Efficacy of 99mTc-Labeled Ceftizoxime in the Diagnosis of Subclinical Infections Associated with Titanium Implants in Rats

Background: Metal implants are used frequently in orthopedic procedures and the occurrence of subclinical low-virulence infection is difficult to diagnose. The objective of this study was to examine the hypothesis that peri-prosthetic subclinical infections may be diagnosed effectively in a murine model system using scintigraphic imaging with Tc-99m-labeled ceftizoxime. Methods: A sample population of 3-mo old Wistar rats (mean weight 327g) was divided randomly into a control group (n=6), which received sterile implants, and an experimental group (n=6), which received implants contaminated with Staphylococcus aureus strain ATCC6538-P. Animals were anesthetized and femoral titanium implants were fixed beneath muscle tissue in left hind limbs. Three weeks after surgery, animals were injected with Tc-99m-ceftizoxime solution (62.9MBq) and scintigraphic images were obtained at 3.5 and 6.5h after tracer injection. Results: According to the scintigraphic images, the radiopharmaceutical showed affinity for the operated thigh areas of experimental animals but not for those of the control group. There was no difference between the control and experimental groups regarding the amount of radioactivity in the regions of interest measured at 3.5h after injection of radiolabeled antibiotic, but the between-group difference determined at 6.5h after treatment was statistically significant (p=0.026). Moreover, the level of radioactivity recorded in resected thigh tissues derived from experimental animals was greater than that of the control group (p=0.035). Conclusion: Tc-99m-ceftizoxime scintigraphy can localize preferentially periprosthetic-infected areas adjacent to metal implants in a murine model. Furthermore, the radiolabeled antibiotic appears to be capable of detecting alterations in the micro-environment close to the implant and of reaching the bacteria attached to the implant surface.