Despite great interest in the use of silica mesoporous nanoparticles (MSNs) in drug delivery little is known on their biological fate. Positron emission tomography (PET) studies of radiolabelled MSNs face a major difficulty due to the degradation of the MSNs during circulation as it is difficult to assign activity values to either the MSNs or their degradation products. Here, a PET study is conducted using two strategies of labelling. MSNs are either radiolabelled in the core by complexation with silanols from the MSNs with 89Zr, or on the MSN coating through attachment of 131I radiolabelled Lin-TT1 (AKRGARSTA), a homing peptide for targeting cancer tissue. Results from the biodistribution of MSNs with the two labels are compared, obtaining meanful information on the fate of MSNs. While MSNs accumulate in liver and spleen, MSN degradation products 89Zr or silicate bearing the radioisotope, are found in the bones and probably in lungs. A partial detachment of the peptide from the surface of the MSN is also observed. This work highlights the importance of choosing an appropriate labelling strategy for nanoparticles since core or surface labelling may result in different particle biodistribution if the labelled component degrades or the label detaches.