99mTc-E-selectin binding peptide for imaging acute osteomyelitis in a novel rat model

Introduction In the present study, Tc-99m-radiolabelled E-selectin binding peptide (Tc-99m-IMP-178) was investigated for its potential to image acutem pyogenic osteomyelitis in a new animal model. Intraindividual comparisons were performed using an irrelevant peptide (Tc-99m-IMP-100) to demonstrate specificity. Methods An acute pyogenic osteomyelitis was induced by injecting 0.05 ml of 5% sodium morrhuate and 5 x 10(8) CFU of Staphylococcus aureus into the medullary cavity of the right tibia in 16 rats. Sixteen additional rats served as untreated controls. Whole-body imaging of pyogenic (n = 4) and untreated (n = 4) animals was performed continously during the first 8 h (12 MBq i.v. of 99mTc-IMP-178 and Tc-99m-IMP-100 for control), and one further single image was acquired after 16 h p.i. Tissue biodistribution studies were performed in 12 rats with an acute pyogenic osteomyelitis and in 12 untreated rats 1, 4 and 24 h after injection. Data of the histological/radiological and haematological investigations were obtained in all animals. Results Histopathologically, 15 of 16 treated rats (93%) developed an acute pyogenic osteomyelitis showing a major infiltration of the bone marrow by polymorphonuclear leukocytes as well as the formation of sequestra. Haematologically, the number of leukocytes increased by 100%, the lymphocytes by 11% and the granulocytes decreased by 39%. After i.v. injection, Tc-99m-IMP-178 rapidly cleared from the body resulting in good scintigraphic target-to-background (T/B) ratios. The highest uptake of the tracer in the pyogenic bone was observed at 60 min p.i. (0.43 +/-0.02% ID.g(-1) for Tc-99m-IMP-178 and 0.30 +/-0.02% ID.g(-1) for Tc-99m-IMP-100), resulting in a higher osteomyelitis-to-healthy collateral ratio with T/B of 2.40 +/-0.65 (Tc-99m-IMP-178) compared with 1.85 +/-0.48 (Tc-99m-IMP-100). No adverse reactions were seen after injection of 99mTc-IMP-178. Conclusions Tc-99m-IMP-178 allows imaging of an acute osteomyelitic lesions, presumably by interaction of Tc-99m-IMP-178 with activated upregulated vascular endothelium. ((C) 2001 Lippincott Williams & Wilkins).