AB0248 Evaluation of subcutaneously (SC) injected tc 99m tilmanocept localization in active rheumatoid arthritis (RA) subjects by planar and spect/ct

Graf, Jonathan; Abbruzzese, B.; Cope, Frederick O.; Behr, Spencer C.; Sanders, James; Kissling, Allison; Ralph, David; Shuping, Joanna; Blue, Michael; Hartings, Carley; Hershey, Rachael; Bailey, Hannah; Spaulding, Aaron; Haynam, Matthew; Ismail, Ahmad Faisal

doi:10.1136/annrheumdis-2018-eular.7533

Cited by 2 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Preliminary results demonstrated that subcutaneous administration of 99m Tc-tilmanocept specifically labelled macrophage-mediated inflammation in RA, but not in healthy control subjects. 49 These data suggest that 99m Tc-tilmanocept may be useful as an imaging tool in RA. It would be of great interest and impact to determine if in vivo imaging of macrophages with tilmanocept in patients with early immune-mediated arthritis could identify affected joints so that treatment could be initiated early to prevent permanent joint damage.…”

Section: Discussionmentioning

confidence: 87%

“…gov Identifier: NCT03938636). Preliminary results demonstrated that subcutaneous administration of 99m Tc‐tilmanocept specifically labelled macrophage‐mediated inflammation in RA, but not in healthy control subjects 49 . These data suggest that 99m Tc‐tilmanocept may be useful as an imaging tool in RA.…”

Section: Discussionmentioning

confidence: 96%

“…Even more important for the patient is that this study portends the application of γ-tilmanocept to RA staging as it relates to pathotypical histopathology for RA and drug specificity responsiveness of RA to the RA pathotype. [43][44][45][46][47][48][49] In recent patient evaluations, Lewis et al identified transcriptional subgroups in synovium linked to three distinct RA pathotypes: fibroblastic pauci-immune pathotype, macrophage-rich diffuse-myeloid pathotype, and a lympho-myeloid pathotype characterized by infiltration of lymphocytes and myeloid cells. 48,50 This is suggestive of divergent pathogenic pathways or activation disease states.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Cy3‐tilmanocept labeling of macrophages in joints of mice with antibody‐induced arthritis and synovium of human patients with rheumatoid arthritis

Toribio

Young

Schlesinger

et al. 2020

Journal Orthopaedic Research

View full text Add to dashboard Cite

γ-Tilmanocept (99m Tc-tilmanocept) is a receptor-directed, radiolabeled tracer that is FDA-approved for guiding sentinel lymph node biopsy. Tilmanocept binds the C-type lectin mannose receptor (MR, CD206) on macrophages. In this study, nonradioactive, fluorescently-labeled Cy3-tilmanocept was used to detect CD206 + mononuclear cells in the cartilage of mice with antibody-induced arthritis and in the synovial fluid and tissue of human subjects with rheumatoid arthritis (RA) for comparison with osteoarthritis (OA), and healthy volunteer (HV) controls. Murine arthritis was induced by injection of monoclonal anti-cartilage antibody followed by injection of Escherichia coli lipopolysaccharide. Post-arthritis development (7-11 days), the mice were injected intravenously with Cy3-tilmanocept followed by in vivo and ex vivo epifluorescence imaging. Twophoton imaging, immunofluorescence, and immunohistochemistry were used to identify articular and synovial macrophages (CD206, F4/80, and Cy3-tilmanocept binding) in murine tissues. Cy3-tilmanocept epifluorescence was present in arthritic knees and elbows of murine tissues; no radiographic changes were noted in the skeletons. However, inflammatory arthritic changes were apparent by histopathology and immunohistochemistry (F4/80), immunofluorescence (CD206) and Cy3-tilmanocept binding. In human RA synovial fluid, Cy3-tilmanocept staining correlated with CD206 + / CD16 + cells; negligible labeling was observed in OA samples. Cy3-tilmanocept colocalized with CD206 and staining was significantly higher in RA synovial tissue compared to OA or HV. Our results demonstrate that imaging with Cy3-tilmanocept can detect in vivo inflammatory, CD206 + macrophages in an early arthritis animal model and in human RA patients. These data establish a novel tool for preclinical research of early arthritis and have implications for early RA detection and monitoring of therapeutic efficacy in humans.

show abstract

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cy3‐tilmanocept labeling of macrophages in joints of mice with antibody‐induced arthritis and synovium of human patients with rheumatoid arthritis

Toribio

Young

Schlesinger

et al. 2020

Journal Orthopaedic Research

View full text Add to dashboard Cite

show abstract

“…[ 99m Tc]Tc-tilmanocept, which is a molecular marker for the mannose receptor CD206, has been utilised in lymphoscintigraphy in oncology (72,73) and also limited phase 1 studies in mapping atherosclerotic inflammation (74) and rheumatoid arthritis (75,76). Enhanced expression of CD206 in macrophages, particularly in lung and pleural tissue with caseating granuloma, has portended a poorer prognosis in patients with these lesions (77).…”

Section: Role In Imaging Tb Using Gamma Spect Agentsmentioning

confidence: 99%

Tuberculosis: Role of Nuclear Medicine and Molecular Imaging With Potential Impact of Neutrophil-Specific Tracers

Marakalala

Sathekge

2021

Front. Med.

View full text Add to dashboard Cite

With Tuberculosis (TB) affecting millions of people worldwide, novel imaging modalities and tools, particularly nuclear medicine and molecular imaging, have grown with greater interest to assess the biology of the tuberculous granuloma and evolution thereof. Much early work has been performed at the pre-clinical level using gamma single photon emission computed tomography (SPECT) agents exploiting certain characteristics of Mycobacterium tuberculosis (MTb). Both antituberculous SPECT and positron emission tomography (PET) agents have been utilised to characterise MTb. Other PET tracers have been utilised to help to characterise the biology of MTb (including Gallium-68-labelled radiopharmaceuticals). Of all the tracers, 2-[18F]FDG has been studied extensively over the last two decades in many aspects of the treatment paradigm of TB: at diagnosis, staging, response assessment, restaging, and in potentially predicting the outcome of patients with latent TB infection. Its lower specificity in being able to distinguish different inflammatory cell types in the granuloma has garnered interest in reviewing more specific agents that can portend prognostic implications in the management of MTb. With the neutrophil being a cell type that portends this poorer prognosis, imaging this cell type may be able to answer more accurately questions relating to the tuberculous granuloma transmissivity and may help in characterising patients who may be at risk of developing active TB. The formyl peptide receptor 1(FPR1) expressed by neutrophils is a key marker in this process and is a potential target to characterise these areas. The pre-clinical work regarding the role of radiolabelled N-cinnamoyl –F-(D) L – F – (D) –L F (cFLFLF) (which is an antagonist for FPR1) using Technetium 99m-labelled conjugates and more recently radiolabelled with Gallium-68 and Copper 64 is discussed. It is the hope that further work with this tracer may accelerate its potential to be utilised in responding to many of the current diagnostic dilemmas and challenges in TB management, thereby making the tracer a translatable option in routine clinical care.

show abstract

AB0248 Evaluation of subcutaneously (SC) injected tc 99m tilmanocept localization in active rheumatoid arthritis (RA) subjects by planar and spect/ct

Cited by 2 publications

References 0 publications

Cy3‐tilmanocept labeling of macrophages in joints of mice with antibody‐induced arthritis and synovium of human patients with rheumatoid arthritis

Cy3‐tilmanocept labeling of macrophages in joints of mice with antibody‐induced arthritis and synovium of human patients with rheumatoid arthritis

Tuberculosis: Role of Nuclear Medicine and Molecular Imaging With Potential Impact of Neutrophil-Specific Tracers

Contact Info

Product

Resources

About