Evaluation of 99mTc labelled poly lactic acid microspheres for diagnostic radioembolization

Radioembolization is used in diagnostic imaging of the lungs and for radioembolization therapy of hepatic tumours. Presently, 99mTc labelled macroaggregates or microspheres of human serum albumin (HAM) are used for this purpose. Poly lactic acid (PLA) is biodegradable, like HAM, and, unlike HAM, is not a blood product. The aim of the present study was to evaluate the uptake and biodegradation of PLA microspheres in lungs. PLA (MW = 48720 Da) microspheres of 1.0-100 microm (mean = 39.5 microm) in diameter were prepared by solvent evaporation from methylene chloride. They were labelled with 99mTc by stannous chloride reduction at pH 3, with an efficiency of 98% and a stability of 96% at 24 h. For biodistribution studies, 15 mice were i.v. injected with 20 microCi 99mTc-PLA microspheres in 0.1 ml and sacrificed at 15 min, 1, 3, 6 and 24 h (three at each time point). All the organs were removed, weighed and counted against a standard prepared from 1/100 dilution of the injected radioactivity. Some mice were similarly injected and sacrificed at 30 min, 15 and 30 days. The lungs were removed and frozen, and 10 microm sections were obtained, stained with haemotoxylin and eosin and examined under a light microscope. Five rabbits were i.v. injected with 1 mCi of 99mTc-PLA microspheres. Scintigrams were obtained at various intervals up to 24 h. In mice, the lung uptake was significant at 30 min-1h post-injection. In rabbits, the lungs were the only organs visualized up to 24 h. Microscopic examination of tissue sections demonstrated slow biodegradation of PLA particles. In conclusion; (1) The high lung uptake obtained in mice and rabbits indicates the suitability of PLA microspheres for lung imaging, and (2) although the slow biodegradation rate might be a disadvantage in patients with lung disorders in diagnostic studies, it may be an advantage in therapeutic applications with radionuclides which have long physical half lives.