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

Afzelius, Pia; Alstrup, Aage Kristian Olsen; Nielsen, Ole Lerberg; Nielsen, Karin Michaelsen; Jensen, Svend Borup

doi:10.3390/molecules25184329

Cited by 4 publications

(11 citation statements)

References 23 publications

(77 reference statements)

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“…Studies may utilize either mini-pigs or commercial pigs. Perhaps the most widely utilized model of porcine osteomyelitis is a hematogenous model ( 56 , 145 – 149 ). Alternative models include mandibular osteomyelitis ( 46 , 150 ), tibial implant-related osteomyelitis ( 151 – 154 ), and traumatic tibial osteomyelitis ( 155 ).…”

Section: Large Animal Modelsmentioning

confidence: 99%

“…Lesions of osteomyelitis were found primarily in the long bones, but also in the costochondral junctions of ribs ( 147 ). This model has been modified and is most frequently used by administering bacterial inoculums into the femoral artery ( 145 , 146 , 148 , 149 ). Femoral artery inoculation is reliable in inducing osteomyelitis localized to the injected limb.…”

Section: Large Animal Modelsmentioning

confidence: 99%

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Role of Animal Models to Advance Research of Bacterial Osteomyelitis

Billings

Anderson

2022

Front. Vet. Sci.

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Osteomyelitis is an inflammatory bone disease typically caused by infectious microorganisms, often bacteria, which causes progressive bone destruction and loss. The most common bacteria associated with chronic osteomyelitis is Staphylococcus aureus. The incidence of osteomyelitis in the United States is estimated to be upwards of 50,000 cases annually and places a significant burden upon the healthcare system. There are three general categories of osteomyelitis: hematogenous; secondary to spread from a contiguous focus of infection, often from trauma or implanted medical devices and materials; and secondary to vascular disease, often a result of diabetic foot ulcers. Independent of the route of infection, osteomyelitis is often challenging to diagnose and treat, and the effect on the patient's quality of life is significant. Therapy for osteomyelitis varies based on category and clinical variables in each case. Therapeutic strategies are typically reliant upon protracted antimicrobial therapy and surgical interventions. Therapy is most successful when intensive and initiated early, although infection may recur months to years later. Also, treatment is accompanied by risks such as systemic toxicity, selection for antimicrobial drug resistance from prolonged antimicrobial use, and loss of form or function of the affected area due to radical surgical debridement or implant removal. The challenges of diagnosis and successful treatment, as well as the negative impacts on patient's quality of life, exemplify the need for improved strategies to combat bacterial osteomyelitis. There are many in vitro and in vivo investigations aimed toward better understanding of the pathophysiology of bacterial osteomyelitis, as well as improved diagnostic and therapeutic strategies. Here, we review the role of animal models utilized for the study of bacterial osteomyelitis and their critically important role in understanding and improving the management of bacterial osteomyelitis.

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Section: Large Animal Modelsmentioning

confidence: 99%

Section: Large Animal Modelsmentioning

confidence: 99%

Role of Animal Models to Advance Research of Bacterial Osteomyelitis

Billings

Anderson

2022

Front. Vet. Sci.

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“…In the bone, the fluoride anions are exchanged with the hydroxyl groups in the hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ), forming fluorapatite (Ca 10 (PO 4 ) 6 F 2 ) [ 18 , 19 ]. Our porcine osteomyelitis project included pigs scanned with [ 18 F]NaF, but while bone growth zones in the juvenile pigs were very visible, osteomyelitis-specific uptake of this tracer was not seen [ 20 ].…”

Section: Established Radiotracers For Bone Infectionmentioning

confidence: 99%

“…Moreover, in vitro experiments suggested binding to an intracellular epitope, which may be the result of the tracer targeting the compromised cell membranes of dead bacteria [ 78 ]. Furthermore, both [ 68 Ga]Ga-DOTA-K-A9 and [ 68 Ga]Ga-DOTA-GSGK-A11 were tested in a pig model, the result being quite disappointing as no tracer accumulation was found in the sites of osteomyelitis [ 20 ].…”

Section: Newer Tracers Considered For Bone Infection Imagingmentioning

confidence: 99%

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Radiotracers for Bone Marrow Infection Imaging

et al. 2021

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Introduction: Radiotracers are widely used in medical imaging, using techniques of gamma-camera imaging (scintigraphy and SPECT) or positron emission tomography (PET). In bone marrow infection, there is no single routine test available that can detect infection with sufficiently high diagnostic accuracy. Here, we review radiotracers used for imaging of bone marrow infection, also known as osteomyelitis, with a focus on why these molecules are relevant for the task, based on their physiological uptake mechanisms. The review comprises [67Ga]Ga-citrate, radiolabelled leukocytes, radiolabelled nanocolloids (bone marrow) and radiolabelled phosphonates (bone structure), and [18F]FDG as established radiotracers for bone marrow infection imaging. Tracers that are under development or testing for this purpose include [68Ga]Ga-citrate, [18F]FDG, [18F]FDS and other non-glucose sugar analogues, [15O]water, [11C]methionine, [11C]donepezil, [99mTc]Tc-IL-8, [68Ga]Ga-Siglec-9, phage-display selected peptides, and the antimicrobial peptide [99mTc]Tc-UBI29-41 or [68Ga]Ga-NOTA-UBI29-41. Conclusion: Molecular radiotracers allow studies of physiological processes such as infection. None of the reviewed molecules are ideal for the imaging of infections, whether bone marrow or otherwise, but each can give information about a separate aspect such as physiology or biochemistry. Knowledge of uptake mechanisms, pitfalls, and challenges is useful in both the use and development of medically relevant radioactive tracers.

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