal survival.
• The theragnostic approach showed potent tumoricidal effects through debulking and secondary cell cleansing.

Conclusions:

• ¹³¹I-SA effectively targets necrotic tumor regions, making it a suitable agent for tumor necrosis therapy.
• Combining ¹³¹I-SA with necrosis-inducing agents like CA4P offers a promising theragnostic strategy for solid malignancies.
• This approach facilitates primary tumor debulking followed by targeted irradiation of residual cells, leading to synergistic tumor destruction.