MAGNETICALLY DIRECTED POLY(LACTIC ACID) Y-90 MICROSPHERES - NOVEL AGENTS FOR TARGETED INTRACAVITARY RADIOTHERAPY

High energy beta-emitting radioisotopes like Yttrium-90 have a radioto xic range of about one centimeter. For cancer treatment they must be b rought near the tumor cells and kept there for as long as they are rad ioactive. We developed as carriers for the ionic form of Y-90 a matrix -type polymeric drug delivery system, poly(lactic acid) (PLA) microsph eres. This radiopharmaceutical could be selectively delivered to the t arget site after incorporating 10% Fe3O4 (magnetite) which made the ma gnetic microspheres (MMS) responsive to an external magnetic field. Fu rthermore, MMS are biodegradable and slowly hydrolyze into physiologic lactic acid after the radioactivity is completely decayed. Previously prepared 10-40 mu m MMS were radiochemically loaded to high specific activity with Y-90 at a pH of 5.7. Stability studies showed that appro ximately 95% of added Y-90 is retained within the PLA matrix after 28 days (>10 half-lives) at 37 degrees C in serum, and electron microscop y showed that the microspheres retained their characteristic morpholog ic appearance for the same time period. Cytotoxicity studies with SK-N -SH neuroblastoma cells growing in monolayer showed that the radiocyto toxicity of the microspheres could be directed magnetically to either kill or spare specific cell populations, thus making them of great int erest for targeted intracavitary tumor therapy. We are currently optim izing this system for use in the treatment of neoplastic meningitis. ( C) 1994 John Wiley and Sons, Inc.