[99mTc]-labelled interleukin-8 as a diagnostic tool compared to [18F]FDG and CT in an experimental porcine osteomyelitis model

Abstract

Osteomyelitis (OM) is an important cause of morbidity and sometimes mortality in children and adults. Long-term complications can be reduced when treatment is initiated in an early phase. The diagnostic gold standard is microbial examination of a biopsy and current non-invasive imaging methods are not always optimal. [¹¹¹In]-leukocyte scintigraphy is recommended for peripheral OM, but is time-consuming and not recommended in children. [¹⁸F]FDG PET/CT is recommended for vertebral OM in adults, but has the disadvantage of false positive findings and a relatively high radiation exposure; the latter is a problem in children. [^99mTc]-based tracers are consequently preferred in children. We, therefore, aimed to find a [^99mTc]-marked tracer with high specificity and sensitivity for early detection of OM. Suppurating inflammatory lesions like OM caused by Staphylococcus aureus (S. aureus) will attract large numbers of neutrophils and macrophages. A preliminary study has shown that [^99m Tc]-labelled IL8 may be a possible candidate for imaging of peripheral OM. We investigated [^99mTc]IL8 scintigraphy in a juvenile pig model of peripheral OM and compared it with [¹⁸F]FDG PET/CT. The pigs were experimentally inoculated with S. aureus to induce OM and scanned one week later. We also examined leukocyte count, serum CRP and IL8, as well as performed histopathological and microbiological investigations. [ ^99m Tc]IL8 was easily and relatively quickly prepared and was shown to be suitable for visualization of OM lesions in peripheral bones detecting 70% compared to a 100% sensitivity of [¹⁸F]FDG PET/CT. [ ^99m Tc]IL8 is a promising candidate for detection of OM in peripheral bones in children.

Keywords: Animal model; CT; PET; SPECT/CT; [18F]FDG; [99mTc]IL8; osteomyelitis; pig; porcine; scintigraphy; staphylococcus aureus; swine.

Figure 1

Mean serum concentration of CRP in µg/ml and error bars in pigs with OM (n=8) and without OM (n=2) measured before (white boxes), 6 days after (gray boxes) and 7 days after (black boxes) inoculation with S. aureus. The diference between day 0 and day 6 was statistically (P=0.014) significant for pigs with OM as well as between day 0 and day 7 (P=0.006). There was no statistical significans between day 6 and 7 (P=0.322) for the pigs with OM.

Figure 2

Histopathology, mid-sagittal section of right proximal phalanx from toe IV, pig 9. Osteomyelitis is seen in the metaphysis distal to the growth plate and penetration of the cortical bone by the infection. Sequesters (S) and neutrophils (N) forming an intramedullary abscess close to the growth plate. Bar 4.5 mm. Hematoxylin and Eosin. Insert, immunohistochemically stain for IL8 corresponding to the framed area, and showing large areas of positive cells, primarily neutrophils. Bar 0.54 mm. Below is seen a CT scan (A) and a fusion image of IL8 scintigraphy and CT (B) of the same lesion indicated by arrows.

Figure 3

MIPs are showing the biodistribution of [^99mTc]IL8 (A) and [¹⁸F]FDG (B) in pig 8 without OM. Above these is shown the immunohistochemically stain for IL8 in the lung (scalebar: 25 µm). There was detectable IL8 in the lung parenchyma in and close to macrophags.

Figure 4

The figure shows [^99mTc]IL8 uptake in pig 2 without OM (A) in atelectasis and edematous changes in the right caudal lung without pneumonia and (B) CT of the same lung. Immunohistochemically stain for IL8 showed no detectable IL8 in the lung parenchyma (not shown). R: Right site.

Figure 5

Left: [¹⁸F]FDG (maximal intensity projection (MIP), upper) and [^99mTc]IL8 (MIP lower) uptake in pig 4 with 3 osteomyelitis lesions in the right hind limb as indicated by arrows. Right: CT (bone window) of A: osteomyelitis in proximal tibia and fibula, and of B: osteomyelitis in the third metatarsal bone. All OM having formed sequesters and fistulous tracts. The lesions are marked with an arrow. To the right in the CTs is shown a size bar (5 cm).