Development of Radiotherapeutic Rhenium-188 Liposomes in Alginate Microspheres (Rhe-Lams) for Treatment of Liver Tumors and Technetium-99M Liposomes in Alginate Microspheres (Tech-Lams) for Image-Guided Treatment Planning.

e15599 Background: Radio-embolic agents such as beta-emitting yttrium-90 spheres have been widely adopted as a modality for liver cancer therapy; however, their production can be timely and costly, shunting to the lungs may occur, and post-procedural visualization is limited. Alginate, a polysaccharide which can easily be formed into microspheres, has already been investigated for drug delivery applications; however, we propose utilizing alginate to manufacture radioembolic microspheres for intra-arterial delivery to liver tumors: Rhenium-188/186-labeled liposomes in alginate microspheres (Rhe-LAMS) as a radioembolic agent for the treatment of liver tumors and technetium-99m labeled liposomes in alginate microspheres (Tech-LAMs) as an agent for nuclear image-guided pre-treatment planning for liver cancer patients. Methods: Liposomes were manufactured and labeled with either Re-188/186 or Tc-99m. The liposomes were then mixed with alginate solution and then cross-linked with CaCl2 to form microspheres. Microsphere diameter was evaluated via light microscopy, and retention of radioactivity was measured over time via dosimeter. Microspheres containing free Re-186/Tc-99m (i.e. no liposomes) were also constructed for control comparison. To test in vivo stability, Tech-LAMs were intra-arterially injected into the liver of rabbits for nuclear imaging. Results: 2 ml batches of Rhe-LAMS/Tech-LAMS of 20-80 microns could be manufactured in 3 hours. Radiolabeling efficiency of the liposomes reached 85% and retention of radioactivity in microspheres reached 75%. After overnight incubation, 90% activity was retained. Control microspheres showed a retention of < 5%. In vivo imaging revealed absent activity in the lungs and high embolic activity in the liver. Conclusions: Our novel method demonstrated success regarding radioactivity retention and embolization capabilities. We envision this method to be a quickly-producible, cost-efficient, and effective means for radioembolization of liver tumors that could be adopted by any radiopharmacy.