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Scintigraphic Evaluation of Experimental Chronic Osteomyelitis

Departments of Nuclear Medicine, Internal Medicine, Orthopedics, and Radiology, University Hospital Nijmegen, Nijmegen
Department of Orthopedics, University Medical Center Utrecht, Utrecht
Institute for Pharmaceutical Science, Utrecht University, Utrecht, The Netherlands

Correspondence: For correspondence or reprints contact: Wim J.G. Oyen, MD, Department of Nuclear Medicine, University Hospital Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.

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. ¹¹¹In-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.

Key Words: osteomyelitis • liposomes • immunoglobulin • granulocytes • white blood cells • ⁶⁷Ga • ^99mTc • ¹¹¹In • bone scintigraphy • imaging

This article has been cited by other articles:

				S. Gratz, H. J.J.M. Rennen, O. C. Boerman, W. J.G. Oyen, P. Mast, T. M. Behr, and F. H.M. Corstens 99mTc-HMPAO-Labeled Autologous Versus Heterologous Leukocytes for Imaging Infection J. Nucl. Med., July 1, 2002; 43(7): 918 - 924. [Abstract] [Full Text] [PDF]