Radioactive polymeric microspheres as a novel embolic agent for radiological interventional therapy: A preliminary evaluation

Abstract

Interventional therapy is very important in current clinical applications. However, the lack of quantifiable embolic agents to affect the therapeutic effects negatively. In the present study, we sought to prepare a novel embolic agent, 99mTc-Konjac glucoman/Poly(lactide-co-glycolide)@Polyethyleneimine@Diethylenetriaminepentaacetic acid(KGM/PLGA@PEI@DTPA)microspheres, which can be located and quantified noninvasively to further evaluate its biological effects in animal models. The KGM/PLGA microspheres were prepared with water/oil/water double emulsion-solvent evaporation. Subsequently, the surface modification was performed with PEI and DTPA as a bifunctional chelator to label the microspheres with 99mTc. The in vitro stability of 99mTc-KGM/PLGA@PEI@DTPA was determined through instant thin layer chromatography, and the in vitro cytotoxicity of KGM/PLGA@PEI@DTPA was evaluated with CCK-8 assays. The location and quantitative calculation of 99mTc-KGM/PLGA@PEI@DTPA in vivo were evaluated in rabbits through SPECT/CT, and the in vivo toxicity was assayed in rabbits.The microspheres showed no toxicity in vitro and in vivo, andthe diameter of microsphere was about 82.5 ± 14.5 μm(range 60–120 μm). The 99mTc-KGM/PLGA@PEI@DTPA was stable in phosphate-buffered saline and 50% fetal bovine serum within 6 h. The Single-photon emission computed tomography/computed tomography(SPECT/CT) imaging and biodistribution results showed that microspheres were mainly distributed in the liver, kidney, and bladder, and excreted through the urinary system. And the dose of microspheres embolizing in the liver was approximately 2.54 mg, 50.79% of the total injection, an estimate calculated according to the gamma ray emission from 99mTc in SPECT/CT.Hence, the 99mTc-KGM/PLGA@PEI@DTPA may be as a quantitative embolic agent and provide potential clinical value for interventional therapy.