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^99mTc-Interleukin-8 for Imaging Acute Osteomyelitis

Department of Nuclear Medicine and Section of Histomorphology, Orthopaedic Research Laboratory, University Medical Center Nijmegen, Nijmegen, The Netherlands

Early and accurate diagnosis of osteomyelitis remains a clinical problem. Acute osteomyelitis often occurs in infants and most often is located in the long bones. Radiologic images show changes only in advanced stages of disease. Scintigraphic imaging with ^99mTc-methylene diphosphonate (MDP), or bone scanning, is much more sensitive in detecting acute osteomyelitis but lacks specificity. We evaluated the performance of ^99mTc-interleukin-8 (IL-8) in an experimental model of acute osteomyelitis. Methods: Acute pyogenic osteomyelitis was induced in 10 rabbits by inserting sodium morrhuate and Staphylococcus aureus into the medullary cavity of the right femur. The cavity was closed with liquid cement. A sham operation was performed on the left femur. Routine radiographs were obtained just before scintigraphy. Ten days after surgery, the rabbits were divided into 2 groups of 5 animals, received an injection of either 18.5 MBq ¹¹¹In-granulocytes or 18.5 MBq ⁶⁷Ga-citrate, and were imaged both 24 h after injection and 48 h after injection. On day 12, the rabbits received either 18.5 MBq ^99mTc-MDP or 18.5 MBq ^99mTc-IL-8, and serial images were acquired at 0, 1, 2, 4, 8, 12, and 24 h after injection. Uptake in the infected femur was determined by drawing regions of interest. Ratios of infected femur (target) to sham-operated femur (background) (T/Bs) were calculated. After the final images were obtained, the rabbits were killed and the right femur was dissected and analyzed for microbiologic and histopathologic evidence of osteomyelitis. Results: Acute osteomyelitis developed in 8 of 10 rabbits. All imaging agents correctly detected the acute osteomyelitis in these animals. The extent of infection was optimally visualized with ⁶⁷Ga-citrate and delayed bone scanning, whereas diaphyseal photopenia was noted with both ^99mTc-IL-8 and ¹¹¹In-granulocytes. In 1 rabbit with osteomyelitis, imaging results were falsely negative with ¹¹¹In-granulocytes and falsely positive with ^99mTc-MDP. Quantitative analysis of the images revealed that the uptake in the infected region was highest with ⁶⁷Ga-citrate (4.9 ± 0.8 percentage injected dose [%ID]) and ^99mTc-MDP (4.7 ± 0.7 %ID), whereas the uptake in the infected area was significantly lower with ^99mTc-IL-8 (2.2 ± 0.2 %ID) and ¹¹¹In-granulocytes (0.8 ± 0.2 %ID) (P < 0.0042). In contrast, the T/Bs were significantly higher for ^99mTc-IL-8 (T/B, 6.2 ± 0.3 at 4 h after injection) than for ⁶⁷Ga-citrate, ^99mTc-MDP, and ¹¹¹In-granulocytes, which had ratios of 1.5 ± 0.4, 1.9 ± 0.2, and 1.4 ± 0.1, respectively (P < 0.0001). Radiography correctly revealed acute osteomyelitis in only 2 of 8 rabbits. Conclusion: In this rabbit model of osteomyelitis, ^99mTc-IL-8 clearly revealed the osteomyelitic lesion. Although the absolute uptake in the osteomyelitic area was significantly lower than that obtained with ^99mTc-MDP and ⁶⁷Ga-citrate, the T/Bs were significantly higher for ^99mTc-IL-8 because of fast background clearance. The ease of preparation, good image quality, and lower radiation burden suggest that ^99mTc-IL-8 may be a suitable imaging agent for the scintigraphic evaluation of acute osteomyelitis.

Key Words: acute osteomyelitis • interleukin-8 • imaging infection • technetium

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