Optical imaging in which photons are the information source seems to be a very important technique, less expensive and less harmful than more conventional diagnostic methods and suitable, for instance, for sensitive diagnosis capable of detecting cancer at an early stage. We have recently developed inorganic persistent luminescent nanoparticles (PLNPs) as nanoprobes useful for in vivo imaging that can master the difficulties of the biological environment such as tissue autofluorescence, absorption, or photobleaching because they are excited before injection into the animal. In this work, we have focused on silicate materials, CaMgSi2O6, that emit in the red/near-infrared range for several hours. With the aim of improving their luminescent properties and nanoparticle size, we have explored a new method of synthesis that allows a suitable yield of particles and studied the influence of chemical composition and crystalline structure on luminescence intensity. Adjusting the molar ratio of Ca/Mg/Si and crystallization temperature, very fine nanoparticles of PLNPs have been obtained with an improved luminescence and the high production yield necessary to promote the emergence of these nanoprobes in the field of optical imaging.