A Comparative 68Ga-Citrate and 68Ga-Chloride PET/CT Imaging of Staphylococcus aureus Osteomyelitis in the Rat Tibia

Abstract

There may be some differences in the in vivo behavior of ⁶⁸Ga-chloride and ⁶⁸Ga-citrate leading to different accumulation profiles. This study compared ⁶⁸Ga-citrate and ⁶⁸Ga-chloride PET/CT imaging under standardized experimental models. Methods. Diffuse Staphylococcus aureus tibial osteomyelitis and uncomplicated bone healing rat models were used (n = 32). Two weeks after surgery, PET/CT imaging was performed on consecutive days using ⁶⁸Ga-citrate or ⁶⁸Ga-chloride, and tissue accumulation was confirmed by ex vivo analysis. In addition, peripheral quantitative computed tomography and conventional radiography were performed. Osteomyelitis was verified by microbiological analysis and specimens were also processed for histomorphometry. Results. In PET/CT imaging, the SUV_max of ⁶⁸Ga-chloride and ⁶⁸Ga-citrate in the osteomyelitic tibias (3.6 ± 1.4 and 4.7 ± 1.5, resp.) were significantly higher (P = 0.0019 and P = 0.0020, resp.) than in the uncomplicated bone healing (2.7 ± 0.44 and 2.5 ± 0.49, resp.). In osteomyelitic tibias, the SUV_max of ⁶⁸Ga-citrate was significantly higher than the uptake of ⁶⁸Ga-chloride (P = 0.0017). In animals with uncomplicated bone healing, no difference in the SUV_max of ⁶⁸Ga-chloride or ⁶⁸Ga-citrate was seen in the operated tibias. Conclusions. This study further corroborates the use of ⁶⁸Ga-citrate for PET imaging of osteomyelitis.

Figure 1

Schematic illustration of experimental design and timing of performed analysis methods.

Figure 2

Histological sections of osteomyelitic (a) and control (b) rat tibias at 2 weeks after surgery. The osteomyelitic changes were characterised by a wide circumferential periosteal reaction, focally enlarged haversian canals filled with fragmented polymorphonuclear leukocytes and occasional microabscesses, and major infiltration of the bone marrow by polymorphonuclear leukocytes. In some cases, a devitalized bone fragment was seen in the unhealed cortical window. In the control animals, periosteal reaction was minimal and there was modest endosteal new bone close to the cortical defect, indicating healing of the cortical defect. Modified van Gieson stain at ×10 magnification.

Figure 3

Time-activity curves for ⁶⁸Ga-citrate and ⁶⁸Ga-chloride accumulation at the site of induced osteomyelitis in rat tibia as determined by in vivo PET/CT imaging. The line represents the mean value of two animals. The radioactivity concentration, expressed in SUV, has been decay-corrected to the time of injection.

Figure 4

Representative transaxial PET, CT, and combined PET/CT images of ⁶⁸Ga-citrate and ⁶⁸Ga-chloride accumulation at the site of induced osteomyelitis and healing bone-defects at 2 weeks after surgery. In each animal, the left tibia (on the right) underwent surgery for induction of infection or the creation of a surgical defect to represent uncomplicated bone healing, with the contralateral intact bone (on the left) serving as the control.

Figure 5

Quantification of ⁶⁸Ga-citrate and ⁶⁸Ga-chloride PET/CT imaging at 2 weeks after surgery. Bar graphs represent mean SUV_max values (±SD) (a) and SUV_max ratios, that is, operated bone-to-intact bone (b) (n = 8).