Preparation, radiolabeling with 99mTc and 67Ga and biodistribution studies of albumin nanoparticles coated with polymers

Abstract

ObjectiveTo optimize radiolabeling with 99mTc and 67Ga of albumin nanoparticles coated with 4 differents synthetic polymers and to evaluate their stability in vivo and in vitro, as well as their biodistribution in vivo after intravenous administration. Material and methodsThe nanoparticles were prepared using albumin and NOTA-modified albumin by the desolvation met-hod and coated with 4 different polymers: HPMC, GMN2, GPM2 and GTM2. They were purified, lyophilized and characterized. Radiolabelling with 99mTc was performed with 74MBq of 99mTc sodium pertechnetate, previously reduced with and acid solution of tin chloride at different concentrations (0.003, 0.005, 0.007, 0.01, 0.05 and 0.1mg/ml) and at different times (5, 10, 15, 30 and 60min) and temperatures (room temperature, 40°C and 60°C). Radiolabelling with 67Ga was performed by incubation of the nanoparticles with 37MBq of 67gallium chloride (obtained from commercial gallium-67citrate) at different times (10 and 30min) and temperatures (room temperature, 30°C and 60°C), and posterior purification with microconcentrators. The radiochemical purity was evaluated by TLC. Stability studies of radiolabeled nanoparticles in physiological serum and blood plasma were performed. Biodistribution studies of nanoparticles coated with GPM2 polymer were carried out in Wistar rats after intravenous administration of the nanoparticles. Control animals were carried out with 99mTc sodium pertechnetate and 67Ga chloride. To do so, the animals were killed and activity in organs was measured in a gamma counter. Results99mTc labeling was carried out optimally with a tin concentration of 0.007mg/ml for the GPM2 nanoparticles and 0.005mg/ml for the rest of the formulations, with a radiolabelling time of 10min at room temperature. In the case of 67Ga the label was optimized at 30°C temperature and 30min of incubation. In both cases the radiochemical purity obtained was greater than 97%. The nanoparticles showed high stability in vitro after 48h of labeling (70% nanoparticles labeled with 99mTc and 90% those labeled with 67Ga). Biodistribution studies of nanoparticles 99mTc-GPM2 and 67Ga-NOTA-GPM2 showed a high accumulation of activity in the liver at 2 and 24h after intravenous administration. ConclusionThe labeling procedure with 99mTc and 67Ga of albumin and albumin modified with NOTA nanoparticles allows obtaining nanoparticles with high labeling yields and adequate in vitro stability, allowing their use for in vivo studies.