TY - JOUR A1 - Möckel, J. A1 - Brangsch, J. A1 - Reimann, C. A1 - Kaufmann, Jan Ole A1 - Sack, I. A1 - Mangarova, D. B. A1 - Kader, A. A1 - Taupitz, M. A1 - Adams, L. C. A1 - Keller, S. A1 - Ludwig, A. A1 - Hamm, B. A1 - Botnar, R. M. A1 - Makowski, M. R. T1 - Assessment of Albumin ECM Accumulation and Inflammation as Novel In Vivo Diagnostic Targets for Multi-Target MR Imaging N2 - Atherosclerosis is a progressive inflammatory vascular disease characterized by endothelial dysfunction and plaque burden. Extracellular matrix (ECM)-associated plasma proteins play an important role in disease development. Our magnetic resonance imaging (MRI) study investigates the feasibility of using two different molecular MRI probes for the simultaneous assessment of ECM-associated intraplaque albumin deposits caused by endothelial damage and progressive inflammation in atherosclerosis. Male apolipoprotein E-deficient (ApoE-/-)-mice were fed a high-fat diet (HFD) for 2 or 4 months. Another ApoE-/--group was treated with pravastatin and received a HFD for 4 months. T1- and T2*-weighted MRI was performed before and after albumin-specific MRI probe (gadofosveset) administration and a macrophage-specific contrast agent (ferumoxytol). Thereafter, laser ablation inductively coupled plasma mass spectrometry and histology were performed. With advancing atherosclerosis, albumin-based MRI signal enhancement and ferumoxytol-induced signal loss areas in T2*-weighted MRI increased. Significant correlations between contrast-to-noise-ratio (CNR) post-gadofosveset and albumin stain (R2 = 0.78, p < 0.05), and signal loss areas in T2*-weighted MRI with Perls’ Prussian blue stain (R2 = 0.83, p < 0.05) were observed. No interference of ferumoxytol with gadofosveset enhancement was detectable. Pravastatin led to decreased inflammation and intraplaque albumin. Multi-target MRI combining ferumoxytol and gadofosveset is a promising method to improve diagnosis and treatment monitoring in atherosclerosis. KW - Magnetic resonance imaging KW - MRI KW - Imaging KW - Human serum albumin KW - Extracellular matrix KW - Macrophages KW - Contrast agent KW - Atherosclerotic plaques KW - Gadofosveset KW - Aneurysm PY - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:b43-536725 VL - 10 IS - 10 SP - 1 EP - 16 PB - MDPI CY - Basel AN - OPUS4-53672 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Adams, L. C. A1 - Brangsch, J. A1 - Kaufmann, Jan Ole A1 - Mangarova, D. B. A1 - Moeckel, J. A1 - Kader, A. A1 - Buchholz, R. A1 - Karst, U. A1 - Botnar, R. M. A1 - Hamm, B. A1 - Makowski, M. R. A1 - Keller, S. T1 - Effect of Doxycycline on Survival in Abdominal Aortic Aneurysms in a Mouse Model N2 - Background. Currently, there is no reliable nonsurgical treatment for abdominal aortic aneurysm (AAA). This study, therefore, investigates if doxycycline reduces AAA growth and the number of rupture-related deaths in a murine ApoE−/− model of AAA and whether gadofosveset trisodium-based MRI differs between animals with and without doxycycline treatment. Methods. Nine ApoE−/− mice were implanted with osmotic minipumps continuously releasing angiotensin II and treated with doxycycline (30 mg/kg/d) in parallel. After four weeks, MRI was performed at 3T with a clinical dose of the albumin-binding probe gadofosveset (0.03 mmol/kg). Results were compared with previously published wild-type control animals and with previously studied ApoE−/− animals without doxycycline treatment. Differences in mortality were also investigated between these groups. Results. In a previous study, we found that approximately 25% of angiotensin II-infused ApoE−/− mice died, whereas in the present study, only one out of 9 angiotensin II-infused and doxycycline-treated ApoE−/− mice (11.1%) died within 4 weeks. Furthermore, doxycycline-treated ApoE−/− mice showed significantly lower contrast-to-noise (CNR) values in MRI compared to ApoE−/− mice without doxycycline treatment. In vivo measurements of relative signal enhancement (CNR) correlated significantly with ex vivo measurements of albumin staining (R2 = 0.58). In addition, a strong visual colocalization of albumin-positive areas in the fluorescence albumin staining with gadolinium distribution in LA-ICP-MS was shown. However, no significant difference in aneurysm size was observed after doxycycline treatment. Conclusion. The present experimental in vivo study suggests that doxycycline treatment may reduce rupture-related deaths in AAA by slowing endothelial damage without reversing aneurysm growth. KW - Ggadolinium KW - MRI KW - Magnetic resonance imaging KW - Osmotic minipumps KW - Tetracyclin KW - Antibiotics KW - Angiotensin II KW - LA-ICP-MS PY - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:b43-527015 SP - 9999847 PB - Hindawi CY - London AN - OPUS4-52701 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Kader, A. A1 - Brangsch, J. A1 - Kaufmann, Jan Ole A1 - Zhao, J. A1 - Mangarova, D. B. A1 - Moeckel, J. A1 - Adams, L. C. A1 - Sack, I. A1 - Taupitz, M. A1 - Hamm, B. A1 - Makowski, M. R. T1 - Molecular MR Imaging of Prostate Cancer N2 - This review summarizes recent developments regarding molecular imaging markers for magnetic resonance imaging (MRI) of prostate cancer (PCa). Currently, the clinical standard includes MR imaging using unspecific gadolinium-based contrast agents. Specific molecular probes for the diagnosis of PCa could improve the molecular characterization of the tumor in a non-invasive examination. Furthermore, molecular probes could enable targeted therapies to suppress tumor growth or reduce the tumor size. KW - Prostate cancer KW - Magnetic resonance imaging KW - Molecular imaging KW - Imaging KW - Molecular marker KW - Screening KW - MRI KW - Diagnosis PY - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:b43-519503 VL - 9 IS - 1 SP - 1 EP - 17 PB - MDPI CY - Basel AN - OPUS4-51950 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Kader, A. A1 - Brangsch, J. A1 - Reimann, C. A1 - Kaufmann, Jan Ole A1 - Mangarova, D. B. A1 - Moeckel, J. A1 - Adams, L. C. A1 - Zhao, J. A1 - Saatz, Jessica A1 - Traub, Heike A1 - Buchholz, R. A1 - Karst, U. A1 - Hamm, B. A1 - Makowski, M. R. T1 - Visualization and Quantification of the Extracellular Matrix in Prostate Cancer Using an Elastin Specific Molecular Probe N2 - One of the most commonly diagnosed cancers in men is prostate cancer (PCa). Understanding tumor progression can help diagnose and treat the disease at an early stage. Components of the extracellular matrix (ECM) play a key role in the development and progression of PCa. Elastin is an essential component of the ECM and constantly changes during tumor development. This article visualizes and quantifies elastin in magnetic resonance imaging (MRI) using a small molecule probe. Results were correlated with histological examinations. Using an elastin-specific molecular probe, we were able to make predictions about the cellular structure in relation to elastin and thus draw conclusions about the size of the tumor, with smaller tumors having a higher elastin content than larger tumors. Human prostate cancer (PCa) is a type of malignancy and one of the most frequently diagnosed cancers in men. Elastin is an important component of the extracellular matrix and is involved in the structure and organization of prostate tissue. The present study examined prostate cancer in a xenograft mouse model using an elastin-specific molecular probe for magnetic resonance molecular imaging. Two different tumor sizes (500 mm3 and 1000 mm3) were compared and analyzed by MRI in vivo and histologically and analytically ex vivo. The T1-weighted sequence was used in a clinical 3-T scanner to calculate the relative contrast enhancement before and after probe administration. Our results show that the use of an elastin-specific probe enables better discrimination between tumors and surrounding healthy tissue. Furthermore, specific binding of the probe to elastin fibers was confirmed by histological examination and laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS). Smaller tumors showed significantly higher signal intensity (p > 0.001), which correlates with the higher proportion of elastin fibers in the histological evaluation than in larger tumors. A strong correlation was seen between relative enhancement (RE) and Elastica–van Gieson staining (R2 = 0.88). RE was related to inductively coupled plasma–mass spectrometry data for Gd and showed a correlation (R2 = 0.78). Thus, molecular MRI could become a novel quantitative tool for the early evaluation and detection of PCa. KW - Magnetic resonance imaging KW - MRI KW - Molecular imaging KW - Cancer KW - LA-ICP-MS PY - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:b43-538410 VL - 10 IS - 11 SP - 1 EP - 14 PB - MDPI CY - Basel AN - OPUS4-53841 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -