Purpose: Beta-emitting yttrium-90 spheres serve as a staple agent for radioembolization; however, limitations include costlyproduction, shunting from hepatic to pulmonary circulation, and limited post-procedural visualization. Our group has previously described the production of Liposomes in Alginate Microsphere (LAMs) which may be loaded with either Tc-99m or Re-186. These microspheres have great implications toward radioembolization applications; however, we propose an improved modality for their production in which pH gradientliposomes are encapsulated in alginate microspheres and subsequentially radiolabeled after production.
Materials and Methods: In brief, pH gradient liposomes were manufactured and microencapsulated in alginate microspheres via ultrasonication atomization. Microsphere diameter was measured via light microscopy. Microspheres were subsequentially incubated with Re-186/Tc-99m-BMEDA complexand then washed to remove unencapsulated radionuclide.Re-186/Tc-99m-BMEDA complex was incubated with alginate microspheres (minus any liposomes) for direct comparison to LAMs using gamma imaging.Tc-LAMs were intra-arterially delivered to an ex vivo bovine kidney perfusion model to assess embolization. Blood pressure and flow rate of the kidney were recorded. Venous return was collected during microsphere delivery. 5 minute planar gamma image and SPECTwas obtained of the embolized kidney and venous return.
Results: LAMs were constructed with a mean diameter of 49.5um (STDV = 10.4um). Re-LAMs demonstrated a radiolabeling efficiency of 51% whereas alginate sphere with no liposomes retained 15% of dose.2ml of 2.98mCiTc-LAMs were subsequentially constructed for delivery to the ex vivo kidney.BP was approximately 110/50 with a flow rate of approximately 300ml/minupon perfusion.The full dose of spheres was nonselectively delivered to the kidney via 3Fr microcatheter. Gamma imaging of venous return demonstrated venousshunting of 3.7% of radioactivity. SPECT demonstrated high activity in the renal cortex with trace dose appreciated along the venous outflow tract.
Conclusion: Our novel method for radiolabeling LAMsafter production demonstrated success regarding radioactivity retention and embolization capabilities.The proposed method facilitates the manufacture of the LAMs by radiopharmacies, without sacrificing the stability and radioactive retention of the microspheres. Future steps involve optimizing radiolabeling efficiency and maximizing therapeutic dose.