O ften, in vivo bacterial biofilms are inadvertently undetected since viable bacteria are shed only periodically. This hampers diagnosis, which often requires puncture biopsy and/or surgery, with the associated cost, morbidity, and mortality. Staphylococcus aureus is one of the most frequent device-associated pathogens. In staphylococcal biofilms, bacterial cells are interconnected by different types of polymeric matrices, including, among others, those composed of polysaccharide intercellular adhesin (PIA), also known as [polymeric N-acetyl--(1,6)-glucosamine] (PNAG), or proteins such as Bap (1-7). Of these, PIA/PNAG matrices are particularly common in clinical isolates (2) and medical device-related biofilm infections by S. aureus (mainly methicillin-susceptible S. aureus [MSSA]) and Staphylococcus epidermidis (8, 9).Subcutaneous catheters have been successfully used in models that simulate natural device-related staphylococcal infections. However, with the use of nonsealed catheters in these models, the biofilm may be developed inside the catheter lumen, allowing only a partial interaction between bacteria and the immune system cells (10, 11).Although S. aureus biofilm infections have been widely characterized and quantified, especially in vitro, an experimental noninvasive model to assess biofilm infections by natural or genetically modified bacteria is still needed to monitor in vivo infection and treatment efficacy in preclinical studies. One of the most useful animal models developed so far requires the use of bioluminescent S. aureus bacteria genetically modified to contain lux genes (12, 13). The use of this method is particularly limited when infections are caused by nonbioluminescent bacteria or in longterm studies, in which loss of bioluminescence may occur (14).Positron emission tomography (PET) with [ 18 F]fluoro-deoxyglucose ([ 18 F]FDG), an in vivo nuclear medicine imaging technique requiring the administration of this glucose analog radiotracer, is being successfully applied in clinical infections, since this radiotracer is metabolized by many infectious and inflammatory cells (15). This technique has been proposed for early detection of different infectious processes (16) and also in combination with magnetic resonance imaging for clinical and biomedical research (17). The main advantages of PET over other imaging techniques are its high sensitivity and the possibility to perform quantitative measurements in the images generated. In animals, [18 F]FDGMicroPET has been used in different rabbit osteomyelitis models (18,19). The most recent one was performed to detect staphylococcal infections in bone and compare S. aureus and S. epidermidis infections (18).The aim of our study was to determine the utility of a noninvasive [18 F]FDG-MicroPET in vivo imaging technology, using a sealed-catheter mouse model, in order to assess in vivo infection differences between S. aureus biofilm-producing strains and to monitor as well the effect of antimicrobial treatment in longitudinal studies. Results regardi...