Background: [68Ga]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 [68Ga]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 [68Ga]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 [68Ga]Ga-DOTA-Siglec-9 uptake in porcine soft tissue infections are best described by the 2-tissue compartment model.

https://www.mdpi.com/1420-3049/24/22/4094/pdf

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

Advanced Imaging for Detection of Foci of Infection in Staphylococcus aureus Bacteremia- Can a Scan Save Lives?

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.

/pdf/99mtc-labelled-interleukin-8-as-a-diagnostic-tool-compared-64o81ercw7.pdf

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

Background [18F]FDG Positron Emission Tomography cannot differentiate between sterile inflammation and infection. Therefore, we, aimed to develop more specific radiotracers fitted for differentiation between sterile and septic infection to improve the diagnostic accuracy. Consequently, the clinicians can refine the treatment of, for example, prosthesis-related infection. Methods: We examined different target points; Staphylococcus aureus biofilm (68Ga-labeled DOTA-K-A9 and DOTA-GSGK-A11), bone remodeling ([18F]NaF), bacterial cell membranes ([68Ga]Ga-Ubiquicidin), and leukocyte trafficking ([68Ga]Ga-DOTA-Siglec-9). We compared them to the well-known glucose metabolism marker [18F]FDG, in a well-established juvenile S. aureus induced osteomyelitis (OM) pig model. Results: [18F]FDG accumulated in the OM lesions seven days after bacterial inoculation, but disappointingly we were not able to identify any tracer accumulation in OM with any of the supposedly more specific tracers. Conclusion: These negative results are, however, relevant to report as they may save other research groups from conducting the same animal experiments and provide a platform for developing and evaluating other new potential tracers or protocol instead.

/pdf/attempts-to-target-staphylococcus-aureus-induced-1fgr6ph1cl.pdf

Attempts to Target Staphylococcus aureus Induced Osteomyelitis Bone Lesions in a Juvenile Pig Model by Using Radiotracers.

Pediatric nuclear medicine is evolving, and its practice patterns are uncertain. Knowledge of the current trends in pediatric nuclear medicine might be helpful to direct local decisions, including expectations for patient care, needs for capital acquisitions, and staffing recruitment strategies. To provide data regarding the current practice of pediatric nuclear medicine via a Society for Pediatric Radiology (SPR) membership survey. The SPR emailed our 25-question survey to all 1,847 SPR members in August 2018 and we accepted responses until April 2019. Questions focused on nuclear medicine staffing, positron emission tomography (PET) utilization, and radiotherapy availability. Respondents could indicate their affiliated hospital, which we used for data cataloguing only. Analysis of survey responses was blinded to reported institution. We analyzed response data using contingency tables. Independence testing between categorical variables based on proportions of physicians with additional nuclear medicine board certification was performed on a subset of questions regarding PET and therapy practices. Sixty-seven people from at least 29 hospitals responded to the survey, including all 10 of the 2018–2019 U.S. News & World Report best children’s hospitals. The majority (48/67, 71.6%) of respondents indicated that pediatric nuclear medicine examinations were interpreted in the pediatric radiology department by pediatric radiologists and that most physicians interpreting the exams (43/67, 64.2%) did not have subspecialty certification in nuclear medicine or nuclear radiology. Most facilities offered PET/CT (57/67, 85.1%); few offered PET/MRI (12/67, 17.9%). Most facilities offered radiotherapies (57/67, 85.1%) but at most of these facilities (30/57, 52.6%), fewer than half the physicians who cover nuclear medicine were approved to administer therapies. In the subset analyses based on proportion of physicians with additional nuclear medicine board certification, there were statistically significant differences between the groups in availability of PET/MRI, lutetium-177 dotatate therapy programs, and percentages of physicians approved to administer therapies. Pediatric nuclear medicine is largely practiced by pediatric radiologists without subspecialty certification. Staffing, PET practices and therapies vary among practices, in part associated with the number of radiologists with nuclear medicine board certification.

Current trends in pediatric nuclear medicine: a Society for Pediatric Radiology membership survey.

To examine parameters affecting the detection of osteomyelitis (OM) by [18F]FDG PET/CT and to reduce tracer activity in a pig model. [18F]FDG PET/CT is recommended for the diagnosis of OM in the axial skeleton of adults. In children, OM has a tendency to become chronic or recurrent, especially in low-income countries. Early diagnosis and initiation of therapy are therefore essential. We have previously demonstrated that [18F]FDG PET/CT is promising in juvenile Staphylococcus aureus (S. aureus) OM of peripheral bones in a pig model, not failing even small lesions. When using imaging in children, radiation exposure should be balanced against fast diagnostics in the individual case. Twenty juvenile pigs were inoculated with S. aureus. One week after inoculation, the pigs were [18F]FDG PET/CT scanned. PET list-mode acquired data of a subgroup were retrospectively processed in order to simulate and examine the image quality obtainable with an injected activity of 132 MBq, 44 MBq, 13.2 MBq, and 4.4 MBq, respectively. All lesions were detected by [18F]FDG PET and CT. Some lesions were very small (0.01 cm3), and others were larger (4.18 cm3). SUVmax was higher when sequesters (p = 0.023) and fistulas were formed (p < 0.0001). The simulated data demonstrated that it was possible to reduce the activity to 4.4 MBq without compromising image quality in pigs. [18F]FDG PET/CT localized even small OM lesions in peripheral bones. It was possible to reduce the injected activity considerably without compromising image quality, impacting the applicability of PET/CT in peripheral OM in children.

/pdf/an-untapped-potential-for-imaging-of-peripheral-1zgo21l2pw.pdf

An untapped potential for imaging of peripheral osteomyelitis in paediatrics using [18F]FDG PET/CT -the inference from a juvenile porcine model.

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An untapped potential for imaging of peripheral osteomyelitis in paediatrics using [18F]FDG PET/CT -the inference from a juvenile porcine model.