Scintigraphic evaluation of experimental chronic osteomyelitis

Abstract

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 (99mTc-methylene diphosphonate [MDP], 67Ga-citrate) or are laborious to prepare (111In-leukocytes). We evaluated the performance of 2 new radiopharmaceuticals, 99mTc-polyethyleneglycol (PEG) liposomes and 99mTc-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 99mTc-PEG liposomes, 99mTc-HYNIC-IgG, and 99mTc-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 111In-granulocytes or 67Ga-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: 99mTc-PEG liposomes and 99mTc-HYNIC-IgG correctly identified all 6 rabbits with osteomyelitis. 11In-granulocytes and 67Ga-citrate gave equivocal results in 1 infected rabbit. 99mTc-MDP missed 1 case of osteomyelitis. The uptake in the affected region did not differ significantly between the agents, although 99mTc-MDP tended to have higher values (MDP, 4.75 +/- 1.23 percentage injected dose per gram [%ID/g]; 67Ga, 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, 99mTc-PEG liposomes and 99mTc-HYNIC-IgG performed at least as well as 111In-granulocytes and 67Ga-citrate in the localization of chronic osteomyelitis. The ease of preparation, the better image quality, and the lower radiation dose suggest that 99mTc-PEG liposomes and 99mTc-HYNIC-IgG might be suitable alternatives for 67Ga-citrate and 111In-granulocytes in the scintigraphic evaluation of osteomyelitis.