A Supramolecular Approach for Liver Radioembolization

Area of Science:

• Nanotechnology
• Supramolecular Chemistry
• Radiopharmaceutical Therapy

Background:

• Hepatic radioembolization faces challenges due to discrepancies between diagnostic planning and therapeutic delivery.
• These discrepancies can lead to adverse events like pulmonary shunting.
• A pre-targeting strategy could bridge diagnostic imaging and therapeutic delivery for improved outcomes.

Purpose of the Study:

• To develop and evaluate a nanotechnology-based pre-targeting strategy for hepatic radioembolization.
• To utilize host-guest interactions between adamantane and cyclodextrin for targeted delivery.
• To link pre-interventional diagnostics directly to local therapy delivery.

Main Methods:

• Employed adamantane-functionalized macroaggregated albumin (MAA-Ad) as the guest component.
• Used β-cyclodextrin-containing polymers (PIBMA) as the host component, radiolabeled with technetium-99m (99mTc) and Cy5.
• Evaluated *in vivo* pre-targeting by comparing the accumulation of 99mTc-labeled PIBMA polymers after embolization with MAA-Ad versus control MAA.

Main Results:

• Demonstrated successful *in vivo* supramolecular complex formation between adamantane and cyclodextrin.
• Observed a ten-fold increase in the accumulation of 99mTc-Cy50.5CD10PIBMA39 in target organs (liver/lungs) when pre-targeted with MAA-Ad compared to control.
• Showcased that pre-targeting with MAA alone was less efficient than with MAA-Ad.

Conclusions:

• The *in vivo* distribution of cyclodextrin-functionalized polymers can be effectively guided by pre-administered adamantane-functionalized particles.
• This supramolecular host-guest interaction creates a direct link between diagnostic imaging (scout-scan) and therapeutic delivery.
• The developed nanotechnology pre-targeting strategy shows promise for enhancing the precision and safety of radioembolization therapies.