Safety and Tolerability of Topotecan-Eluting Radiopaque Microspheres for Hepatic Chemoembolization in a Rabbit...

Area of Science:

• Oncology
• Interventional Radiology
• Drug Delivery Systems

Background:

• Topotecan, a camptothecin analogue, offers potential advantages over irinotecan for transarterial chemoembolization (TACE) in treating hepatic colorectal metastases.
• These advantages include greater anti-neoplastic activity and independence from enzymatic activation.
• Radiopaque microspheres loaded with topotecan (ROMTOP) present a novel approach for targeted drug delivery in TACE.

Purpose of the Study:

• To evaluate the safety and tolerability of topotecan-loaded radiopaque microspheres (ROMTOP) administered via TACE in a rabbit model.
• To compare the in vitro elution profile of topotecan from ROMTOP with that of irinotecan from similar microspheres.

Main Methods:

• Topotecan was loaded into 70-150 µm radiopaque microspheres (DC Bead LUMI™) to a maximum capacity of 80 mg/mL.
• Six New Zealand White rabbits underwent hepatic TACE with ROMTOP under fluoroscopic guidance until angiographic stasis.
• Safety was assessed through liver function tests, complete blood counts, and necropsy up to 28 days post-TACE. In vitro elution studies were conducted using an open-loop flow-through system.

Main Results:

• The mean topotecan dose delivered was 1.99 mg/kg. Transient elevations in liver enzymes were observed post-embolization, resolving within two weeks.
• One rabbit experienced a fatal complication (pyloric duodenal perforation) potentially due to non-target embolization.
• In vitro elution of topotecan from ROMTOP was complete in 10 hours, significantly longer than the 3 hours for irinotecan-loaded microspheres.

Conclusions:

• Selective hepatic embolization with ROMTOP at a dose of 2 mg/kg was tolerated in rabbits.
• The prolonged in vitro elution of topotecan from ROMTOP compared to irinotecan suggests potential for sustained drug release and improved therapeutic efficacy in TACE.