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  1. Article ; Online: Shining Damaged Hearts

    David Kersting / Stephan Settelmeier / Ilektra-Antonia Mavroeidi / Ken Herrmann / Robert Seifert / Christoph Rischpler

    International Journal of Molecular Sciences, Vol 23, Iss 3802, p

    Immunotherapy-Related Cardiotoxicity in the Spotlight of Nuclear Cardiology

    2022  Volume 3802

    Abstract: The emerging use of immunotherapies in cancer treatment increases the risk of immunotherapy-related cardiotoxicity. In contrast to conventional chemotherapy, these novel therapies have expanded the forms and presentations of cardiovascular damage to a ... ...

    Abstract The emerging use of immunotherapies in cancer treatment increases the risk of immunotherapy-related cardiotoxicity. In contrast to conventional chemotherapy, these novel therapies have expanded the forms and presentations of cardiovascular damage to a broad spectrum from asymptomatic changes to fulminant short- and long-term complications in terms of cardiomyopathy, arrythmia, and vascular disease. In cancer patients and, particularly, cancer patients undergoing (immune-)therapy, cardio-oncological monitoring is a complex interplay between pretherapeutic risk assessment, identification of impending cardiotoxicity, and post-therapeutic surveillance. For these purposes, the cardio-oncologist can revert to a broad spectrum of nuclear cardiological diagnostic workup. The most promising commonly used nuclear medicine imaging techniques in relation to immunotherapy will be discussed in this review article with a special focus on the continuous development of highly specific molecular markers and steadily improving methods of image generation. The review closes with an outlook on possible new developments of molecular imaging and advanced image evaluation techniques in this exciting and increasingly growing field of immunotherapy-related cardiotoxicity.
    Keywords molecular imaging ; PET ; SPECT ; cardiotoxicity ; immunotherapy ; nuclear medicine ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Metabolic imaging with FDG-PET and time to progression in patients discontinuing immune-checkpoint inhibition for metastatic melanoma

    Justin Ferdinandus / Anne Zaremba / Lisa Zimmer / Lale Umutlu / Robert Seifert / Francesco Barbato / Selma Ugurel / Eleftheria Chorti / Viktor Grünwald / Ken Herrmann / Dirk Schadendorf / Wolfgang Peter Fendler / Elisabeth Livingstone

    Cancer Imaging, Vol 22, Iss 1, Pp 1-

    2022  Volume 8

    Abstract: Abstract Background The optimal duration of immune checkpoint blockade (ICB) therapy is not well established. Active residual disease is considered prohibitive for treatment discontinuation and its detection by diagnostic CT imaging is limited. Here, we ... ...

    Abstract Abstract Background The optimal duration of immune checkpoint blockade (ICB) therapy is not well established. Active residual disease is considered prohibitive for treatment discontinuation and its detection by diagnostic CT imaging is limited. Here, we set out to determine the potential added value of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) to identify patients at higher risk of relapse following discontinuation of ICB in advanced melanoma. Methods Metastatic melanoma patients who discontinued ICB were identified retrospectively. Eligible patients received FDG-PET and diagnostic CT within four months of ICB discontinuation. We defined morphologic response using RECIST v1.1. Complete metabolic response (CMR) was defined as uptake in tumor lesions below background, whereas any site of residual, FDG-avid disease was rated as non-CMR. The primary endpoint was time to progression (TTP) after therapy discontinuation stratified by morphologic and metabolic imaging response using Kaplan–Meier estimates and log-rank test. Results Thiry-eight patients were eligible for this analysis. Median follow-up was 37.3 months since ICB discontinuation. Median TTP in the overall cohort was not reached. A greater proportion of patients were rated as CMR in PET (n = 34, 89.5%) as compared to complete response (CR) in CT (n = 13, 34.2%). Median TTP was reached in patients with non-CMR (12.7 months, 95%CI 4.4-not reached) but not for patients with CMR (log-rank: p < 0.001). All patients with complete response by CT had CMR by PET. In a subset of patients excluding those with complete response by CT, TTP remained significantly different between CMR and non-CMR (log-rank: p < 0.001). Conclusion Additional FDG-PET at time of discontinuation of ICB therapy helps identify melanoma patients with a low risk of recurrence and favourable prognosis compared to CT imaging alone. Results may have clinical relevance especially for patients with residual tumor burden.
    Keywords Melanoma ; Immunotherapy ; Checkpoint inhibition ; PET ; FDG ; Discontinuation ; Medical physics. Medical radiology. Nuclear medicine ; R895-920 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Molecular imaging of MMP activity discriminates unstable from stable plaque phenotypes in shear-stress induced murine atherosclerosis.

    Robert Seifert / Michael T Kuhlmann / Sarah Eligehausen / Friedemann Kiefer / Sven Hermann / Michael Schäfers

    PLoS ONE, Vol 13, Iss 10, p e

    2018  Volume 0204305

    Abstract: PURPOSE:As atherosclerotic plaque ruptures are the primary cause of ischaemic events, their preventive identification by imaging remains a clinical challenge. Matrix metalloproteinases (MMP) are involved in plaque progression and destabilisation and are ... ...

    Abstract PURPOSE:As atherosclerotic plaque ruptures are the primary cause of ischaemic events, their preventive identification by imaging remains a clinical challenge. Matrix metalloproteinases (MMP) are involved in plaque progression and destabilisation and are therefore promising targets to characterize rupture-prone unstable plaques. This study aims at evaluating MMP imaging to discriminate unstable from stable plaque phenotypes. METHODS:ApoE deficient mice (ApoE-/-) on a high cholesterol diet underwent implantation of a tapered cuff around the right common carotid artery (CCA) inducing a highly inflamed atherosclerotic plaque upstream (US) and a more stable plaque phenotype downstream (DS) of the cuff. 8 weeks after surgery, the MMP inhibitor-based photoprobe Cy5.5-AF443 was administered i.v. 3h prior to in situ and ex vivo fluorescence reflectance imaging of the CCAs. Thereafter, CCAs were analysed regarding plaque size, presence of macrophages, and MMP-2 and MMP-9 concentrations by immunohistochemistry and ELISA. RESULTS:We found a significantly higher uptake of Cy5.5-AF443 in US as compared to DS plaques in situ (1.29 vs. 1.06 plaque-to-background ratio; p<0.001), which was confirmed by ex vivo measurements. Immunohistochemistry revealed a higher presence of macrophages, MMP-2 and MMP-9 in US compared to DS plaques. Accordingly, MMP-2 concentrations were significantly higher in US plaques (47.2±7.6 vs. 29.6±4.6 ng/mg; p<0.05). CONCLUSIONS:In the ApoE-/- cuff model MMP-2 and MMP-9 activities are significantly higher in upstream low shear stress-induced unstable atherosclerotic plaques as compared to downstream more stable plaque phenotypes. MMP inhibitor-based fluorescence molecular imaging allows visualization of these differences in shear stress-induced atherosclerosis.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616 ; 500
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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