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Contemporary approaches for imaging skeletal metastasis

Bone Research 2015年第2期3卷 59-71页

作者： David Ulmert Lilja Solnes daniel lj thorek Program in Molecular Pharmacology and Chemistry Memorial Sloan Kettering Cancer Center Department of Surgery Sk?ne University Hospital Division of Nuclear Medicine Department of Radiology and Radiological Science Johns Hopkins University School of Medicine Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine

The skeleton is a common site of cancer metastasis. Notably high incidences of bone lesions are found for breast, prostate, and renal carcinoma. Malignant bone tumors result in significant patient morbidity. Identification of these lesions is a critical step to accurately stratify patients, guide treatment course, monitor disease progression, and evaluate response to therapy. Diagnosis of cancer in the skeleton typically relies on indirect bone-targeted radiotracer uptake at sites of active bone remodeling. In this manuscript, we discuss established and emerging tools and techniques for detection of bone lesions, quantification of skeletal tumor burden, and current clinical challenges.

关键词： bone Contemporary approaches for imaging skeletal metastasis

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In vivo radiometric analysis of glucose uptake and distribution in mouse bone

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Bone Research 2016年第1期4卷 31-38页

作者： Meredith L Zoch Diane S Abou Thomas L Clemens daniel lj thorek Ryan C Riddle Department of Orthopaedic Surgery Johns Hopkins University School of Medicine Baltimore USA Division of Nuclear Medicine an Molecular Imaging Department of Radiology and Radiological Science Johns Hopkins University School of Medicine Baltimore USA Baltimore Veterans Administration Medical Center Baltimore USA Department of Oncology Cancer Molecular and Functional Imaging Program Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore USA

Bone formation and remodeling occurs throughout life and requires the sustained activity of osteoblasts and osteoclasts, particularly during periods of rapid bone growth. Despite increasing evidence linking bone cell activity to global energy homeostasis, little is known about the relative energy requirements or substrate utilization of bone cells. In these studies, we measured the uptake and distribution of glucose in the skeleton in vivo using positron-emitting 18F-fluorodeoxyglucose （[lSF]-FDG） and non-invasive, high-resolution positron emission tomography/computed tomography （PE~/CT） imaging and ex vivo autoradiography. Assessment of [~SF]-FDG uptake demonstrated that relative to other tissues bone accumulated a significant fraction of the total dose of the glucose analog..Skeletal accumulation was greatest in young mice undergoing the rapid bone formation that characterizes early development. PET/CT imaging revealed that [lSF]-FDG uptake was greatest in the epiphyseal and metaphyseal regions of long bones, which accords with the increased osteoblast numbers and activity at this skeletal site. Insulin administration significantly increased skeletal accumulation of [lSF]-FDG, while uptake was reduced in mice lacking the insulin receptor specifically in osteoblasts or fed a high-fat diet. Our results indicated that the skeleton is a site of significant glucose uptake and that its consumption by bone cells is subject to regulation by insulin and disturbances in whole-body metabolism.

关键词： bone FDG

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Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone

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Bone Research 2018年第2期6卷 189-196页

作者： Julie E.Pickett John M.Thompson Agnieszka Sadowska Christine Tkaczyk Bret R.Sellman Andrea Minola Davide Corti Antonio Lanzavecchia Lloyd S.Miller daniel lj thorek Division of Nuclear Medicine and Molecular Imaging Department of Radiology and Radiological ScienceJohns Hopkins University School of MedicineGaithersburgMDUSA Department of Orthopaedic Surgery Johns Hopkins University School of MedicineBaltimoreMD 21205USA Department of Infectious Disease MedImmune LLCGaithersburgMDUSA Humabs Bio Med SA BellinzonaSwitzerland Institute for Research in Biomedicine Universitàdella Svizzera italianaBellinzonaSwitzerland Department of Dermatology Johns Hopkins University School of MedicineBaltimoreMD 21205USA Division of Infectious Disease Department of MedicineJohns Hopkins University School of MedicineBaltimoreMDUSA Cancer Molecular and Functional Imaging Program Department of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21205USA

Discriminating sterile inflammation from infection, especially in cases of aseptic loosening versus an actual prosthetic joint infection, is challenging and has significant treatment implications. Our goal was to evaluate a novel human monoclonal antibody（mAb） probe directed against the Gram-positive bacterial surface molecule lipoteichoic acid（LTA）. Specificity and affinity were assessed in vitro. We then radiolabeled the anti-LTA mAb and evaluated its effectiveness as a diagnostic imaging tool for detecting infection via immuno PET imaging in an in vivo mouse model of prosthetic joint infection（PJI）. In vitro and ex vivo binding of the anti-LTA mAb to pathogenic bacteria was measured with Octet, ELISA, and flow cytometry. The in vivo PJI mouse model was assessed using traditional imaging modalities, including positron emission tomography（PET） with [^（18）F]FDG and [^（18）F]Na F as well as X-ray computed tomography（CT）, before being evaluated with the zirconium-89-labeled antibody specific for LTA（[^（89）Zr]SAC55）.The anti-LTA mAb exhibited specific binding in vitro to LTA-expressing bacteria. Results from imaging showed that our model could reliably simulate infection at the surgical site by bioluminescent imaging, conventional PET tracer imaging, and bone morphological changes by CT. One day following injection of both the radiolabeled anti-LTA and isotype control antibodies, the anti-LTA antibody demonstrated significantly greater（P 〈 0.05） uptake at S. aureus-infected prosthesis sites over either the same antibody at sterile prosthesis sites or of control non-specific antibody at infected prosthesis sites. Taken together, the radiolabeled anti-LTA mAb, [^（89）Zr]SAC55, may serve as a valuable diagnostic molecular imaging probe to help distinguish between sterile inflammation and infection in the setting of PJI. Future studies are needed to determine whether these findings will translate to human PJI.

关键词： Zr Molecularly specific detection bacterial lipoteichoic acid diagnosis prosthetic infection bone LTA SAC PET FDG tracer

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