New insights on the output of a commercial Technegas generator were proposed in order to optimize the generation of a radioactive nanosized aerosol for human inhalation studies. Parameters influencing Technegas generated aerosols (i.e. gaseous atmosphere, generation temperature and storage duration) were analyzed by a combination of size-fractionation and gamma-scintigraphy detection to determine the aerosol aerodynamic-related distributions. It was found that the total radioactivity per mass and number concentrations of aerosols was mostly influenced by the burn temperature, while the radiolabelling of particles was mostly driven by their surface area. Tc-99m labeled nanosized carbonaceous primary particles appear mainly to result from nucleation/condensation of the supersaturated vapor during the burning step, and then coalesce into larger particles due to coagulation processes during the residence time in the expansion chamber. We showed that the burn temperature and the aerosol residence time were the main parameters influencing the particle size distribution. Under optimized operating conditions, the amount of radiolabelled nanoparticles substantially increased since the radioactivity median aerodynamic diameter was reduced by half (250 nm-GSD of 2.5) compared with the standard operating conditions of the Technegas generator (450 nm-GSD of 3.4). (C) 2012 Elsevier Ltd. All rights reserved.