Lymph Nodes Draining Infections Investigated by PET and Immunohistochemistry in a Juvenile Porcine Model.

BACKGROUND: [18F]FDG and [11C]methionine accumulate in lymph nodes draining S. aureus -infected foci. The lymph nodes were characterized by weight, [11C]methionine- and [18F]FDG-positron emissions tomography (PET)/computed tomography (CT), and immunohistochemical (IHC)-staining. METHODS: 20 pigs inoculated with S. aureus into the right femoral artery were PET/CT-scanned with [18F]FDG, and nine of the pigs were additionally scanned with [11C]methionine. Mammary, medial iliac, and popliteal lymph nodes from the left and right hind limbs were weighed. IHC-staining for calculations of area fractions of Ki-67, L1, and IL-8 positive cells was done in mammary and popliteal lymph nodes from the nine pigs. RESULTS: The pigs developed one to six osteomyelitis foci. Some pigs developed contiguous infections of peri-osseous tissue and inoculation-site abscesses. Weights of mammary and medial iliac lymph nodes and their [18F]FDG maximum Standardized Uptake Values (SUVFDGmax) showed a significant increase in the inoculated limb compared to the left limb. Popliteal lymph node weight and their FDG uptake did not differ significantly between hind limbs. Area fractions of Ki-67 and IL-8 in the right mammary lymph nodes and SUVMetmax in the right popliteal lymph nodes were significantly increased compared with the left side. CONCLUSION: The PET-tracers [18F]FDG and [11C]methionine, and the IHC- markers Ki-67 and IL-8, but not L1, showed increased values in lymph nodes draining soft tissues infected with S. aureus. The increase in [11C]methionine may indicate a more acute lymph node response, whereas an increase in [18F]FDG may indicate a more chronic response.

Preclinical Testing of Radiopharmaceuticals for the Detection and Characterization of Osteomyelitis: Experiences from a Porcine Model.

The development of new and better radioactive tracers capable of detecting and characterizing osteomyelitis is an ongoing process, mainly because available tracers lack selectivity towards osteomyelitis. An integrated part of developing new tracers is the performance of in vivo tests using appropriate animal models. The available animal models for osteomyelitis are also far from ideal. Therefore, developing improved animal osteomyelitis models is as important as developing new radioactive tracers. We recently published a review on radioactive tracers. In this review, we only present and discuss osteomyelitis models. Three ethical aspects (3R) are essential when exposing experimental animals to infections. Thus, we should perform experiments in vitro rather than in vivo (Replacement), use as few animals as possible (Reduction), and impose as little pain on the animal as possible (Refinement). The gain for humans should by far exceed the disadvantages for the individual experimental animal. To this end, the translational value of animal experiments is crucial. We therefore need a robust and well-characterized animal model to evaluate new osteomyelitis tracers to be sure that unpredicted variation in the animal model does not lead to a misinterpretation of the tracer behavior. In this review, we focus on how the development of radioactive tracers relies heavily on the selection of a reliable animal model, and we base the discussions on our own experience with a porcine model.

Radiotracers for Bone Marrow Infection Imaging.

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.

Clinical relevance of 18F-FDG-PET/CT incidental findings.

INTRODUCTION: The use of positron emission tomography with 2-deoxy-2-18F-fluoro-D-glucose integrated with CT (18F-FDG-PET/CT) in oncology is common. Unexpected incidental findings are occasionally recognised and can represent clinically relevant lesions or conditions. This study aims to assess the occurrence, clinical significance and economic impact of incidental 18F-FDG-PET/CT findings. METHODS: PET/CT of 670 cancer patients was evaluated in consensus by two experienced specialists within nuclear medicine and radiology. Foci with an abnormally increased 18F-FDG uptake and/or CT changes not related to the patients` disease were reported. Thirty-five foci in 29 patients were assessed and their cost and impact on patient management were analysed with up to 32 months of follow-up. A supplementary literature review was conducted using PubMed, Embase and Web of Science and the results were compared with ours. RESULTS: A total of 28 foci (80%) were clinically relevant and elicited management or follow-up including four malignancies and 18 premalignant and six benign lesions. Seven foci were without pathology. The estimated additional cost was 1,984 US$ per focus. In the literature review, 642 of 1,090 foci (59%) were relevant, distributed as 270 malignancies, 166 premalignant and 206 benign lesions, whereas 448 foci were without pathology. CONCLUSIONS: Incidental 18F-FDG-PET/CT findings should be investigated despite the occurrence of false-positive findings, additional time consumption and cost as they may represent obscure malignancies and premalignant or benign conditions needing treatment. FUNDING: none. TRIAL REGISTRATION: not relevant.

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

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.

[99mTc]-labelled interleukin-8 as a diagnostic tool compared to [18F]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. [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.

Effects of Long-term Anesthesia, Blood Sampling, Transportation, and Infection Status on Hearts and Brains in Pigs Inoculated with Staphylococcus aureus and Used for Imaging Studies.

Laboratory animals are widely used in imaging studies, including infection, heart, and brain research. Compared with rodents, pigs are especially useful because of their large organ sizes, ability to tolerate long-term anesthesia, and substantial blood volume, which allows repeated blood sampling. These factors are particularly important in positron emission tomography studies of potential new radioactive tracers, because the scans often are prolonged; in addition, kinetic studies involving repeated blood sampling may be performed to establish the optimal scan time. However, protracted studies may affect the cardiovascular system, brain, and other organs. This raises the question of how to monitor and counteract the effects of longterm anesthesia in pigs in a typical experimental setting yet prevent introducing bias into the experiment. To address this question, we investigated the effects of long-term anesthesia (maximum, 18 h), repeated blood sampling (maximum of 20 mL blood per kilogram body weight), and road transportation (as long as 1.5 h between 2 imaging centers) on key variables of lung, heart, and brain function in the context of a well-established pig model of Staphylococcus aureus infection. Pulse rate, oxygen saturation, body temperature, arterial pressure of CO2, and urine production were stable during anesthesia for at least 16 h, whereas blood glucose slowly decreased. Hct and leukocyte count decreased due to repeated blood sampling. During road transportation, blood lactate levels increased 5 fold and arterial pressure of O2 decreased by 50%. Repeated CT scans, necropsy results, and histopathology findings documented progressive lung changes and acute cardiac necrosis. No lesions indicative of hypoxia were found in brain. The study data show that the typical monitoring parameters do not fully depict the cardiovascular state of pigs during prolonged anesthesia. We recommend streamlining experimental protocols for imaging studies in pigs to avoid organ pathology.

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

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.

Intermittent vacuum treatment with VacuMed does not improve peripheral artery disease or walking capacity in patients with intermittent claudication.

To assess distal blood pressures (BPs) in ankle and toe, walking capacity, intermittent claudication symptoms, physical activity and self-rated health after intermittent vacuum treatment (IVT) for peripheral artery disease (PAD). Forty-eight patients with PAD were randomised to either a control (C)-group with lifestyle changes or lifestyle changes in combination with VacuMed® treatment thrice weekly for 6 weeks. Ankle and toe BPs were measured before, after 6 weeks of intervention and after 6 weeks follow-up. Walking capacity, intermittent claudication symptoms, physical activity and self-rated health (Likert scale) were also assessed. The ankle to brachial index (ABI) and BPs in the ankle and toe decreased after 6 and 12 weeks in both groups with no difference between the groups. In the legs with the lowest ABI at baseline in each patient, there were no differences regarding ABI, BPs and toe-systolic BP index between the groups after either the intervention or the follow-up period. The BPs decreased in both groups. The walking distance and the time to pain were unchanged in the IVT-group and increased in the C-group after the follow-up period, but without any significant differences between the groups. The level of objectively tested physical activity and self-rated health remained unchanged throughout the study in both the IVT- and the C-group. There were no differences between the changes of the self-rated health data during the study period between the IVT- and the C-group. VacuMed® had no effect per se on distal blood pressures, walking capacity, intermittent claudication symptoms, physical activity and self-rated health.

Post Mortem Leukocyte Scintigraphy in Juvenile Pigs with Experimentally Induced Osteomyelitis.

We have previously demonstrated that 111In-labeled autologous leukocyte scintigraphy is able to detect osteomyelitis in living juvenile pigs. In animal research studies, it may well be an advantage if the animals could be scanned after euthanasia. Applying traditional scanning of living animals to euthanized animals will render anaesthesia unnecessary and be ideal for obtaining good and reliable scans for the correct interpretation of imaging afterwards, since the animals do not move. The autologous leukocytes of the pigs were collected, marked with 111In, and reinjected into the pigs and allowed for homing to the site of infections as usual while the pigs were alive. In this study, we demonstrate that it is possible to perform SPECT/CT with 111In-labelled autologous leukocytes almost 24 hrs after euthanasia with the same detectability of osteomyelitic lesions as in living pigs (78% versus 79%). The pigs in this study had exactly the same experimental conditions as the living pigs and were examined in parallel with the living pigs except for euthanasia prior to the leukocyte scan and that no PET/CT scans were performed.

Kinetic Modelling of Infection Tracers [18F]FDG, [68Ga]Ga-Citrate, [11C]Methionine, and [11C]Donepezil in a Porcine Osteomyelitis Model.

Introduction: Positron emission tomography (PET) is increasingly applied for infection imaging using [18F]FDG as tracer, but uptake is unspecific. The present study compares the kinetics of [18F]FDG and three other PET tracers with relevance for infection imaging. Methods: A juvenile porcine osteomyelitis model was used. Eleven pigs underwent PET/CT with 60-minute dynamic PET imaging of [18F]FDG, [68Ga]Ga-citrate, [11C]methionine, and/or [11C]donepezil, along with blood sampling. For infectious lesions, kinetic modelling with one- and two-tissue-compartment models was conducted for each tracer. Results: Irreversible uptake was found for [18F]FDG and [68Ga]Ga-citrate; reversible uptake was found for [11C]methionine (two-tissue model) and [11C]donepezil (one-tissue model). The uptake rate for [68Ga]Ga-citrate was slow and diffusion-limited. For the other tracers, the uptake rate was primarily determined by perfusion (flow-limited uptake). Net uptake rate for [18F]FDG and distribution volume for [11C]methionine were significantly higher for infectious lesions than for correspondingly noninfected tissue. For [11C]donepezil in pigs, labelled metabolite products appeared to be important for the analysis. Conclusions: The kinetics of the four studied tracers in infection was characterized. For clinical applications, [18F]FDG remains the first-choice PET tracer. [11C]methionine may have a potential for detecting soft tissue infections. [68Ga]Ga-citrate and [11C]donepezil were not found useful for imaging of osteomyelitis.

Dual-energy X-ray Absorptiometry of Both Hips Helps Appropriate Diagnosis of Low Bone Mineral Density and Osteoporosis.

Controversy still remains regarding the use of bilateral hip scanning when bone mineral density (BMD) is measured, and bilateral hip scanning is not mandatory in international guidelines for screening of osteoporosis. BMD of both hips and the lumbar spine was analyzed in 133 consecutive individuals. There were discrepancies between the lowest T-scores of both hips. Fourteen of the 133 participants (11%) were diagnosed with a poorer BMD status when the BMD of the hip of the dominant leg was analyzed. The total hip BMD of the dominant hip was lower than in the non-dominant hip, (p = 0.035), whereas there were no differences in the femoral neck area of the dominant and the non-dominant leg (p = 0.754). When classified by Z- or T-scores, there was consistency in 60 cases (45%) and inconsistency in 59 cases (44%). In 14 cases (11%), T- or Z-scores were the same, and it did not matter whether the non-dominant hip or the dominant hip had been chosen. A diagnostic discordance of 11% between the left and the right hip was observed when the lumbar spine was evaluated. The lowest Z- and T-scores of the hips were, in 44% of the cases, found in the hip of the assumed dominant leg. BMD measurements of both hips are recommended as clinical practice.

Blood perfusion in osteomyelitis studied with [15O]water PET in a juvenile porcine model.

BACKGROUND: Osteomyelitis is a serious disease which can be difficult to treat despite properly instituted antibiotic therapy. This appears to be related at least partly to degraded vascularisation in the osteomyelitic (OM) lesions. Studies of perfusion in OM bones are, however, few and not quantitative. Quantitative assessment of perfusion could aid in the selection of therapy. A non-invasive, quantitative way to study perfusion is dynamic [15O]water positron emission tomography (PET). We aim to demonstrate that the method can be used for measuring perfusion in OM lesions and hypothesize that perfusion will be less elevated in OM lesions than in soft tissue (ST) infection. The study comprised 11 juvenile pigs with haematogenous osteomyelitis induced by injection of Staphylococcus aureus into the right femoral artery 1 week before scanning (in one pig, 2 weeks). The pigs were dynamically PET scanned with [15O]water to quantify blood perfusion. OM lesions (N = 17) in long bones were studied, using the left limb as reference. ST lesions (N = 8) were studied similarly. RESULTS: Perfusion was quantitatively determined. Perfusion was elevated by a factor 1.5 in OM lesions and by a factor 6 in ST lesions. CONCLUSIONS: Blood perfusion was successfully determined in pathological subacute OM lesions; average perfusion was increased compared to that in a healthy bone, but as hypothesized, the increase was less than in ST lesions, indicating that the infected bone has less perfusion reserve than the infected soft tissue.

Sternocostoclavicular Hyperostosis: An Ill-Recognized Disease.

Sternocostoclavicular hyperostosis (SCCH) is an ill-recognized, rarely diagnosed disease. Today, SCCH is widely considered part of the synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome. SCCH develops over years with intermittent attacks of pain, swelling, and reddening of the sternocostoclavicular region. The disease causes progressive hyperostosis, fusion of the sternocostoclavicular joints, and soft tissue ossification. SCCH is chronic, non-malignant, and occurs predominantly bilaterally in middle-aged women. The incidence of the disease is unknown. We present a case of isolated SCCH, where chest radiographs showed a clear development of bilateral disease over the course of more than a decade. Whole-body bone scintigraphy was performed and was suggestive of SCCH. The diagnosis was established as late as 14 years from the onset of symptoms. During this period, the patient underwent several inconclusive examinations, resulting in a delay of diagnosis and in prolonged and aggravated symptoms. With this case report, we want to draw attention to SCCH and the importance of early diagnosis of the disease.

(68)Ga-labeled phage-display selected peptides as tracers for positron emission tomography imaging of Staphylococcus aureus biofilm-associated infections: Selection, radiolabelling and preliminary biological evaluation.

INTRODUCTION: Staphylococcus aureus is a major cause of skin and deep-sited infections, often associated with the formation of biofilms. Early diagnosis and initiated therapy is essential to prevent disease progression and to reduce complications that can be serious. Imaging techniques are helpful combining anatomical with functional data in order to describe and characterize site, extent and activity of the disease. The purpose of the study was to identify and (68)Ga-label peptides with affinity for S. aureus biofilm and evaluate their potential as bacteria-specific positron emission tomography (PET) imaging agents. METHODS: Phage-displayed dodecapeptides were selected using an in vitro grown S. aureus biofilm as target. One cyclic (A8) and two linear (A9, A11) dodecapeptides were custom synthesized with 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid (DOTA) conjugated via a lysine linker (K), and for A11 also a glycine-serine-glycine spacer (GSG). The (68)Ga-labeling of A8-K-DOTA, A9-K-DOTA, and A11-GSGK-DOTA were optimized and in vitro bacterial binding was evaluated for (68)Ga-A9-K-DOTA and (68)Ga-A11-GSGK-DOTA. Stability of (68)Ga-A9-K-DOTA was studied in vitro in human serum, while the in vivo plasma stability was analyzed in mice and pigs. Additionally, the whole-body distribution kinetics of (68)Ga-A9-K-DOTA was measured in vivo by PET imaging of pigs and ex vivo in excised mice tissues. RESULTS: The (68)Ga-A9-K-DOTA and (68)Ga-A11-GSGK-DOTA remained stable in product formulation, whereas (68)Ga-A8-K-DOTA was unstable. The S. aureus binding of (68)Ga-A11-GSGK-DOTA and (68)Ga-A9-K-DOTA was observed in vitro, though blocking of the binding was not possible by excess of cold peptide. The (68)Ga-A9-K-DOTA was degraded slowly in vitro, while the combined in vivo evaluation in pigs and mice showed a rapid blood clearance and renal excretion of the (68)Ga-A9-K-DOTA. CONCLUSION: The preliminary in vitro and in vivo studies of the phage-display S. aureus biofilm-selected (68)Ga-A9-K-DOTA showed desirable features for a novel bacteria-specific imaging agent, despite of relative fast blood degradation in vivo.

Paraneoplastic retinopathy associated with occult bladder cancer.

The aim was to report the first case of cancer-associated retinopathy (CAR) presenting before bladder cancer diagnosis. A 71-year-old woman with a history of bilateral vision loss underwent subsequent complete ophthalmic examination include a fluorescein angiography, full-field electroretinogram (ERG), serology including serum antibodies for CAR, and positron emission tomography-computed tomography (PET-CT) scan. The patient was diagnosed with bladder carcinoma revealed by PET-CT. Timely recognition of this entity may be crucial for an increased patient survival thus adult onset progressive photoreceptor dysfunction, confirmed by ERG, should alert to a possible remote effect of known or occult malignancy. In the latter, PET-CT may be exploited as a powerful diagnostic tool.

Biodistribution of the radionuclides (18)F-FDG, (11)C-methionine, (11)C-PK11195, and (68)Ga-citrate in domestic juvenile female pigs and morphological and molecular imaging of the tracers in hematogenously disseminated Staphylococcus aureus lesions.

Approximately 5-7% of acute-care patients suffer from bacteremia. Bacteremia may give rise to bacterial spread to different tissues. Conventional imaging procedures as X-ray, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and ultrasound are often first-line imaging methods for identification and localization of infection. These methods are, however, not always successful. Early identification and localization of infection is critical for the appropriate and timely selection of therapy. The aim of this study was thus; a head to head comparison of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve uncovering of infectious lesions in soft tissues. We chose (11)C-methionine, (11)C-PK11195, and (68)Ga-citrate as tracers and besides presenting their bio-distribution we validated their diagnostic utility in pigs with experimental bacterial infection. Four juvenile 14-15 weeks old female domestic pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of S. aureus using a sequential scanning protocol with (18)F-FDG, (11)C-methionine, (11)C-PK11195 and (68)Ga-citrate. This was followed by necropsy of the pigs consisting of gross pathology, histopathology and microbial examination. The pigs primarily developed lesions in lungs and neck muscles. (18)F-FDG had higher infection to background ratios and accumulated in most infectious foci caused by S. aureus, while (11)C-methionine and particularly (11)C-PK11195 and (68)Ga-citrate accumulated to a lesser extent in infectious foci. (18)F-FDG-uptake was seen in the areas of inflammatory cells and to a much lesser extent in reparative infiltration surrounding necrotic regions.

Utility of 11C-methionine and 11C-donepezil for imaging of Staphylococcus aureus induced osteomyelitis in a juvenile porcine model: comparison to autologous 111In-labelled leukocytes, 99m Tc-DPD, and 18F-FDG.

The aim of this study was to compare 11C-methionine and 11C-donepezil positron emission tomography (PET) with 111In-labeled leukocyte and 99m Tc-DPD (Tc-99m 3,3-diphosphono-1,2-propanedicarboxylic acid) single-photon emission computed tomography (SPECT), and 18F-fluorodeoxyglucose (18F-FDG) PET to improve detection of osteomyelitis. The tracers' diagnostic utility where tested in a juvenile porcine hematogenously induced osteomyelitis model comparable to osteomyelitis in children. Five 8-9 weeks old female domestic pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus. The sequential scan protocol included Computed Tomography, 11C-methionine and 11C-donepezil PET, 99m Tc-DPD and 111In-labelled leukocytes scintigraphy, and 18F-FDG PET. This was followed by necropsy of the pigs and gross pathology, histopathology, and microbial examination. The pigs developed a total of 24 osteomyelitic lesions, 4 lesions characterized as contiguous abscesses and pulmonary abscesses (in two pigs). By comparing the 24 osteomyelitic lesions, 18F-FDG accumulated in 100%, 111In-leukocytes in 79%, 11C-methionine in 79%, 11C-donepezil in 58%, and 99m Tc-DPD in none. Overall, 18F-FDG PET was superior to 111In-leukocyte SPECT and 11C-methionine in marking infectious lesions.