Comparison of autologous (111)In-leukocytes, (18)F-FDG, (11)C-methionine, (11)C-PK11195 and (68)Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous staphylococcus aureus osteomyelitis model

Abstract

The aim of this study was to compare (111)In-labeled leukocyte single-photon emission computed tomography (SPECT) and (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose (11)C-methionine, (11)C-PK11195 and (68)Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a sequential scan protocol with (18)F-FDG, (68)Ga-citrate, (11)C-methionine, (11)C-PK11195, (99m)Tc-Nanocoll and (111)In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis lesions, five lesions characterized as abscesses/cellulitis, arthritis in three joints and five enlarged lymph nodes. None of the tracers accumulated in joints with arthritis. By comparing the 10 infectious lesions, (18)F-FDG accumulated in nine, (111)In-leukocytes in eight, (11)C-methionine in six, (68)Ga-citrate in four and (11)C-PK11195 accumulated in only one lesion. Overall, (18)F-FDG PET was superior to (111)In-leukocyte SPECT in marking infectious and proliferative, i.e. hyperplastic, lesions. However, leukocyte SPECT was performed as early scans, approximately 6 h after injection of the leukocytes, to match the requirements of the 18 h long scan protocol. (11)C-methionine and possibly (68)Ga-citrate may be useful for diagnosis of soft issue lesions.

Keywords: Osteomyelitis; X-Ray computed; animal; domestic pigs; emission-computed; lnfection; lnflammation; models; positron-emission tomography; single-photon; staphylococcus aureus; sus scrofa; swine; tomography.

Figure 1

Gross pathology, CT and histopathology, pig 1, 2 and 4. (A) Small soft tissue abscess, approx. 1 cm in diameter, in the right pelvic limb, pig 1; compare to Figure 3A. (B) CT, transversal projection, of pelvis, pig 1; compare to Figure 3A. (C) Gross pathology of right metatarsus II, medial view, pig 4; the abscess peripheral to the bone has been opened and pus evacuated exposing necrotic metatarsus II bone and a pathological fracture along the growth plate in the distal part of the bone. (D) Cellulitis, i.e. grey-red edematous tissue, peripheral to right patella, pig 2; the cranial surface of patella is present in the lower right part of the picture. Haematoxylin and eosin (E) and Masson trichrome (F) staining (trichrome stains collagen blue) of the tissue bridging viable and necrotic bone components of the right distal metatarsus III, pig 1; fibroblasts (Fib) with collagen formation, mononuclear cells (Mono) and neutrophilic granulocytes (Neu); bar = 100 µm.

Figure 3

Scans of pelvic (hind) limbs and region, pig 1. A: Tracer accumulation is evident in the right hind limb in the distal metatarsus III (a), distal femur (b), femoral head and neck (c), and the small abscess in the cranio-medial thigh muscle region (d); compare accumulation “c” to Figure 1B and “d” to Figure 1A; the urinary bladder (in the center) has prominent ¹⁸F-FDG accumulation. B: Transversal projection; accumulation of tracer in osteolytic metatarsus III of the right hind limb (a). C: Transversal projection; accumulation of tracer in abscess peripheral to the osteolytic metatarsus III of the right hind limb (a).

Figure 2

Whole body ⁶⁸Ga-citrate PET, maximum intensity projection (MIP), pig 1. Physiological accumulation in the growth zones (metaphyses) of the bones.

Figure 4

Scans of pelvic (hind) limbs and region, PET and SPECT to the left, and CT fused images to the right, transversal projections, pig 4. Tracers have accumulated in lesions in the right side of the pig. Sphere-formed accumulations (a) with ¹⁸F-FDG (panel A), ⁶⁸Ga-citrate (panel B) and ¹¹C-methionine (panel C) outline the large, approx. 8 cm in diameter, subcutaneous located abscess; focal accumulation (b) with ¹⁸F-FDG (panel A), ¹¹C methionine (panel C) and ¹¹C-PK11195 (panel D) identifies the mammary lymph node, and focal accumulation (c) of ¹¹¹In-leukocytes (panel E) identify the abscess; with ⁶⁸Ga-citrate, the mammary lymph node is barely visible (d).