Kinetic Modelling of [Ga-68]Ga-DOTA-Siglec-9 in Porcine Osteomyelitis and Soft Tissue Infections

Background: [Ga-68]Ga-DOTA-Siglec-9 is a positron emission tomography (PET) radioligand for vascular adhesion protein 1 (VAP-1), a protein involved in leukocyte trafficking. The tracer facilitates the imaging of inflammation and infection. Here, we studied the pharmacokinetic modelling of [Ga-68]Ga-DOTA-Siglec-9 in osteomyelitis and soft tissue infections in pigs. Methods: Eight pigs with osteomyelitis and soft tissue infections in the right hind limb were dynamically PET scanned for 60 min along with arterial blood sampling. The fraction of radioactivity in the blood accounted for by the parent tracer was evaluated with radio-high-performance liquid chromatography. One- and two-tissue compartment models were used for pharmacokinetic evaluation. Post-mortem soft tissue samples from one pig were analysed with anti-VAP-1 immunofluorescence. In each analysis, the animal's non-infected left hind limb was used as a control. Results: Tracer uptake was elevated in soft tissue infections but remained low in osteomyelitis. The kinetics of [Ga-68]Ga-DOTA-Siglec-9 followed a reversible 2-tissue compartment model. The tracer metabolized quickly; however, taking this into account, produced more ambiguous results. Infected soft tissue samples showed endothelial cell surface expression of the Siglec-9 receptor VAP-1. Conclusion: The kinetics of [Ga-68]Ga-DOTA-Siglec-9 uptake in porcine soft tissue infections are best described by the 2-tissue compartment model.</div

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

Contains fulltext : 219440.pdf (Publisher’s version ) (Closed access)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. [(111)In]-leukocyte scintigraphy is recommended for peripheral OM, but is time-consuming and not recommended in children. [(18)F]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. [(99m)Tc]-based tracers are consequently preferred in children. We, therefore, aimed to find a [(99m)Tc]-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 [(99m)Tc]IL8 scintigraphy in a juvenile pig model of peripheral OM and compared it with [(18)F]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 [(18)F]FDG PET/CT. [ (99m) Tc]IL8 is a promising candidate for detection of OM in peripheral bones in children

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

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. [(111)In]-leukocyte scintigraphy is recommended for peripheral OM, but is time-consuming and not recommended in children. [(18)F]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. [(99m)Tc]-based tracers are consequently preferred in children. We, therefore, aimed to find a [(99m)Tc]-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 [(99m)Tc]IL8 scintigraphy in a juvenile pig model of peripheral OM and compared it with [(18)F]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 [(18)F]FDG PET/CT. [ (99m) Tc]IL8 is a promising candidate for detection of OM in peripheral bones in children

Pollution threatens toothed whales

In their Report “Ancient convergent losses of Paraoxonase 1 yield potential risks for modern marine mammals” (10 August, p.591), W. K. Meyer et al. show that marine mammals are particularly vulnerable to adverse health effects from organophosphorus pesticide pollution. Unfortunately, this finding is just one example of an evolutionary deficiency that puts marine mammals at increased risk for modern-day pollution