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 sen sitive. Scintigraphic techniques can be more helpful, but the routinely ava ilable agents lack specificity (Tc-99m-methylene diphosphonate [MDP], Ga-67 -citrate) or are laborious to prepare (In-111-leukocytes). We evaluated the performance of 2 new radiopharmaceuticals, Tc-99m-polyethyleneglycol (PEG) liposomes and Tc-99m-hydrazinonicotinamide (HYNIC)-immunoglobulin G (IgG), in an experimental model of chronic osteomyelitis. Methods: Chronic osteom yelitis was induced in rabbits by inserting S. aureus into the right reamed and washed femoral canal. The canal was closed with cement. A sham operati on was performed on the left femur. Routine radiographs were obtained immed iately after surgery and before scintigraphy. Four weeks after surgery, eac h rabbit was injected with 37 MBq Tc-99m-PEG liposomes, Tc-99m-HYNIC-IgG, a nd Tc-99m-MDP On 3 consecutive days and imaged up to 4 (MDP) or 22 (liposom es and IgG) h after injection. On day 4, rabbits received either 18 MBq In- 111-granulocytes or Ga-67-citrate and were imaged up to 44 h after injectio n. Uptake in the infected femur was determined by drawing regions of intere st. Ratios of infected-to-sham-operated femur were calculated. After the la st image, the rabbits were killed, and the left and right femur were scored for microbiologic and histopathologic evidence of osteomyelitis. Results: Tc-99m-PEG liposomes and Tc-99m-HYNIC-IgG correctly identified all 6 rabbit s with osteomyelitis. In-111-granulocytes and Ga-67-citrate gave equivocal results in 1 infected rabbit. Tc-99m-MDP missed 1 case of osteomyelitis. Th e uptake in the affected region did not differ significantly between the ag ents, although Tc-99m-MDP tended to have higher values (MDP, 4.75 +/- 1.23 percentage injected dose per gram [%ID/g]; Ga-67, 2.05 +/- 0.54 %ID/g; gran ulocytes, 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 si gnificantly different for the respective radiopharmaceuticals. Radiography visualized only severe osteomyelitis. Conclusion: In this rabbit model, Tc- 99m-PEG liposomes and Tc-99m-HYNIC-IgG performed at least as well as In-111 -granulocytes and Ga-67-citrate in the localization of chronic osteomyeliti s. The ease of preparation, the better image quality, and the lower radiati on dose suggest that Tc-99m-PEG liposomes and Tc-99m-HYNIC-IgG might be sui table alternatives for Ga-67-citrate and In-111-granulocytes in the scintig raphic evaluation of osteomyelitis.