Scintigraphic Evaluation of Experimental Chronic Osteomyelitis

Assessment of disease activity and disease extent in chronic osteomyelitis remains a difficult diagnostic problem. Radiography is not particularly sensitive. Scintigraphic techniques can be more helpful, but the routinely available agents lack specificity ( 99m Tc-methylene diphosphonate [MDP], 67 Ga-citrate) or are laborious to prepare ( 111 In-leukocytes). We evaluated the performance of 2 new radiopharmaceuticals, 99m Tc-polyethyleneglycol (PEG) liposomes and 99m Tc-hydrazinonicotinamide (HYNIC)-immunoglobulin G (IgG), in an experimental model of chronic osteomyelitis. Methods: Chronic osteomyelitis was induced in rabbits by inserting S. aureus into the right reamed and washed femoral canal. The canal was closed with cement. A sham operation was performed on the left femur. Routine radiographs were obtained immediately after surgery and before scintigraphy. Four weeks after surgery, each rabbit was injected with 37 MBq 99m Tc-PEG liposomes, 99m Tc-HYNIC-IgG, and 99m Tc-MDP on 3 consecutive days and imaged up to 4 (MDP) or 22 (liposomes and IgG) h after injection. On day 4, rabbits received either 18 MBq 111 In-granulocytes or 67 Ga-citrate and were imaged up to 44 h after injection. Uptake in the infected femur was determined by drawing regions of interest. Ratios of infected-to-sham-operated femur were calculated. After the last image, the rabbits were killed, and the left and right femur were scored for microbiologic and histopathologic evidence of osteomyelitis. Results: 99m Tc-PEG liposomes and 99m Tc-HYNIC-IgG correctly identified all 6 rabbits with osteomyelitis. 111 In-granulocytes and 67 Ga-citrate gave equivocal results in 1 infected rabbit. 99m Tc-MDP missed 1 case of osteomyelitis. The uptake in the affected region did not differ significantly between the agents, although 99m Tc-MDP tended to have higher values (MDP, 4.75 ± 1.23 percentage injected dose per gram [%ID/g]; 67 Ga, 2.05 ± 0.54 %ID/g; granulocytes, 1.56 ± 0.83 %ID/g liposomes, 1.75 ± 0.76 %ID/g, and IgG, 1.96 ± 0.27 %ID/g). The ratios of infected-to-normal femur were also not significantly different for the respective radiopharmaceuticals. Radiography visualized only severe osteomyelitis. Conclusion: In this rabbit model, 99m Tc-PEG liposomes and 99m Tc-HYNIC-IgG performed at least as well as 111 In-granulocytes and 67 Ga-citrate in the localization of chronic osteomyelitis. The ease of preparation, the better image quality, and the lower radiation dose suggest that 99m Tc-PEG liposomes and 99m Tc-HYNIC-IgG might be suitable alternatives for 67 Ga-citrate and 111 In-granulocytes in the scintigraphic evaluation of osteomyelitis.