Disphosphate based hydrogel microspheres for targeted transarterial radioembolization and chemoembolization therapies

Area of Science:

• Biomedical Engineering
• Radiochemistry
• Oncology

Background:

• Transarterial radioembolization (TARE) is a key treatment for unresectable hepatocellular carcinoma (HCC).
• Existing radioactive ⁹⁰Y resin microspheres have limitations including isotope leakage and low specific activity, impacting safety and efficacy.
• Novel diphosphonate based hydrogel microspheres (DPMs) are proposed to overcome these challenges.

Purpose of the Study:

• To develop and evaluate novel diphosphonate based hydrogel microspheres (DPMs) for enhanced transarterial radioembolization (TARE) therapies.
• To leverage the strong chelating capability of diphosphonates for universal radiolabeling with therapeutic metal nuclides.
• To create a dual-modality platform combining TARE and transcatheter arterial chemoembolization (TACE) for improved HCC treatment.

Main Methods:

• DPMs were fabricated using microfluidic technology.
• Fabricated DPMs were radiolabeled with ¹⁷⁷Lu and loaded with doxorubicin (DOX).
• Physicochemical properties, radiostability, in vitro and in vivo therapeutic efficacy, and biosafety were evaluated in orthotopic HCC rabbit models.

Main Results:

• DPMs demonstrated high labeling efficiency (98.3%) and exceptional radiostability (>99% over 7 days).
• The porous structure of DPMs facilitated high drug loading and controlled release, suitable for TACE.
• The combined ¹⁷⁷Lu-DPMs@DOX platform showed remarkable therapeutic efficacy against HCC with no observed side effects.

Conclusions:

• Diphosphonate based hydrogel microspheres represent a significant advancement for precise and safe TARE.
• The developed ¹⁷⁷Lu-DPMs@DOX platform offers a potent dual-modality treatment for unresectable HCC.
• This approach holds promise for treating various challenging tumors requiring targeted therapies.